Physiological skin oxygen levels: An important criterion for skin cell functionality and therapeutic approaches.

The skin is made up of different layers with various gradients, which maintain a complex microenvironment, particularly in terms of oxygen levels. However, all types of skin cells are cultured in conventional incubators that do not reproduce physiological oxygen levels. Instead, they are cultured at atmospheric oxygen levels, a condition that is far removed from physiology and may lead to the generation of free radicals known to induce skin ageing.

Threat of shock increases distractor susceptibility during the short-term maintenance of visual information.

Elevated arousal in anxiety is thought to affect attention control. To test this, we designed a visual short-term memory (VSTM) task to examine distractor suppression during periods of threat and no-threat. We hypothesized that threat would impair performance when subjects had to filter out large numbers of distractors.

Threat of shock increases distractor susceptibility during the short-term maintenance of visual information.

Background: Work on anxiety related attention control deficits suggests that elevated arousal impacts the ability to filter out distractors. To test this, we designed a task to look at distractor suppression during periods of threat. We administered trials of a visual short-term memory (VSTM) task, during periods of unpredictable threat, and hypothesized that threat would impair performance during trials where subjects were required to filter out large numbers of distractors.

A neural oscillatory signature of sustained anxiety.

Background: Anxiety is a sustained response to uncertain threats; yet few studies have explored sustained neurobiological activities underlying anxious states, particularly spontaneous neural oscillations. To address this gap, we reanalysed magnetoencephalographic (MEG) data recorded during induced anxiety to identify differences in sustained oscillatory activity between high- and low-anxiety states.

Methods: We combined data from three previous MEG studies in which healthy adults (total N = 51) were exposed to alternating periods of threat of unpredictable shock and safety while performing a range of cognitive tasks (passive oddball, mixed-saccade or stop-signal tasks).

Improvement of Antioxidant Defences in Keratinocytes Grown in Physioxia: Comparison of 2D and 3D Models.

Keratinocytes prevent skin photoaging by ensuring the defence against oxidative stress, an excessive production of reactive oxygen species (ROS). They are localized within the epidermis where the oxygen level (1-3% O), named physioxia, is low compared to other organs. Oxygen is essential for life but also generates ROS.

Attenuation of Anxiety-Potentiated Startle After Treatment With Escitalopram or Mindfulness Meditation in Anxiety Disorders.

Background: Biological markers for anxiety disorders may further understanding of disorder pathophysiology and suggest potential targeted treatments. The fear-potentiated startle (FPS) (a measure of startle to predictable threat) and anxiety-potentiated startle (APS) (startle to unpredictable threat) laboratory paradigm has been used to detect physiological differences in individuals with anxiety disorders compared with nonanxious control individuals, and in pharmacological challenge studies in healthy adults. However, little is known about how startle may change with treatment for anxiety disorders, and no data are available regarding alterations due to mindfulness meditation training.

Periaqueductal gray matter and medial prefrontal cortex reflect negative prediction errors during differential conditioning.

Computational models of associative learning posit that negative prediction errors (PEs) arising from the omission of aversive outcomes weaken aversive Pavlovian associations during differential conditioning and extinction. It is possible that negative PEs may underlie exaggerated conditioned responses to the conditioned stimulus not paired with an aversitve outcome (CS-) during differential conditioning and to the conditioned stimulus originally paired with a aversive outcome (CS+) during extinction in patients with clinical anxiety disorders. Although previous research has demonstrated that manipulations of the periaqueductal gray matter (PAG) interfere with extinction learning in animals, the role of the PAG in processing negative PEs within the human brain is presently unclear.

Enduring impact of childhood adversity: Affective modulation of acoustic startle response during pregnancy and postpartum.

Background: Women with a history of adverse childhood experiences (ACEs) enter pregnancy and the postpartum with a physiologic system programmed by early life stress, potentially reflected in psychophysiologic reactivity.

Methods: We enrolled pregnant, psychiatrically healthy women ≥18 years old. Using the ACE Questionnaire, women were categorized as high (≥2 ACEs; n = 77) or low ACE (<2 ACEs; n = 72).

