Effects of hyperbaric oxygen therapy on autistic behaviors and GRIN2B gene expression in valproic acid-exposed rats.

Introduction: Autism is a complex neurodevelopmental condition characterized by deficits in social interaction, communication, and restricted repetitive behaviors. Hyperbaric oxygen therapy (HBOT) has emerged as a potential treatment for autism, although its effects on behavior and gene expression are not well understood. The GRIN2B gene, known for its involvement in encoding a glutamate receptor subunit crucial for neuron communication and associated with autism, was a focus of this study. Methods: Using a rat model induced by prenatal exposure to valproic acid, we examined the impact of HBOT on autism-like behaviors and GRIN2B gene expression. Male Wistar rats were categorized into four groups: control, VPA (valproic acid-exposed), VPA+HBOT [2 atmosphere absolute (ATA)], and VPA+HBOT (2.5 ATA). The rats underwent several behavioral tests to assess social behavior, anxiety, stereotype and exploratory behaviors, and learning. Following the behavioral tests, the HBOT groups received 15 sessions of HBOT at pressures of 2 and 2.5 (ATA), and their behaviors were re-evaluated. Subsequently, real-time PCR was employed to measure GRIN2B gene expression in the frontal lobe. Results: Our results indicated that HBOT significantly increased social interaction and exploratory behaviors in VPA-exposed rats, alongside elevated GRIN2B gene expression in their frontal lobe. Discussion: Our findings imply that HBOT might have a potential role in ameliorating autism-related behaviors in the VPA rat model of autism through potential modulation of GRIN2B gene expression. However, additional research is essential to fully comprehend the underlying mechanisms and refine the HBOT protocol for optimizing its effectiveness in improving autism-related symptoms.

A novel removal of Ni2+ ions from water solutions using dispersive solid-phase extraction method with nano Fe3O4/chitosan-acrylamide hydrogel.

The effluent release containing heavy metals as Ni2+ ions has drastic risks to both the natural environment and human health. In this research, the nano Fe3O4/chitosan-acrylamide hydrogel was prepared as a novel nano sorbent for dispersive solid-phase extraction of Ni2+ ions and applied to the water sample solution. The pH, amount and type of elution solvent, the extraction time, etc. were optimized to improve the efficiency of the proposed method. Analytical parameters such as concentration factor and relative standard deviation (%) were achieved as 33.3 and 1.8%, respectively. The capacity in equilibrium sorption was calculated at 22.54 mg g-1. Furthermore, to estimate the adsorption mode, Freundlich, Langmuir, and Temkin models were fitted with experimental isotherm data. Besides, to check the basic process of the metal adsorption mechanism, pseudo-first-order, pseudo-second-order, and Roginsky-Zeldovich models were investigated and the results were fitted with the pseudo-second-order model. The value of change in entropy (⊿S) obtained is -65.24 (J(mol K)-1). Negative values of change in enthalpy, ⊿H in (kJ mol-1) is -24.45 (kJ mol-1) which indicates both physical and chemical adsorptions involved in the process of adsorption. Finally, the nano Fe3O4/chitosan-acrylamide hydrogel exhibited high performance to remove the Ni2+ ions from water sample solution.

Disgust-reduction evaluative conditioning (DREC) and brain stimulation in patients with contamination-based obsessive-compulsive disorder: a protocol for a randomized control trial.

