Investigating the effect of parasites (toxoplasma gondii RH strain, Leishmania major (MRHO/IR/75/ER), and hydatid cyst) antigens on Alzheimer's disease: An in vivo evaluation.

This study aimed to investigate the effects of parasite antigens on Alzheimer's symptoms in animal model. Alzheimer's model was induced in Wistar rats using Amyloid-beta peptide, and treated with parasite crude antigens from T. gondii RH strain, L. major (MRHO/IR/75/ER), and HC. Spectrophotometry and real-time PCR were used to evaluate the oxidative stress levels, antioxidant enzyme activity, and gene expression of NLRP3, IL-8, IL-1ß, and Caspase-1. Histological assays were performed to investigate structural changes in the hippocampus. Apoptosis was analyzed using an Annexin V Apoptosis by Flow cytometer. The levels of total oxidant, antioxidant, and SOD increased in the Alzheimer's group compared with the control group, but these factors were lower in the L. major group. The apoptosis in the treated groups was lower compared to the Alzheimer's group. IL-8 expression was significantly higher in all Alzheimer's groups, but decreased in the HC and L. major treated group compared to Alzheimer's. IL-1ß and Caspase-1 expression were similarly increased in all groups compared with the control group, but decreased in the antigen-treated groups compared with Alzheimer's. NLRP3 expression was increased in all groups compared with the control group, with lower expression in HC group, but significantly decreased in L. major group compared with Alzheimer's. In histological results, only L. major group could play a therapeutic role in pathological damage of the hippocampus. The results showed that parasite antigens, specifically L. major antigens, may have neuroprotective effects that reduce oxidative stress, apoptosis, and histopathological changes in response to AD in animal model.

Parkinson's disease tremor prediction using EEG data analysis-A preliminary and feasibility study.

PURPOSE: Tremor is one of the hallmarks of Parkinson's disease (PD) that does not respond effectively to conventional medications. In this regard, as a complementary solution, methods such as deep brain stimulation have been proposed. To apply the intervention with minimal side effects, it is necessary to predict tremor initiation. The purpose of the current study was to propose a novel methodology for predicting resting tremors using analysis of EEG time-series. METHODS: A modified algorithm for tremor onset detection from accelerometer data was proposed. Furthermore, a machine learning methodology for predicting PD hand tremors from EEG time-series was proposed. The most discriminative features extracted from EEG data based on statistical analyses and post-hoc tests were used to train the classifier for distinguishing pre-tremor conditions. RESULTS: Statistical analyses with post-hoc tests showed that features such as form factor and statistical features were the most discriminative features. Furthermore, limited numbers of EEG channels (F3, F7, P4, CP2, FC6, and C4) and EEG bands (Delta and Gamma) were sufficient for an accurate tremor prediction based on EEG data. Based on the selected feature set, a KNN classifier obtained the best pre-tremor prediction performance with an accuracy of 73.67%. CONCLUSION: This feasibility study was the first attempt to show the predicting ability of EEG time-series for PD hand tremor prediction. Considering the limitations of this study, future research with longer data, and different brain dynamics are needed for clinical applications.

The effects of AdipoRon on cytochrome P450-related gene expression, acute steroidogenic regulatory protein, and structure of ovary in polycystic ovary syndrome model.

PURPOSE: One of the most common causes of infertility in adult women is polycystic ovary syndrome (PCOS) which has been identified with symptoms such as chronic hyperandrogenism, anovulation, and polycystic ovaries. Adiponectin modulates steroidogenesis and the expression of ovulation-related genes. Herein, we assessed the effect of AdipoRon (adiponectin agonist) in the PCOS model mice. METHODS: The PCOS model was induced with letrozole in the adult female mice and the animals received intraperitoneal injection of AdipoRon (5 mg/kg) for 10 days. Expression of CYP11A, CYP17A, and CYP19A genes, StAR protein, and histomorphology of the ovary were evaluated using real-time RT-PCR, western blotting, and histochemistry methods, respectively. RESULTS: Although administration of letrozole caused an increase in the expression of CYP11A, CYP17A, and StAR and a decrease in the CYP19A1 expression, injection of AdipoRon reversed these changes. Moreover, AdipoRon treatment resulted in an improvement of folliculogenesis and a reduction of cysts compared to the letrozole-treated mice. CONCLUSION: It is likely that AdipoRon has protective effects on the PCOS through modulation of cytochrome P450-related genes and steroidogenesis but needs further study to be sure.