Longitudinal Trajectory of the Link Between Ventral Striatum and Depression in Adolescence.

Objective: Research in adolescent depression has found aberrant intrinsic functional connectivity (iFC) among the ventral striatum (VS) and several brain regions implicated in reward processing. The present study probes this question by taking advantage of the availability of data from a large youth cohort, the IMAGEN Consortium.

Methods: iFC data from 303 adolescents (48% of them female) were used to examine associations of VS connectivity at baseline (at age 14) with depressive disorders at baseline and at 2-year (N=250) and 4-year (N=219) follow-ups.

The Posterior Cingulate Cortex Reflects the Impact of Anxiety on Drift Rates During Cognitive Processing.

Background: Generally, anxiety is thought to impair ongoing cognitive operations. Surprisingly, however, anxiety has been shown to improve performance during the Go/NoGo task. Understanding how anxiety can facilitate task performance may shed light on avenues to address the cognitive deficits commonly associated with anxiety.

Location-dependent threat and associated neural abnormalities in clinical anxiety.

Anxiety disorders are characterized by maladaptive defensive responses to distal or uncertain threats. Elucidating neural mechanisms of anxiety is essential to understand the development and maintenance of anxiety disorders. In fMRI, patients with pathological anxiety (ANX, n = 23) and healthy controls (HC, n = 28) completed a contextual threat learning paradigm in which they picked flowers in a virtual environment comprising a danger zone in which flowers were paired with shock and a safe zone (no shock).

Methylphenidate modulates interactions of anxiety with cognition.

While a large body of literature documents the impairing effect of anxiety on cognition, performing a demanding task was shown to be effective in reducing anxiety. Here we explored the mechanisms of this anxiolytic effect by examining how a pharmacological challenge designed to improve attentional processes influences the interplay between the neural networks engaged during anxiety and cognition. Using a double-blind between-subject design, we pharmacologically manipulated working memory (WM) using a single oral dose of 20 mg methylphenidate (MPH, cognitive enhancer) or placebo.

Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group.

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis.

Dynamic Time Warping Identifies Functionally Distinct fMRI Resting State Cortical Networks Specific to VTA and SNc: A Proof of Concept.

Functional connectivity (FC) is determined by similarity between functional magnetic resonance imaging (fMRI) signals from distinct brain regions. However, traditional FC analyses ignore temporal phase differences. Here, we addressed this limitation, using dynamic time warping (DTW) within a machine-learning framework, to study cortical FC patterns of 2 spatially adjacent but functionally distinct subcortical regions, namely Substantia Nigra Pars Compacta (SNc) and ventral tegmental area (VTA).

Response to sertraline is associated with reduction in anxiety-potentiated startle in premenstrual dysphoric disorder.

Rationale: Women with premenstrual dysphoric disorder (PMDD) appear to have altered central nervous system sensitivity to neuroactive steroid hormones, manifesting as affective symptoms and heightened arousal in the luteal phase of the menstrual cycle. In particular, women with PMDD appear less sensitive to allopregnanolone, a positive allosteric GABA-A receptor (GABA-A-R) modulator.

Objectives: This study evaluated psychophysiologic reactivity in women with PMDD in the follicular and luteal phases of the menstrual cycle, utilizing anxiety-potentiated startle (APS), a potential translational marker of GABA-A-R sensitivity.

Neurophysiological and clinical effects of the NMDA receptor antagonist lanicemine (BHV-5500) in PTSD: A randomized, double-blind, placebo-controlled trial.

Background: Posttraumatic stress disorder (PTSD) is associated with hyperarousal and stress reactivity, features consistent with behavioral sensitization. In this Phase 1b, parallel-arm, randomized, double-blind, placebo-controlled trial, we tested whether the selective low-trapping N-methyl-D-aspartate receptor (NMDAR) antagonist [Lanicemine (BHV-5500)] blocks expression of behavioral sensitization.

Methods: Twenty-four participants with elevated anxiety potentiated startle (APS) and moderate-to-severe PTSD symptoms received three infusions of lanicemine 1.

The novel vasopressin receptor (V1aR) antagonist SRX246 reduces anxiety in an experimental model in humans: a randomized proof-of-concept study.

