Effectiveness of Cognitive-Behavior Training on Modifying Self and Other- Deception among Females with Irrational Beliefs

Introduction: Self-deception and other-deception can be understood as lying to themselves and others. This research aimed to evaluate the efficacy of cognitive-behavioral intervention on improving self-deception and other-deception in women with irrational beliefs.Methods: This quasi-experimental study was conducted with two groups of experimental and control and by implementation of pre- and post-test, and using sample of 30 participants (15 in experimental group and 15 in control group). The sampling method was convenient method among volunteer women eligible to inclusion-exclusion criteria of research object. Measuring tools were Self-deception and other-deception and irrational beliefs questionnaires. Data were analyzed using MANOVA test.Results: Cognitive-behavioral intervention reduced self-deception, other-deception, and irrational beliefs in the experimental group compared with the control group (P<0.05).Conclusion: According to this results study, cognitive-behavioral therapy can be an efficient intervention for the correction of irrational beliefs, self-deception and other-deception.Declaration of Interest: NoneKey words: Cognitive-behavioral intervention, Irrational beliefs, Self-deception, Other-deception

Modelling Blood Flow and Metabolism in the Piglet Brain During Hypoxia-Ischaemia: Simulating pH Changes

We describe the extension of a computational model of blood flow and metabolism in the piglet brain to investigate changes in neonatal intracellular brain pH during hypoxia-ischemia (HI). The model is able to simulate near-infrared spectroscopy (NIRS) and magnetic resonance spectroscopy (MRS) measurements obtained from HI experiments conducted in piglets. We adopt a method of using (31)P-MRS data to estimate of intracellular pH and compare measured pH and oxygenation with their modelled counterparts. We show that both NIRS and MRS measurements are predicted well in the new version of the model

Immediate remote ischemic postconditioning after hypoxia ischemia in piglets protects cerebral white matter but not grey matter

Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention whereby brief episodes of ischemia/reperfusion of one organ (limb) mitigate damage in another organ (brain) that has experienced severe hypoxia-ischemia. Our aim was to assess whether RIPostC is protective following cerebral hypoxia-ischemia in a piglet model of neonatal encephalopathy (NE) using magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry. After hypoxia-ischemia (HI), 16 Large White female newborn piglets were randomized to: (i) no intervention (n = 8); (ii) RIPostC - with four, 10-min cycles of bilateral lower limb ischemia/reperfusion immediately after HI (n = 8). RIPostC reduced the hypoxic-ischemic-induced increase in white matter proton MRS lactate/N acetyl aspartate (p = 0.005) and increased whole brain phosphorus-31 MRS ATP (p = 0.039) over the 48 h after HI. Cell death was reduced with RIPostC in the periventricular white matter (p = 0.03), internal capsule (p = 0.002) and corpus callosum (p = 0.021); there was reduced microglial activation in corpus callosum (p = 0.001) and more surviving oligodendrocytes in corpus callosum (p = 0.029) and periventricular white matter (p = 0.001). Changes in gene expression were detected in the white matter at 48 h, including KATP channel and endothelin A receptor. Immediate RIPostC is a potentially safe and promising brain protective therapy for babies with NE with protection in white but not grey matter

Preclinical Neonatal Neuroprotection: Neuroprotective effect of Remote Ischemic Postconditioning and dexmedetomidine in a Piglet Model of Perinatal Asphyxia

