Association of Ultraprocessed Foods Intake with Untargeted Metabolomics Profiles in Adolescents and Young Adults in the DONALD Cohort Study.

Background: High consumption of ultraprocessed foods (UPFs) continues to draw significant public health interest because of the associated negative health outcomes. Metabolomics can contribute to the understanding of the biological mechanisms through which UPFs may influence health.

Objectives: To investigate urine and plasma metabolomic biomarkers of UPF intake in adolescents and young adults.

Fludrocortisone dose-response relationship in septic shock: a randomised phase II trial.

Background: The combination of intravenous hydrocortisone and enteral fludrocortisone may reduce mortality in patients with septic shock. The optimal dose and reliability of absorption of fludrocortisone in critically ill patients are unclear.

Methods: In a multi-centre, open label, phase II randomized clinical trial, intravenous hydrocortisone alone or in combination with one of three doses of enteral fludrocortisone (50 µg, 100 µg or 200 µg daily) for 7 days was compared in patients with septic shock.

Myddosomes in Toll-like receptor signaling-one to bind and rule them all.

Toll-like receptors (TLRs) are innate immune sensors for the presence of pathogens and endogenous danger signals. TLR activation results in conserved intracellular signaling events that orchestrate inflammation and antimicrobial defense. While the identity and interplay of key TLR signaling components are well established, how these largely cytosolic proteins are physically connected is not well understood.

Socioeconomic risk and the longitudinal child lifetime prevalence of child protection involvement.

Background: North American studies find that geographic indicators of disadvantage, such as concentrated poverty, significantly increase the risk of child protection involvement. Despite having one of the most extensive family support systems and progressive income redistribution policies in North America, the Canadian province of Québec still faces geographic variations in socioeconomic conditions that remain a major risk factor for child protection involvement.

Objective: This study asks how child protection involvement is distributed across socioeconomically distinct geographic areas of the province.

Understanding the structure of autobiographical memories: A study of trauma memories from the 1994 Rwandan genocide.

How do we remember traumatic events, and are these memories different in individuals who experience post-traumatic stress? Some evidence suggests that traumatic events are mnemonically enhanced, or include more episodic detail, relative to other types of memories. Simultaneously, individuals with post-traumatic stress disorder (PTSD) have more non-episodic details in all of their memories, a pattern hypothesized to result from impairment in executive function. Here, we explore these questions in a unique population that experienced severely traumatic events more than 20 years ago - individuals who lived through the 1994 genocide in Rwanda.

Host gene expression signatures to identify infection type and organ dysfunction in children evaluated for sepsis: a multicentre cohort study.

Background: Sepsis is defined as dysregulated host response to infection that leads to life-threatening organ dysfunction. Biomarkers characterising the dysregulated host response in sepsis are lacking. We aimed to develop host gene expression signatures to predict organ dysfunction in children with bacterial or viral infection.

The habitat quality paradox: loss of riparian forest cover leads to decreased risk of parasitism and improved body condition in an imperiled amphibian.

Amphibian declines are a global phenomenon but responses of populations to specific threats are often context dependent and mediated by individual physiological condition. Habitat degradation due to reduced riparian forest cover and parasitism are two threats facing the hellbender salamander (), but their potential to interact in nature remains largely unexplored. We investigated associations between forest cover, parasitic infection and physiology of hellbenders to test the hypotheses that physiological condition responds to infection and/or habitat degradation.

Statistical analysis plan for the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial.

The NITric oxide during cardiopulmonary bypass (CPB) to improve Recovery in Infants with Congenital heart defects (NITRIC) trial, a 1320-patient, multicentre, randomised controlled trial, is aiming to improve survival free of ventilation after CPB by using nitric oxide delivered into the oxygenator of the CPB. To provide a statistical analysis plan before completion of patient recruitment and data monitoring. Final analyses for this study will adhere to this statistical analysis plan, which details all key pre-planned analyses.

Wollamide Cyclic Hexapeptides Synergize with Established and New Tuberculosis Antibiotics in Targeting Mycobacterium tuberculosis.

Shorter and more effective treatment regimens as well as new drugs are urgent priorities for reducing the immense global burden of tuberculosis (TB). As treatment of TB currently requires multiple antibiotics with diverse mechanisms of action, any new drug lead requires assessment of potential interactions with existing TB antibiotics. We previously described the discovery of wollamides, a new class of -derived cyclic hexapeptides with antimycobacterial activity.

Hippocampus long-axis specialization throughout development: A meta-analysis.

The human adult hippocampus can be subdivided into the head, or anterior hippocampus and its body and tail, or posterior hippocampus, and a wealth of functional differences along the longitudinal axis have been reported. One line of literature emphasizes specialization for different aspects of cognition, whereas another emphasizes the unique role of the anterior hippocampus in emotional processing. While some research suggests that functional differences in memory between the anterior and posterior hippocampus appear early in development, it remains unclear whether this is also the case for functional differences in emotion processing.

Nitric Oxide on Extracorporeal Membrane Oxygenation in Neonates and Children (NECTAR Trial): Protocol for a Randomized Controlled Trial.

Background: Extracorporeal membrane oxygenation (ECMO) provides support for the pulmonary or cardiovascular function of children in whom the predicted mortality risk remains very high. The inevitable host inflammatory response and activation of the coagulation cascade due to the extracorporeal circuit contribute to additional morbidity and mortality in these patients. Mixing nitric oxide (NO) into the sweep gas of ECMO circuits may reduce the inflammatory and coagulation cascade activation during ECMO support.

Immunity against Moraxella catarrhalis requires guanylate-binding proteins and caspase-11-NLRP3 inflammasomes.