BACKGROUND: The negative emotional valence of a stimulus can be altered if paired with a pleasant stimulus, a phenomenon referred to as evaluative conditioning. Disgust, as a central emotion in obsessive-compulsive disorder (OCD), particularly in the contamination subtype, may be an appropriate target for such a method. We know that disgust processing and OCD pathophysiology share in some brain areas, including the orbitofrontal cortex, as the neuromodulation techniques targeted in this area have been able to decrease OCD symptoms. We aim to conduct a randomized clinical trial to investigate the evaluative conditioning effect on disgust reduction in patients with contamination-based OCD when administered with or without neuromodulation targeted orbitofrontal cortex. METHOD: In a single-blind randomized control trial (RCT), 55 patients with contamination-based OCD will be randomly assigned to four arms. In a factorial design, they will receive 10 sessions of evaluative conditioning training (either sham or real) plus cathodal transcranial direct current stimulation (tDCS) over the orbitofrontal cortex (either sham or real). The intensity of disgust experience and clinical symptoms will be investigated as primary outcomes and quantitative electroencephalogram and cognitive functions as secondary outcomes. The data will be collected at three assessment levels: baseline, after completing intervention sessions, and 2-month follow-up. DISCUSSION: The present RCT is the first study that applies evaluative conditioning training in the OCD clinical sample. It will clarify the effect of the evaluative conditioning method alone and with tDCS on disgust reduction in patients with contamination-based OCD. It will provide initial evidence for such an emotion modulation method in the OCD population. The effect of this emotion-focused protocol on cognitive functions and electroencephalogram components is also of interest. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05907369. Registered on 16 June 2023. Retrospectively registered.

Behavioral and electrophysiological (ECoG) effects of haplophyllum robustum and TRPA1 antagonist in adult male wistar rats.

This article aimed to investigate the effects of Haplophyllum robustum hydroalcoholic extract on animals' behavioral and electrocorticographic changes. This plant is mainly found in Turkey, Iran, and Central Asia, and is reported to have convulsive effects. In this article, we worked on the effects of its hydroalcoholic extract on electrocorticography (ECoG), along with changes induced by intracerebroventricular administration of GABAA antagonists. Furthermore, the effects of low doses of this extract on behavioral depression were examined. Four animal sets were used to compare ECoG in Wistar rats. A group of negative control, a group of positive control (PTZ), and two groups received an injection of plant extract (500 mg/kg, ip), with or without administration of Diazepam (5 mg/kg). Also, three sets were applied to compare receiving and not receiving intracerebroventricular (icv) injection of Transient receptor potential ankyrin 1 antagonist (HC-030031) (2 µg/kg) on plant-induced seizure delay and animal death. Two groups of control and a group with plant extract together with TRPA1 antagonist were administrated. Furthermore, in the present study, the forced swimming test (FST) was used as a model of depression. The behaviors of animals in three groups of negative control and positive control (Fluoxetine) and plant extract (200 mg/kg, ip) were compared. According to the ECoG, high doses of extract of plants led to seizures similar to PTZ, which were then reduced by diazepam injection. At this dose, injection of TRPA1 antagonist did not significantly delay the onset of seizures or the death of the animals. Further, a subconvulsive dose of hydroalcoholic plant extracts was equally effective in treating depression as Fluoxetine injections.

Effect of stress on spatial working memory and EEG signal dynamics in the follicular and luteal phases of the menstrual cycle in young single girls.

AIM: Women undergo behavioral changes during the menstrual cycle. This study aimed to investigate the effect of estradiol (Es) on stress and effect of stress on spatial working memory (WM) and also to investigate electroencephalogram (EEG) signal's dynamics in the early and late follicular (EF and LF) and luteal (LU) phases of unmarried girls' menstrual cycle. METHODS: Stress was induced by presentation of a short (3 min) movie clip. Simultaneous with a memory test and stress induction, EEG, serum Es levels, and galvanic skin response (GSR) were assessed. RESULTS: Serum Es concentrations were decreased in LF, LU, and EF phases. The mean GSR score decreased after stress induction in all three phases, but it increased in the LF and LU phases versus the EF phase. Spatial WM diminished after stress induction in all three phases, but it increased in the LF phase versus the two phases before and after stress induction. Average power spectrum density in all frequency bands increased after stress induction in the frontal and prefrontal channels in the spatial WM test. CONCLUSION: The results showed that stress led to spatial WM dysfunction; however, Es improved spatial WM performance in the LF phase versus the other two phases.

Validation of a tool for determining the clinical utility of stillbirth investigations.