An inclusive study on cytokine gene expression in Parkinson's disease: Advanced analysis using Bayesian regression model.

BACKGROUND: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease throughout the globe whose specific pathophysiology is unknown. Researchers believe that inflammation and oxidative stress contribute to PD development. Also, alterations in cytokines production appear to have a key role in the pathogenesis of PD. The aim of the current study was to evaluate gene expression levels of nine cytokines in the peripheral blood of PD patients compared to a healthy control group. METHODS: Real-time PCR was used to analyze cytokines gene expression followed by advanced statistical analysis performed using Bayesian regression model in R (version 4.1.0) statistical software. RESULTS: TNF-α, IL-1ß, IL-2, IL-4, IFN-γ, IL-17 and IL-6 transcript levels were upregulated in patients compared to healthy controls. However, CXCL8 expression was downregulated in patients compared to controls and IFN-ß expression was not statistically different between the two groups. While we found no significant difference between the groups based on gender and age regarding TNF-α, IL-1ß, CXCL8, IL-2, IL-4, IFN-γ and IFN-ß gene expression, IL-6 and IL-17 transcript levels showed significant upregulations in older subjects and in females, respectively. In addition, we found that the interaction effects between gender and group on gene expression levels were not significant. In this way, the subgroup analysis within gender revealed that in each gender, expression levels of TNF-α, IL-2, IL-4, IL-6, IFN-γ and IL-17 were significantly higher in patients than controls. However, IFN-ß expression level did not show any significant difference between groups and subgroups. CONCLUSION: The present study provides evidence on significant alterations in cytokine expression with different patterns and points to immune system dysregulation in PD.

Therapeutic Effects of High-Intensity Interval Training Exercise Alone and Its Combination with Ecdysterone Against Amyloid Beta-Induced Rat Model of Alzheimer's Disease: A Behavioral, Biochemical, and Histological Study.

Hippocampal oxidative stress has a vital role in the pathophysiology of Alzheimer's disease (AD)-associated behavioral deficits. Ecdysterone (Ecdy), a natural product and primary steroid hormone, exhibits anti-oxidative and neuroprotective effects. High-intensity interval training (HIIT) has emerged as an effective method for improving physiological brain functions. The present study was designed to investigate the comparative effects of separate and combined HIIT and Ecdy treatment on behavioral functions, hippocampal oxidative status, histological changes in an amyloid-beta (Aß)-induced rat model of AD. Adult male rats were treated simultaneously with HIIT exercise and Ecdy (10 mg/kg/day; P.O.), starting ten days after Aß-injection, and they continued for eight consecutive weeks. At the end of the treatment course, the behavioral functions of the rats were assessed by commonly-used behavioral paradigms. Subsequently, brain samples were collected for histological analysis and hippocampus samples were collected for biochemical analysis. Results illustrated that Aß injection impaired learning and memory performances in both novel object recognition and Barnes maze tests, reduced exploratory/locomotor activities in open field test, enhanced anxiety-like behavior in elevated plus-maze (P < 0.05). These behavioral deficits accompanied hippocampal oxidative stress (decreased total antioxidant capacity content and glutathione peroxidase enzyme activity, increased total oxidant status and malondialdehyde level) and neuronal loss in the cerebral cortex and hippocampus in H&E staining (P < 0.05). HIIT and Ecdy improved anxiety-like behavior, attenuated total oxidant status and malondialdehyde, and prevented the neuronal loss (P < 0.05). However, their combination resulted in a more complete and powerful improvement in all the above-mentioned Aß-related deficits (P < 0.05). Overall, these data provide evidence that a combination of HIIT and Ecdy treatment improves Aß-induced behavioral deficits, possibly through ameliorating hippocampal oxidative status and preventing neuronal loss.