Moraxella catarrhalis is an important human respiratory pathogen and a major causative agent of otitis media and chronic obstructive pulmonary disease. Toll-like receptors contribute to, but cannot fully account for, the complexity of the immune response seen in M. catarrhalis infection.

A bad time for kids in lockdown: The relationship between negative pandemic events, parenting stress, and maltreatment related parenting behaviors.

Background: To date, several studies have shown that parenting stress, a kind of role strain, is related to child maltreatment. However, few studies have examined how the effects of crises, such as negative pandemic-related events on the household, may be related to parenting stress and maltreatment-related behavior.

Objective: This study examines the impact of negative Covid-related events on parenting stress and parenting behaviors during a period that was likely to have been a peak point of stress for many parents during the Covid-19 pandemic.

Childhood Prevalence of Involvement with the Child Protection System in Quebec: A Longitudinal Study.

The goal of this study, the first of its kind in Canada, was to estimate the child lifetime prevalence of child protection involvement in Quebec. Using administrative and population data spanning 17 years, we performed a survival analysis of initial incidents of child protection reports, confirmed reports, confirmation of a child's security or development being compromised, and placement outside the home for one day or more. We found that before reaching the age of 18 years, over 18% of children were reported to child protection at least once, one in every ten children (10.

Distinct contributions of the innate immune receptors TLR2 and RP105 to formation and architecture of structured lung granulomas in mice infected with Mycobacterium tuberculosis.

Granulomas are key histopathological features of Mycobacterium tuberculosis (Mtb) infection, with complex roles in pathogen control and dissemination. Thus, understanding drivers and regulators of granuloma formation is important for improving tuberculosis diagnosis, treatment, and prevention. Yet, molecular mechanisms underpinning granuloma formation and dynamics remain poorly understood.

Myeloid expression is dispensable for skin wound healing and blood vessel regeneration.

Wnt signaling controls blood vessel growth, regression and patterning during embryonic and postnatal life. Macrophages are major producers of Wnt ligands and angiogenic growth factors. It regulates vascular development and specification during embryogenesis and wound healing.

Activity in perirhinal and entorhinal cortex predicts perceived visual similarities among category exemplars with highest precision.

Vision neuroscience has made great strides in understanding the hierarchical organization of object representations along the ventral visual stream (VVS). How VVS representations capture fine-grained visual similarities between objects that observers subjectively perceive has received limited examination so far. In the current study, we addressed this question by focussing on perceived visual similarities among subordinate exemplars of real-world categories.

DLPFC controls the rapid neural response to visual threat: An ERP and rTMS study.

Individuals are faster at detecting threatening stimuli than neutral stimuli. While generally considered a rapid bottom-up response, this threat superiority effect is also modulated by top-down mechanisms known to rely on the dorsolateral prefrontal cortex (DLPFC). What remains unclear is whether the response is modulated only at later stages of processing, or whether rapid attention to threat itself is controlled in a top-down manner.

Neutrophil extracellular traps and their histones promote Th17 cell differentiation directly via TLR2.

Neutrophils perform critical functions in the innate response to infection, including through the production of neutrophil extracellular traps (NETs) - web-like DNA structures which are extruded from neutrophils upon activation. Elevated levels of NETs have been linked to autoimmunity but this association is poorly understood. By contrast, IL-17 producing Th17 cells are a key player in various autoimmune diseases but are also crucial for immunity against fungal and bacterial infections.

Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages.

A hallmark of Listeria (L.) monocytogenes pathogenesis is bacterial escape from maturing entry vacuoles, which is required for rapid bacterial replication in the host cell cytoplasm and cell-to-cell spread. The bacterial transcriptional activator PrfA controls expression of key virulence factors that enable exploitation of this intracellular niche.

The histone deacetylase Hdac7 supports LPS-inducible glycolysis and Il-1β production in murine macrophages via distinct mechanisms.

TLRs reprogram macrophage metabolism, enhancing glycolysis and promoting flux through the tricarboxylic acid cycle to enable histone acetylation and inflammatory gene expression. The histone deacetylase (HDAC) family of lysine deacetylases regulates both TLR-inducible glycolysis and inflammatory responses. Here, we show that the TLR4 agonist LPS, as well as agonists of other TLRs, rapidly increase enzymatic activity of the class IIa HDAC family (HDAC4, 5, 7, 9) in both primary human and murine macrophages.

Rab6b localizes to the Golgi complex in murine macrophages and promotes tumor necrosis factor release in response to mycobacterial infection.

The proinflammatory cytokine tumor necrosis factor (TNF) plays a central role in the host control of mycobacterial infections. Expression and release of TNF are tightly regulated, yet the molecular mechanisms that control the release of TNF by mycobacteria-infected host cells, in particular macrophages, are incompletely understood. Rab GTPases direct the transport of intracellular membrane-enclosed vesicles and are important regulators of macrophage cytokine secretion.

Pre-Diabetes Increases Tuberculosis Disease Severity, While High Body Fat Without Impaired Glucose Tolerance Is Protective.

Type 2 diabetes (T2D) is a well-known risk factor for tuberculosis (TB), but little is known about pre-diabetes and the relative contribution of impaired glucose tolerance obesity towards susceptibility to TB. Here, we developed a preclinical model of pre-diabetes and TB. Mice fed a high fat diet (HFD) for 12 weeks presented with impaired glucose tolerance and hyperinsulinemia compared to mice fed normal chow diet (NCD).

The relationship between adrenocortical candidate gene expression and clinical response to hydrocortisone in patients with septic shock.

Purpose: To determine if adrenocortical gene expression is associated with clinical outcomes or response to corticosteroid treatment in septic shock.

Methods: A pre-specified nested cohort study of a randomised controlled trial of hydrocortisone compared to placebo in septic shock. Blood was collected for RNAseq analysis prior to treatment with hydrocortisone or placebo.