BACKGROUND: Up to 20% of all stillbirths and 45% of term stillbirths are currently classified as unexplained. Many of these stillbirths do not undergo currently recommended investigations. This may leave questions unanswered and not identify stillbirths with a recurrence risk in subsequent pregnancies. AIMS: To validate a new tool (Stillbirth Investigation Utility Tool) to identify the clinical utility of investigations in stillbirth and the inter-rater agreement on cause of stillbirth using the Perinatal Society of Australia and New Zealand-Perinatal Death Classification (PSANZ-PDC). MATERIALS AND METHODS: Thirty-four stillbirths were randomly selected for inclusion, each assessed independently by five blinded assessors. The investigations were grouped into three categories: clinical and laboratory; placental pathology; and autopsy examination. The cause of death was assigned at the end of each group. Outcome measures were clinical utility of investigations measured by assessor rated usefulness and inter-rater agreement on the assigned cause of death. RESULTS: Comprehensive maternal history, maternal full blood count, maternal blood group and screen and placenta histopathology were useful in all cases. Clinical photographs were not performed and should have been performed in 50% of cases. The inter-rater agreement on cause of death assigned after all investigation results was 0.93 (95% CI 0.87-1.0). CONCLUSIONS: The new Stillbirth Investigation Utility Tool showed very good agreement in assigning the cause of death using PSANZ-PDC. Four investigations were useful in all cases. Minor refinements will be made based on feedback to enhance usability for wider implementation in research studies to assess the yield of investigations in stillbirths.

Extraction of alprazolam in biological samples using the dispersive solid-phase method with nanographene oxide grafted with α-pyridylamine.

An effective adsorbent was synthesised from nanographene oxide for the removal of the alprazolam drug from the water sample solution. The dispersive solid-phase extraction method was used with α-pyridylamine grafted nanographene oxide to extract and analyse little amounts of alprazolam in biological materials. Before beginning the experimental analysis process, it is critical to use a simple and accessible sample preparation approach. In the current study, a technique for preconcentration and measurement of trace quantities of alprazolam in aqueous samples was introduced. The pH of extraction, the amount and type of elution solvent and the period of extraction were all tuned in the alprazolam analysis technique. Analytical parameters such as the concentration factor, the limit of detection of the technique and relative standard deviation (%) were achieved as 20, 8.0 µg L-1 and 2.4%, respectively.

Diet-induced maternal obesity impacts feto-placental growth and induces sex-specific alterations in placental morphology, mitochondrial bioenergetics, dynamics, lipid metabolism and oxidative stress in mice.

AIM: The current study investigated the impact of maternal obesity on placental phenotype in relation to fetal growth and sex. METHODS: Female C57BL6/J mice were fed either a diet high in fat and sugar or a standard chow diet, for 6 weeks prior to, and during, pregnancy. At day 19 of gestation, placental morphology and mitochondrial respiration and dynamics were assessed using high-resolution respirometry, stereology, and molecular analyses. RESULTS: Diet-induced maternal obesity increased the rate of small for gestational age fetuses in both sexes, and increased blood glucose concentrations in offspring. Placental weight, surface area, and maternal blood spaces were decreased in both sexes, with reductions in placental trophoblast volume, oxygen diffusing capacity, and an increased barrier to transfer in males only. Despite these morphological changes, placental mitochondrial respiration was unaffected by maternal obesity, although the influence of fetal sex on placental respiratory capacity varied between dietary groups. Moreover, in males, but not females, maternal obesity increased mitochondrial complexes (II and ATP synthase) and fission protein DRP1 abundance. It also reduced phosphorylated AMPK and capacity for lipid synthesis, while increasing indices of oxidative stress, specifically in males. In females only, placental mitochondrial biogenesis and capacity for lipid synthesis, were both enhanced. The abundance of uncoupling protein-2 was decreased by maternal obesity in both fetal sexes. CONCLUSION: Maternal obesity exerts sex-dependent changes in placental phenotype in association with alterations in fetal growth and substrate supply. These findings may inform the design of personalized lifestyle interventions or therapies for obese pregnant women.

Protective effect of Toll-like receptor 4 antagonist on inflammation, EEG, and memory changes following febrile seizure in Wistar rats.