Effects of the combination of high-intensity interval training and Ecdysterone on learning and memory abilities, antioxidant enzyme activities, and neuronal population in an Amyloid-beta-induced rat model of Alzheimer's disease.

AIMS: Oxidative stress and neuronal death are the primary reasons for the progression of amyloid-beta (Aß) deposition and cognitive deficits in Alzheimer's disease (AD). Ecdysterone (ecdy), a common derivative of ecdysteroids, possesses free radical scavenging and cognitive-improving effects. High-intensity interval training (HIIT) can be a therapeutic strategy for improving cognitive decline and oxidative stress. The present study was aimed to evaluate the effect of HIIT exercise and ecdy consumption synergistically on the changes in learning and memory functions, activities of hippocampal antioxidant enzymes, and neuronal population after AD induced by Aß in male rats. MATERIALS AND METHODS: Following ten days of Aß injection, HIIT exercise and ecdy treatment (10 mg/kg/day; P.O.) were initiated and continued for eight consecutive weeks in rats. At the end of the treatment period, the rat's learning and memory functions were assessed using Morris water maze and passive avoidance tests. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GRx), and changes in neuronal population were evaluated in rats' brains. RESULTS: The results indicated that Aß injection disrupted spatial/passive avoidance learning and memory in both tests, accompanied by a decrease in the SOD and CAT (as endogenous antioxidants) in rats' hippocampus. Additionally, Aß injection resulted in neuronal loss in the cerebral cortex and hippocampus. Although the consumption of ecdy separately improved spatial/passive avoidance learning and memory impairments, recovered hippocampal activity of SOD, CAT, GRx, and prevented the hippocampal neuronal loss, its combination along with HIIT resulted in a more powerful and effective amelioration in all the above-mentioned Aß-neuropathological changes. CONCLUSION: Our results confirm that a combination of HIIT and ecdy treatment could be a promising potential therapeutic option against AD-associated cognitive decline, owing to their free radical scavenging and neuroprotective properties.

Over-expression of IL-6 coding gene in the peripheral blood of migraine with aura patients.

Migraine is a common disorder which is placed among the top ten reasons of years lived with disability. Cytokines are among the molecules that contribute in the pathophysiology of migraine. In the current study, we evaluated expression levels of IL-6 coding gene in the peripheral blood of 120 migraine patients (54 migraine without aura and 66 migraine with aura patients) and 40 healthy subjects. No significant difference was detected in expression of IL-6 between total migraine patients and healthy controls (Posterior beta = 0.253, P value = 0.199). The interaction effect between gender and group was significant (Posterior beta =-1.274, P value = 0.011), therefore, we conducted subgroup analysis within gender group. Such analysis revealed that while expression of this gene is not different between male patients and male controls (Posterior beta =-0.371, P value > 0.999), it was significantly over-expressed in female patients compared with female controls (Posterior beta = 0.86, P= 0.002). Expression of IL-6 was significantly higher in patients with aura compared with controls (Posterior beta = 0.63, adjusted P value = 0.019). However, expression of this cytokine coding gene was not different between patients without aura and healthy subjects (Posterior beta = 0.193, adjusted P value = 0.281). Therefore, IL-6 might be involved in the pathophysiology of migraine among females and migraine with aura among both sexes.

Accelerating gas-liquid chemical reactions in flow.

Over the past decade, continuous flow reactors have emerged as a powerful tool for accelerated fundamental and applied studies of gas-liquid reactions, offering facile gas delivery and process intensification. In particular, unique features of highly gas-permeable tubular membranes in flow reactors (i.e., tube-in-tube flow reactor configuration) have been exploited as (i) an efficient analytic tool for gas-liquid solubility and diffusivity measurements and (ii) reliable gas delivery/generation strategy, providing versatile adaptability for a wide range of gas-liquid processes. The tube-in-tube flow reactors have been successfully adopted for rapid exploration of a wide range of gas-liquid reactions (e.g., amination, carboxylation, carbonylation, hydrogenation, ethylenation, oxygenation) using gaseous species both as the reactant and the product, safely handling toxic and flammable gases or unstable intermediate compounds. In this highlight, we present an overview of recent developments in the utilization of such intensified flow reactors within modular flow chemistry platforms for different gas-liquid processes involving carbon dioxide, oxygen, and other gases. We provide a detailed step-by-step guideline for robust assembly and safe operation of tube-in-tube flow reactors. We also discuss the current challenges and potential future directions for further development and utilization of tubular membrane-based flow reactors for gas-liquid processes.