Rationale: Arginine vasopressin (AVP) is a neuropeptide that modulates both physiological and emotional responses to threat. Until recently, drugs that target vasopressin receptors (V1a) in the human central nervous system were unavailable. The development of a novel V1a receptor antagonist, SRX246, permits the experimental validation of vasopressin's role in the regulation of anxiety and fear in humans.

Prefrontal Responses during Proactive and Reactive Inhibition Are Differentially Impacted by Stress in Anorexia and Bulimia Nervosa.

Binge eating is a distressing, transdiagnostic eating disorder symptom associated with impulsivity, particularly in negative mood states. Neuroimaging studies of bulimia nervosa (BN) report reduced activity in frontostriatal regions implicated in self-regulatory control, and an influential theory posits that binge eating results from self-regulation failures under stress. However, there is no direct evidence that psychological stress impairs self-regulation in binge-eating disorders, or that any such self-regulatory deficits generalize to binge eating in underweight individuals (i.

Tumour angiogenesis normalized by myo-inositol trispyrophosphate alleviates hypoxia in the microenvironment and promotes antitumor immune response.

Pathologic angiogenesis directly responds to tumour hypoxia and controls the molecular/cellular composition of the tumour microenvironment, increasing both immune tolerance and stromal cooperation with tumour growth. Myo-inositol-trispyrophosphate (ITPP) provides a means to achieve stable normalization of angiogenesis. ITPP increases intratumour oxygen tension (pO ) and stabilizes vessel normalization through activation of endothelial Phosphatase-and-Tensin-homologue (PTEN).

Deleterious Effects of an Air Pollutant (NO) on a Selection of Commensal Skin Bacterial Strains, Potential Contributor to Dysbiosis?

The skin constitutes with its microbiota the first line of body defense against exogenous stress including air pollution. Especially in urban or sub-urban areas, it is continuously exposed to many environmental pollutants including gaseous nitrogen dioxide (gNO). Nowadays, it is well established that air pollution has major effects on the human skin, inducing various diseases often associated with microbial dysbiosis.

Soluble Guanylate Cyclase Inhibitors Discovered among Natural Compounds.

Soluble guanylate cyclase (sGC) is the human receptor of nitric oxide (NO) in numerous kinds of cells and produces the second messenger 3',5'-cyclic guanosine monophosphate (cGMP) upon NO binding to its heme. sGC is involved in many cell signaling pathways both under healthy conditions and under pathological conditions, such as angiogenesis associated with tumor growth. Addressing the selective inhibition of the NO/cGMP pathway is a strategy worthwhile to be investigated for slowing down tumoral angiogenesis or for curing vasoplegia.

The GTPase-activating protein-related domain of neurofibromin interacts with MC1R and regulates pigmentation-mediated signaling in human melanocytes.

The melanocortin 1 receptor (MC1R) is a G-protein coupled receptor (GPCR) which plays a major role in controlling melanogenesis. A large body of evidence indicates that GPCRs are part of large protein complexes that are critical for their signal transduction properties. Among proteins which may affect MC1R signaling, neurofibromin (Nf1), a GTPase activating protein (GAP) for Ras, is of special interest as it regulates adenylyl cyclase activity and ERK signaling, two pathways involved in MC1R signaling.

Responding to uncertain threat: A potential mediator for the effect of mindfulness on anxiety.

Mindfulness-based interventions have gained extensive support for their application in the treatment of anxiety. However, their mechanisms remain largely unexplored. Excessive reactivity to uncertainty plays a central role in anxiety, and may represent a mechanism for the effect of mindfulness on anxiety, as mindfulness training fosters an open and accepting stance towards all aspects of experience.

Patients with anxiety disorders rely on bilateral dlPFC activation during verbal working memory.

One of the hallmarks of anxiety disorders is impaired cognitive control, affecting working memory (WM). The dorsolateral prefrontal cortex (dlPFC) is critical for WM; however, it is still unclear how dlPFC activity relates to WM impairments in patients. Forty-one healthy volunteers and 32 anxiety (general and/or social anxiety disorder) patients completed the Sternberg WM paradigm during safety and unpredictable shock threat.