Perinatal hypoxic ischemic events are a global burden leading to 1.1 million babies with neonatal encephalopathy (NE) annually. Therapeutic hypothermia is a standard practice in developed countries. Still almost 50% of cooled babies have morbidities; Adjunct therapies are needed. This thesis consists of two different preclinical neuroprotection studies. We used a piglet model of perinatal hypoxic ischemia for both studies. Our endpoint biomarkers were immunohistochemistry and in vivo proton (1 H) and phosphorus31 (31P) MRS markers. The first part explores the neuroprotective properties of remote ischemic postconditioning (RIPostC). The second part explores the neuroprotective effect of dexmedetomidine. RIPostC is defined as short cycles of ischemia/reperfusion (I/R) in a remote nonvital organ following a major hypoxic ischemic insult (HI). The first objective was to develop a practical method to achieve intermittent and reversible femoral artery occlusion for remote ischemic stimulus. Second objective was to investigate whether RIPostC immediately applied at resuscitation is neuroprotective following a global cerebral HI in this piglet model. RIPostC cycles were four, 10 minutes cycles of bilateral hind limb I/R immediately after HI. The study showed that RIPostC was neuroprotective in cerebral white matter and also significantly increased whole brain ATP. Immediate RIPostC is a safe procedure. Dexmedetomidine, a highly selective α2-adrenoreceptor agonist exerts analgesic and anti- inflammatory properties. The first objective of this study was to find an optimal safe dose for pre-clinical studies and second objective was to investigate whether substitution of fentanyl with dexmedetomidine for sedation during cooling is neuroprotective. Dexmedetomidine clearance was reduced by 32.7% and 55.8% during cooling and following HI respectively. The PK modelling suggested that a loading dose of 2μg/kg followed by 0.028μg/kg/h provide a safe plasma level. However, the second part of study revealed that dexmedetomidine combined with cooling is neurotoxic and associated with haemodynamic instability

Isoflurane Exposure Induces Cell Death, Microglial Activation and Modifies the Expression of Genes Supporting Neurodevelopment and Cognitive Function in the Male Newborn Piglet Brain

Exposure of the brain to general anesthesia during early infancy may adversely affect its neural and cognitive development. The mechanisms mediating this are complex, incompletely understood and may be sexually dimorphic, but include developmentally inappropriate apoptosis, inflammation and a disruption to cognitively salient gene expression. We investigated the effects of a 6h isoflurane exposure on cell death, microglial activation and gene expression in the male neonatal piglet brain. Piglets (n = 6) were randomised to: (i) naive controls or (ii) 6h isoflurane. Cell death (TUNEL and caspase-3) and microglial activation were recorded in 7 brain regions. Changes in gene expression (microarray and qPCR) were assessed in the cingulate cortex. Electroencephalography (EEG) was recorded throughout. Isoflurane anesthesia induced significant increases in cell death in the cingulate and insular cortices, caudate nucleus, thalamus, putamen, internal capsule, periventricular white matter and hippocampus. Dying cells included both neurons and oligodendrocytes. Significantly, microglial activation was observed in the insula, pyriform, hippocampus, internal capsule, caudate and thalamus. Isoflurane induced significant disruption to the expression of 79 gene transcripts, of these 26 are important for the control of transcription and 23 are important for the mediation of neural plasticity, memory formation and recall. Our observations confirm that isoflurane increases apoptosis and inflammatory responses in the neonatal piglet brain but also suggests novel additional mechanisms by which isoflurane may induce adverse neural and cognitive development by disrupting the expression of genes mediating activity dependent development of neural circuits, the predictive adaptive responses of the brain, memory formation and recall

Modelling Blood Flow and Metabolism in the Piglet Brain During Hypoxia-Ischaemia: Simulating Brain Energetics

We have developed a computational model to simulate hypoxia-ischaemia (HI) in the neonatal piglet brain. It has been extended from a previous model by adding the simulation of carotid artery occlusion and including pH changes in the cytoplasm. Here, simulations from the model are compared with near-infrared spectroscopy (NIRS) and phosphorus magnetic resonance spectroscopy (MRS) measurements from two piglets during HI and short-term recovery. One of these piglets showed incomplete recovery after HI, and this is modelled by considering some of the cells to be dead. This is consistent with the results from MRS and the redox state of cytochrome-c-oxidase as measured by NIRS. However, the simulations do not match the NIRS haemoglobin measurements. The model therefore predicts that further physiological changes must also be taking place if the hypothesis of dead cells is correct. © 2013 Springer Science+Business Media New York