Therapeutic effects of melatonin-treated bone marrow mesenchymal stem cells (BMSC) in a rat model of Alzheimer's disease.

The therapy based on mesenchymal stem cells(MSCs) has received growing attraction for Alzheimer's disease(AD). However, a great challenge in this regard is the low survival rate of MSCs following transplantation. This study seeks to improve the therapy based on Bone Marrow MSCs (BM-MSCs) through melatonin (MT) pre-treatment, which is 'a known antioxidant' in an animal model of AD. In this paper, we separated BMSCs from the rat tibia and femur bones and then pretreated cells were with 5µM of MT for 24 h.The sample consisted of 40 male Wistar rats randomly assigned to the control, sham,MT-pretreated BMSCs and amyloid-beta (Aß) peptide BMSCs groups.Two months after the cell transplantation,a number of tests including novel object recognition, Morris water maze, passive avoidance test, and open field test were undertaken. 69 days after the cell therapy,the rats were sacrificed.We removed brain tissues histopathological analysis and carried out immunohistochemistry for Beta tubulin, GFAP and iba1 proteins.The results suggested that both MT-BMSCs and BMSCs moved to brain tissues following the intravenous transplantation.However,MT-BMSCs had a significant effect on boosting learning, cognition and memory in comparison with BMSCs (P < 0.05). Furthermore, there was a significant rise in GFAP and Beta tubulin and substantial fall in microglial cells in the BMSCs in comparison with MT-BMSCs.Stem cell therapy has been proposed as an effective strategy for neurodegenerative diseases,but its therapeutic features are restricted.It has been shown that the pretreatment of MSCs with melatonin partly would boost cells efficiency and thereby alleviate AD complications such as memory and cognition.

Vitrification and in vitro culture had no adverse effect on the follicular development and gene expression of stimulated human ovarian tissue.

AIM: The study assesses the effect of the vitrification procedure on the integrity, morphology, follicular development and gene expression of stimulated human ovarian tissue after warming and two weeks of in vitro culture. METHODS: Ovarian specimens were divided into non-vitrified and vitrified groups and were cultured for two weeks. Morphological analysis and immunohistochemistry were performed. The 17-ß estradiol and anti-Müllerian hormone levels in collected media were assessed. Gene expression was analyzed using real-time reverse transcription polymerase chain reaction. RESULTS: The morphology and immunohistochemistry of bcl-2-like protein 4 and B-cell lymphoma 2 of human stimulated ovarian tissue were similar in both groups. There was no significant difference in the percentage of normal follicles between the groups before and after in vitro culture. In spite of an increase in the percentage of growing follicles in cultured tissues compared to the non-cultured groups, the rate of normal follicles was significantly decreased in both cultured groups (P < 0.05). Gene expression was no different in vitrified tissues compared to the control; however, the expression of growth differentiation factor 9 and follicle stimulating hormone receptor genes were increased and factor in germ line alpha and kit ligand genes were decreased during in vitro culture (P < 0.05). In the two cultured groups, the level of 17-ß estradiol was increased (P < 0.05), but the anti-Müllerian hormone concentration was not statistically altered. CONCLUSIONS: These results showed that the integrity of stimulated human ovarian tissue after vitrification/warming was well preserved; however, the in vitro culture condition needs improvement.

Learning-Based Multi-Label Segmentation of Transrectal Ultrasound Images for Prostate Brachytherapy.