Neuroinflammation and fever are the main triggers in febrile seizures (FS). Focusing on inflammatory pathways and anti-inflammatory drugs could compensate for the limitations of existing medications. The aim of this study is to evaluate the neuroprotective effect of specific antagonizing Toll-like receptor 4 (TLR4), as a prominent inflammatory axis, on the consequences of FS and adulthood using animal models. Complex FS was induced on 9-11 day old male rat pups using a heated chamber. TAK-242, as a specific TLR4 inhibitor, was injected intraperitoneally before seizure induction. Seizure threshold, duration, and spike number were measured by electrocorticography. The levels of inflammatory cytokines, TLR4 protein expression, and oxidative stress markers were detected by enzyme-linked immunosorbent assay, western blotting, malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) assessments in the cortex and hippocampus. Also, spatial and non-spatial memory were evaluated using the novel object recognition test (NORT) and double Y-maze test during adulthood. The results revealed that provoked inflammatory responses in neonate rats, after FS, were associated with the increase of the tumor necrosis factor alpha, interleukin-1ß, and enhanced TLR4 protein expression. Meanwhile, based on performed behavioral tests, the inflammatory process was also involved in adulthood memory deficit. Pretreatment with TAK-242 reduced the inflammatory cytokines and TLR4 protein expression in the cortex and hippocampus of neonate rats and improvement in memory deficit in NORT and double Y-maze tasks. Also, pretreatment with TAK-242 elevated seizure threshold, SOD, and CAT activities, and decreased seizure duration and MDA level with no significant change in spike number. TAK-242 possibly controlled FS via inhibiting inflammation.

Fabrication of superparamagnetic adsorbent based on layered double hydroxide as effective nanoadsorbent for removal of Sb (III) from water samples.

In this study, the superparamagnetic adsorbent as Fe@Mg-Al LDH was synthesised by different methods with two steps for the removal of heavy metal ions from water samples. An easy, practical, economical, and replicable method was introduced to remove water contaminants, including heavy ions from aquatic environments. Moreover, the structure of superparamagnetic adsorbent was investigated by various methods including Fourier transform infrared spectroscopy, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, and vibrating sample magnetometer. For better separation, ethylenediaminetetraacetic acid ligand was used, forming a complex with antimony ions to create suitable conditions for the removal of these ions. Cadmium and antimony ions were studied by floatation in aqueous environments with this superparamagnetic adsorbent owing to effective factors such as pH, amount of superparamagnetic adsorbent, contact time, sample temperature, volume, and ligand concentration. The model of Freundlich, Langmuir, and Temkin isotherms was studied to qualitatively evaluate the adsorption of antimony ions by the superparamagnetic adsorbent. The value of loaded antimony metal ions with Fe@Mg-Al LDH was resulted at 160.15 mg/g. The standard deviation value in this procedure was found at 7.92%. The desorption volume of antimony metal ions by the adsorbent was found to be 25 ml. The thermodynamic parameters as well as the effect of interfering ions were investigated by graphite furnace atomic absorption spectrometry.

Acinar Melanosis of the Bartholin Gland: A Report of 3 Cases.

Melanocytic pigmentation occurs in multiple sites in the lower female genital tract, but is rare within benign cysts of the vulva. We report 3 patients with multiloculated cystic lesions of the vulvar vestibule exhibiting prominent melanocytic pigmentation. The current cases differ from a previous report of melanosis in a Bartholin gland cyst in that the population of melanocytes occupies the acinar structures of the gland, rather than a squamous-lined surface. A similar cell population is demonstrated by immunoperoxidase methods in a fourth patient's nonpigmented gland, suggesting that melanin production may arise in a native, rather than metaplastic, cell population.

Magnetic nanobiosorbent (MG-Chi/Fe3 O4 ) for dispersive solid-phase extraction of Cu(II), Pb(II), and Cd(II) followed by flame atomic absorption spectrometry determination.