Dexmedetomidine Combined with Therapeutic Hypothermia Is Associated with Cardiovascular Instability and Neurotoxicity in a Piglet Model of Perinatal Asphyxia

The selective α2-adrenoreceptor agonist dexmedetomidine has shown neuroprotective, analgesic, anti-inflammatory, and sympatholytic properties that may be beneficial in neonatal encephalopathy (NE). As therapeutic hypothermia is only partially effective, adjunct therapies are needed to optimize outcomes. The aim was to assess whether hypothermia + dexmedetomidine treatment augments neuroprotection compared to routine treatment (hypothermia + fentanyl sedation) in a piglet model of NE using magnetic resonance spectroscopy (MRS) biomarkers, which predict outcomes in babies with NE, and immunohistochemistry. After hypoxia-ischaemia (HI), 20 large White male piglets were randomized to: (i) hypothermia + fentanyl with cooling to 33.5°C from 2 to 26 h, or (ii) hypothermia + dexmedetomidine (a loading dose of 2 μg/kg at 10 min followed by 0.028 μg/kg/h for 48 h). Whole-brain phosphorus-31 and regional proton MRS biomarkers were assessed at baseline, 24, and 48 h after HI. At 48 h, cell death was evaluated over 7 brain regions by means of transferase-mediated d-UTP nick end labeling (TUNEL). Dexmedetomidine plasma levels were mainly within the target sedative range of 1 μg/L. In the hypothermia + dexmedetomidine group, there were 6 cardiac arrests (3 fatal) versus 2 (non-fatal) in the hypothermia + fentanyl group. The hypothermia + dexmedetomidine group required more saline (p = 0.005) to maintain blood pressure. Thalamic and white-matter lactate/N-acetylaspartate did not differ between groups (p = 0.66 and p = 0.21, respectively); the whole-brain nucleotide triphosphate/exchangeable phosphate pool was similar (p = 0.73) over 48 h. Cell death (TUNEL-positive cells/mm2) was higher in the hypothermia + dexmedetomidine group than in the hypothermia + fentanyl group (mean 5.1 vs. 2.3, difference 2.8 [95% CI 0.6-4.9], p = 0.036). Hypothermia + dexmedetomidine treatment was associated with adverse cardiovascular events, even within the recommended clinical sedative plasma level; these may have been exacerbated by an interaction with either isoflurane or low body temperature. Hypothermia + dexmedetomidine treatment was neurotoxic following HI in our piglet NE model, suggesting that caution is vital if dexmedetomidine is combined with cooling following NE

Surgery increases cell death and induces changes in gene expression compared with anesthesia alone in the developing piglet brain

<div><p>In a range of animal species, exposure of the brain to general anaesthesia without surgery during early infancy may adversely affect its neural and cognitive development. The mechanisms mediating this are complex but include an increase in brain cell death. In humans, attempts to link adverse cognitive development to infantile anaesthesia exposure have yielded ambiguous results. One caveat that may influence the interpretation of human studies is that infants are not exposed to general anaesthesia without surgery, raising the possibility that surgery itself, may contribute to adverse cognitive development. Using piglets, we investigated whether a minor surgical procedure increases cell death and disrupts neuro-developmental and cognitively salient gene transcription in the neonatal brain. We randomly assigned neonatal male piglets to a group who received 6h of 2% isoflurane anaesthesia or a group who received an identical anaesthesia plus 15 mins of surgery designed to replicate an inguinal hernia repair. Compared to anesthesia alone, surgery-induced significant increases in cell death in eight areas of the brain. Using RNAseq data derived from all 12 piglets per group we also identified significant changes in the expression of 181 gene transcripts induced by surgery in the cingulate cortex, pathway analysis of these changes suggests that surgery influences the thrombin, aldosterone, axonal guidance, B cell, ERK-5, eNOS and GABA_A signalling pathways. This suggests a number of novel mechanisms by which surgery may influence neural and cognitive development independently or synergistically with the effects of anaesthesia.</p></div