Low-dose-rate prostate brachytherapy treatment takes place by implantation of small radioactive seeds in and sometimes adjacent to the prostate gland. A patient specific target anatomy for seed placement is usually determined by contouring a set of collected transrectal ultrasound images prior to implantation. Standard-of-care in prostate brachytherapy is to delineate the clinical target anatomy, which closely follows the real prostate boundary. Subsequently, the boundary is dilated with respect to the clinical guidelines to determine a planning target volume. Manual contouring of these two anatomical targets is a tedious task with relatively high observer variability. In this work, we aim to reduce the segmentation variability and planning time by proposing an efficient learning-based multi-label segmentation algorithm. We incorporate a sparse representation approach in our methodology to learn a dictionary of sparse joint elements consisting of images, and clinical and planning target volume segmentation. The generated dictionary inherently captures the relationships among elements, which also incorporates the institutional clinical guidelines. The proposed multi-label segmentation method is evaluated on a dataset of 590 brachytherapy treatment records by 5-fold cross validation. We show clinically acceptable instantaneous segmentation results for both target volumes.

Ultrasound-Based Characterization of Prostate Cancer Using Joint Independent Component Analysis.

OBJECTIVE: This paper presents the results of a new approach for selection of RF time series features based on joint independent component analysis for in vivo characterization of prostate cancer. METHODS: We project three sets of RF time series features extracted from the spectrum, fractal dimension, and the wavelet transform of the ultrasound RF data on a space spanned by five joint independent components. Then, we demonstrate that the obtained mixing coefficients from a group of patients can be used to train a classifier, which can be applied to characterize cancerous regions of a test patient. RESULTS: In a leave-one-patient-out cross validation, an area under receiver operating characteristic curve of 0.93 and classification accuracy of 84% are achieved. CONCLUSION: Ultrasound RF time series can be used to accurately characterize prostate cancer, in vivo without the need for exhaustive search in the feature space. SIGNIFICANCE: We use joint independent component analysis for systematic fusion of multiple sets of RF time series features, within a machine learning framework, to characterize PCa in an in vivo study.

Fusion analysis of first episode depression: where brain shape deformations meet local composition of tissue.

Computational neuroanatomical techniques that are used to evaluate the structural correlates of disorders in the brain typically measure regional differences in gray matter or white matter, or measure regional differences in the deformation fields required to warp individual datasets to a standard space. Our aim in this study was to combine measurements of regional tissue composition and of deformations in order to characterize a particular brain disorder (here, major depressive disorder). We use structural Magnetic Resonance Imaging (MRI) data from young adults in a first episode of depression, and from an age- and sex-matched group of non-depressed individuals, and create population gray matter (GM) and white matter (WM) tissue average templates using DARTEL groupwise registration. We obtained GM and WM tissue maps in the template space, along with the deformation fields required to co-register the DARTEL template and the GM and WM maps in the population. These three features, reflecting tissue composition and shape of the brain, were used within a joint independent-components analysis (jICA) to extract spatially independent joint sources and their corresponding modulation profiles. Coefficients of the modulation profiles were used to capture differences between depressed and non-depressed groups. The combination of hippocampal shape deformations and local composition of tissue (but neither shape nor local composition of tissue alone) was shown to discriminate reliably between individuals in a first episode of depression and healthy controls, suggesting that brain structural differences between depressed and non-depressed individuals do not simply reflect chronicity of the disorder but are there from the very outset.

Fusion analysis of functional MRI data for classification of individuals based on patterns of activation.

Classification of individuals based on patterns of brain activity observed in functional MRI contrasts may be helpful for diagnosis of neurological disorders. Prior work for classification based on these patterns have primarily focused on using a single contrast, which does not take advantage of complementary information that may be available in multiple contrasts. Where multiple contrasts are used, the objective has been only to identify the joint, distinct brain activity patterns that differ between groups of subjects; not to use the information to classify individuals. Here, we use joint Independent Component Analysis (jICA) within a Support Vector Machine (SVM) classification method, and take advantage of the relative contribution of activation patterns generated from multiple fMRI contrasts to improve classification accuracy. Young (age: 19-26) and older (age: 57-73) adults (16 each) were scanned while listening to noise alone and to speech degraded with noise, half of which contained meaningful context that could be used to enhance intelligibility. Functional contrasts based on these conditions (and a silent baseline condition) were used within jICA to generate spatially independent joint activation sources and their corresponding modulation profiles. Modulation profiles were used within a non-linear SVM framework to classify individuals as young or older. Results demonstrate that a combination of activation maps across the multiple contrasts yielded an area under ROC curve of 0.86, superior to classification resulting from individual contrasts. Moreover, class separability, measured by a divergence criterion, was substantially higher when using the combination of activation maps.