Trace amounts of Cu (II), Pb (II), and Cd (II) in a wastewater sample were preconcentrated with a novel cross-linked magnetic chitosan modified with a new synthesised methionine-glutaraldehyde Schiff's base (MG-Chi/Fe3 O4 ) as a dispersive solid-phase extraction (DSPE) adsorbent. The adsorbed metal ions were then eluted with a specific volume of suitable solution and determined by flame atomic absorption spectrometry (FAAS). Various parameters affecting the extraction efficiency of the metal ions were investigated and optimised, including pH, amount of adsorbent, extraction time, type and volume rate of eluent, elution time, sample volume, and effect of interfering ions. The adsorption kinetics are more consistent with the pseudo-second order model. The results were statistically interpreted and the analytical performance of the proposed method was found to have preconcentration factors of 55, 60, and 50 µg L-1 for Cu(II), Pb(II), and Cd(II), respectively, limits of detection were 0.22, 0.24, and 0.10 µg L-1 for Cu(II), Pb(II), and Cd(II), respectively, with a relative standard deviation (1.5%-2.8 %), and the liner range was 5-1000 for Cu(II) and Pb(II) and 2.5-1000 for Cd(II). It was concluded that this method was suitable for successful simultaneous determination of Cu(II), Pb(II), and Cd(II) in industrial wastewater samples.

A rapid and sensitive method for separation of Cu2+ ions from industrial wastewater sample and water samples with methacrylamide-ethylene glycol dimethacrylate: A new synthesis of molecularly imprinted polymer.

In this study, new molecularly imprinted polymer particles (MIP) were synthesised to extract Cu2+ ions from aqueous solutions using radical polymerisation. MIP was developed using the methacrylamide-ethylene glycol dimethacrylate (EGDMA) cross linking agent, methacrylamide monomer, and ACV initiator by the radical polymerisation method. A comparison of various cross linking agents in MIP production showed that the best cross linking agents are EGDMA and gallic acid. The template ions were removed by leaching with 0.100 M HCl. The polymer particles were characterised by FTIR spectroscopy, thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The effect of different parameters such as cross linkers, pH, time, maximum adsorption capacity, and kinetic and isotherm adsorption were investigated. The best conditions were determined (pH = 8.0, t = 10 min, and qm  = 262.53 mg g-1 ). The adsorption data were best fitted by Freundlich isotherm and pseudo second order kinetic models, as well. Due to its high adsorption capacity and multi-layer behaviour, this method is an easy, fast and safe way to extract cations. Removal of Cu2+ in certified tap water and rain water was demonstrated and the industrial wastewater sample (Charmshahr, Iran) with which the MIP was developed using Methacrylamide- Ethylene Glycol Dimethacrylate (EGDMA) was good enough for Cu2+ determination in matrices containing components with similar chemical property such as Co2+ , Zn2+ , Fe2 .

Bursting-bubble flow microextraction combined with gas chromatography to analyze organophosphorus pesticides in aqueous samples.

Bubble-bursting flow microextraction combined with gas chromatography as a green and sustainable microextraction method is used to determine some organophosphorus pesticide residues in water samples. The extraction process occurs at the surface of liquid-gas contact, where the analytes interact with the gas molecules in the bubble. The analytes are transferred to the surface of the sample solution by moving the gas bubbles upwards. The bursting of gas bubbles causes the analytes to disperse in the headspace. Eventually, they are collected for injection into the chromatography system. A one-factor-at-one-time approach was applied to optimize the independent variables in the proposed method. Validation studies were performed according to reliable guidelines. Under optimal conditions, the method indicated a dynamic linear range from 1.0 to 100.0 µg/L. The limit of detection and quantification of the method was 0.29-0.38 and 1.21-1.70 µg/L, respectively. The proposed method was successfully utilized to determine malathion, diazinon, profenofos, and ethion as the target analytes in various water samples with satisfactory relative recoveries ranged from 90.1 to 102.2%.

Bilateral congenital pulmonary airway malformation in an extremely preterm infant.

We present the case of a baby boy, with antenatal finding of bilateral enlarged echogenic lungs, who developed severe postnatal respiratory failure. Two important differential diagnoses, which have an impact on antenatal and postnatal management, are discussed. Fetal ultrasound, MRI and postmortem MRI images are presented and findings correlated with the autopsy findings.

Pharmacological upregulation of GLT-1 alleviates the cognitive impairments in the animal model of temporal lobe epilepsy.