Temporal-lobe morphology differs between healthy adolescents and those with early-onset of depression.

Major depressive disorder (MDD) has previously been linked to structural changes in several brain regions, particularly in the medial temporal lobes (Bellani, Baiano, Brambilla, 2010; Bellani, Baiano, Brambilla, 2011). This has been determined using voxel-based morphometry, segmentation algorithms, and analysis of shape deformations (Bell-McGinty et al., 2002; Bergouignan et al., 2009; Posener et al., 2003; Vasic et al., 2008; Zhao et al., 2008): these are methods in which information related to the shape and the pose (the size, and anatomical position and orientation) of structures is lost. Here, we incorporate information about shape and pose to measure structural deformation in adolescents and young adults with and without depression (as measured using the Beck Depression Inventory and Diagnostic and Statistical Manual of Mental Disorders criteria). As a hypothesis-generating study, a significance level of p < 0.05, uncorrected for multiple comparisons, was used, so that subtle morphological differences in brain structures between adolescent depressed individuals and control participants could be identified. We focus on changes in cortical and subcortical temporal structures, and use a multi-object statistical pose and shape model to analyze imaging data from 16 females (aged 16-21) and 3 males (aged 18) with early-onset MDD, and 25 female and 1 male normal control participants, drawn from the same age range. The hippocampus, parahippocampal gyrus, putamen, and superior, inferior and middle temporal gyri in both hemispheres of the brain were automatically segmented using the LONI Probabilistic Brain Atlas (Shattuck et al., 2008) in MNI space. Points on the surface of each structure in the atlas were extracted and warped to each participant's structural MRI. These surface points were analyzed to extract the pose and shape features. Pose differences were detected between the two groups, particularly in the left and right putamina, right hippocampus, and left and right inferior temporal gyri. Shape differences were detected between the two groups, particularly in the left hippocampus and in the left and right parahippocampal gyri. Furthermore, pose measures were significantly correlated with BDI score across the whole (clinical and control) sample. Since the clinical participants were experiencing their very first episodes of MDD, morphological alteration in the medial temporal lobe appears to be an early sign of MDD, and is unlikely to result from treatment with antidepressants. Pose and shape measures of morphology, which are not usually analyzed in neuromorphometric studies, appear to be sensitive to depressive symptomatology.

Automatic localization of the da Vinci surgical instrument tips in 3-D transrectal ultrasound.

Robot-assisted laparoscopic radical prostatectomy (RALRP) using the da Vinci surgical system is the current state-of-the-art treatment option for clinically confined prostate cancer. Given the limited field of view of the surgical site in RALRP, several groups have proposed the integration of transrectal ultrasound (TRUS) imaging in the surgical workflow to assist with accurate resection of the prostate and the sparing of the neurovascular bundles (NVBs). We previously introduced a robotic TRUS manipulator and a method for automatically tracking da Vinci surgical instruments with the TRUS imaging plane, in order to facilitate the integration of intraoperative TRUS in RALRP. Rapid and automatic registration of the kinematic frames of the da Vinci surgical system and the robotic TRUS probe manipulator is a critical component of the instrument tracking system. In this paper, we propose a fully automatic registration technique based on automatic 3-D TRUS localization of robot instrument tips pressed against the air-tissue boundary anterior to the prostate. The detection approach uses a multiscale filtering technique to identify and localize surgical instrument tips in the TRUS volume, and could also be used to detect other surface fiducials in 3-D ultrasound. Experiments have been performed using a tissue phantom and two ex vivo tissue samples to show the feasibility of the proposed methods. Also, an initial in vivo evaluation of the system has been carried out on a live anaesthetized dog with a da Vinci Si surgical system and a target registration error (defined as the root mean square distance of corresponding points after registration) of 2.68 mm has been achieved. Results show this method's accuracy and consistency for automatic registration of TRUS images to the da Vinci surgical system.