It is known that hippocampal epileptogenesis is accompanied by hyperexcitability, glutamate-related neuronal dysfunctions and consequently cognitive deficits. However, the neuroprotective role of astrocytic glutamate uptake through the Glutamate Transporter-1 (GLT-1) remains to be unknown in these processes. Therefore, to assess the effect of glutamate uptake, pharmacological upregulation of GLT-1 using ceftriaxone administration (200 mg/kg/day, i.p, 5 days) was utilized in Li-PIL animal models of temporal lobe epilepsy (TLE). Glutamate concentration and glutamine synthetase activity were analyzed using biochemical assays. In addition, GLT-1 gene expression was assessed by RT-qPCR. Finally, cognitive function was studied using Morris water maze (MWM) test and novel object recognition task (NORT). Our results demonstrated that the acute phase of epileptogenesis (first 72 hours after Status Epilepticus) was accompanied by an increase in the hippocampal glutamate and downregulation of GLT-1 mRNA expression compared to controls. Ceftriaxone administration in epileptic animals led to a reduction of glutamate along with elevation of the level of glutamine synthetase activity and GLT-1 expression in the acute phase. In the chronic phase of epileptogenesis (4 weeks after Status Epilepticus), glutamate levels and GLT-1 expression were decreased compared to controls. Ceftriaxone treatment increased the levels of GLT-1 expression. Furthermore, impaired learning and memory ability in the chronic phase of epileptogenesis was rescued by Ceftriaxone administration. This study shows that astrocytic glutamate uptake can profoundly impact the processes of hippocampal epileptogenesis through the reduction of glutamate-induced excitotoxicity and consequently rescuing of cognitive deficits caused by epilepsy.

The differentiation effect of bone morphogenetic protein (BMP) on human amniotic epithelial stem cells to express ectodermal lineage markers.

Stem cells are a promising tool for treatment of a variety of degenerative diseases. Human amniotic epithelial stem cells (hAECs) have desirable and unique characteristics that make them a proper candidate for cell therapy. In this study, we have investigated the effects of BMP-4 (bone morphogenetic protein-4) and its inhibition on differentiation of AECs into ectodermal lineages. Analysis of AEC-derived ectodermal lineages (neurons and keratinocytes) was performed by using flow cytometry technique for Map2 and ß-tubulin (as neuron markers), Olig2 and MBP (as oligodendrocyte markers), and K14 and K10 (as keratinocyte markers). The results of this study illustrated that noggin (as BMP antagonist), BMP4, and both BMP4 and heparin (together or separately) increased neural and keratinocyte marker expression, respectively. The expression of markers MAP2, olig2, and K14 in hAECs has been significantly decreased 21 days after exposure to differentiation medium (without growth factors) compared with isolation day, which supports the hypothesis that AECs can be dedifferentiated into pluripotent cells. Moreover, activation and inhibition of BMP signaling have no effects on viability of hAECs. The results of this study showed that BMP signaling and its inhibition are the key factors for ectodermal lineage differentiation of amnion-derived stem cells.

The Investigation of Simultaneous EEG and Eye Tracking Characteristics During Fixation Task in Mild Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that occurs many years before the first clinical symptoms. Finding more exact, significant, and valuable criteria or indices for the diagnosis of the mild form of Alzheimer's disease is very important for clinical and research purposes. Electroencephalography (EEG) and eye tracking biomarkers would provide noninvasive tools for the early detection of AD. Due to the advantages of EEG and eye tracking, in this study, we employed them simultaneously to conduct research on the mild AD. For this purpose, 19 patients with mild AD were compared with 19 gender- and age-matched normal subjects who did not have any history of cognitive or neurological disorders. EEG and eye-tracking data were concurrently collected in both groups in a fixation task. Our results revealed that the total fixation duration was significantly shorter for the AD patients, but their fixation frequency was more than that of the controls. In addition, increased theta power and decreased alpha power were observed in the AD group. Interestingly, there was a statistically significant correlation between fixation frequency and alpha power in the parietal area in the control group. However, this connection was not statistically significant in the AD group. The findings also indicated an elevated coherence in the AD patients in the parieto-occipital area. It is assumed that the AD patients might use the neural compensational processes for the fixation state. This study provides evidence for the simultaneously EEG and eye-tracking changes in the areas, which are involved in the control of the fixational eye movements.