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    Neuroinflammation in Autism and Supplementation Based on Omega-3 Polyunsaturated Fatty Acids: A Narrative Review

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    Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction across multiple contexts and restricted, repetitive patterns of behavior, interests and activities. The maternal status of polyunsaturated fatty acids (PUFA) regulates microglial activity and neuroinflammatory pathways during a child’s brain development. In children with ASD, the metabolism of PUFA is thought to be deficient or abnormal, leading to increased production of proinflammatory cytokines, increased oxidative stress and an imbalance in the formation and action of neurotransmitters. In addition, nutritional deficits in omega-3 PUFA may affect gut microbiota and contribute to ASD by the gut–brain axis. The aim of this study was to review the possible role of neuroinflammation in ASD development and the effect of omega-3 PUFA supplementation in children with ASD. Due to a wide heterogeneity across RCTs, no definitive conclusion about omega-3 PUFA effects in ASD can be drawn. Supplementation with PUFA could be considered as one of the aspects in regulating the biological status of the organism and could provide added value to standard medical and psychological interventions for reducing behavioral deficits

    The effects of incubation media on the assessment of the shape of human erythrocytes by flow cytometry: a contribution to mathematical data interpretation to enable wider application of the method

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    Flow cytometry (FC) analysis of erythrocyte shape and related biomechanical properties, such as osmotic fragility, have not moved from a research tool to regular clinical testing. The main reason is existing evidence that various pre-analytical factors influence the mathematical interpretation of the data obtained. With an aim to contribute to the standardization and broaden the use of FC for human erythrocyte shape assessment, freshly prepared peripheral blood erythrocytes isolated from healthy donors were incubated in iso and hypo-osmotic solutions (pure saline, saline with potassium and calcium, and phosphate buffered saline) and examined by FC using values of forward scatter (FSC) and side scatter (SSC). Kurtosis, skewness, Pearson's second skewness coefficient of dissymmetry (PCD), and spherical index, calculated from FSC distributions, were used for the erythrocyte shape evaluation. In all isotonic media FSC distribution and FSC-based morphology parameters showed huge inter-individual and inter-medium variation. With decreasing osmolality, in all media and samples, the size of the erythrocytes increased, and swelling index and kurtosis decreased. However, changes in skewness and PCD were influenced by the medium used and the sample tested. Compared to FSC, SSC signal in isotonic and its change in hypotonic media showed lower inter-individual variation and was not influenced by the type of medium. We propose a spherical index and kurtosis as FSC-based indicators of erythrocyte shape. As more resistant to the influence of the preanalytical treatment, SSC data appeared to be unfairly neglected for the assessment of erythrocyte shape, in comparison to the usually employed FSC data

    Exploring immunogenicity of tick salivary AV422 protein in persons exposed to ticks: prospects for utilization

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    In order to determine whether conserved tick salivary protein AV422 is immunogenic, the goal of our study was to detect specific IgG response within at-risk populations. Study groups included 76 individuals, differing in occurrence of recently recorded tick bites and health status. Western blotting with recombinant (r) protein derived from Ixodes ricinus (Ir) was performed. IgG response to Borrelia/Rickettsia, as indicators of previous tick infestations, was also assessed. Additionally, a detailed in silico AV422 protein sequence analysis was performed, followed by modelling of the interactions between peptides and corresponding MHC II molecules by molecular docking. Anti-rIrAV422 seroprevalences among individuals exposed to ticks were high (62.5, 57.9 and 66.7%) and anti-Borrelia/Rickettsia seroprevalences were 54.2, 15.8 and 44.4% among individuals with/without recent tick bite and patients suspected of tick-borne disease, respectively. In silico analysis of AV422 protein sequence showed a high level of conservation across tick genera, including also the predicted antigenic determinants specific for T and B cells. Docking to the restricted MHC II molecules was performed for all predicted AV422 T cell epitopes, and the most potent (highly immunogenic) epitope determinants were suggested. The epitope prediction reveals that tick salivary protein AV422 may elicit humoral immune response in humans, which is consistent with the high anti-rIrAV422 seroprevalence in tested at-risk subjects. Tick-borne diseases are a growing public health concern worldwide, and AV422 is potentially useful in clinical practice and epidemiological studies

    Dental mesenchymal stromal/stem cells in different microenvironments — implications in regenerative therapy

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    Current research data reveal microenvironment as a significant modifier of physical functions, pathologic changes, as well as the therapeutic effects of stem cells. When comparing regeneration potential of various stem cell types used for cytotherapy and tissue engineering, mesenchymal stem cells (MSCs) are currently the most attractive cell source for bone and tooth regeneration due to their differentiation and immunomodulatory potential and lack of ethical issues associated with their use. The microenvironment of donors and recipients selected in cytotherapy plays a crucial role in regenerative potential of transplanted MSCs, indicating interactions of cells with their microenvironment indispensable in MSC-mediated bone and dental regeneration. Since a variety of MSC populations have been procured from different parts of the tooth and tooth-supporting tissues, MSCs of dental origin and their achievements in capacity to reconstitute various dental tissues have gained attention of many research groups over the years. This review discusses recent advances in comparative analyses of dental MSC regeneration potential with regards to their tissue origin and specific microenvironmental conditions, giving additional insight into the current clinical application of these cells

    Morphological, fractal, and textural features for the blood cell classification: the case of acute myeloid leukemia

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    Microscopic examination of stained peripheral blood smears is, nowadays, an indispensable tool in the evaluation of patients with hematological and non-hematological diseases. While a rapid automated quantification of the regular blood cells is available, recognition and counting of immature white blood cells (WBC) still relies mostly on the microscopic examination of blood smears by an experienced observer. Recently, there are efforts to improve the prediction by various machine learning approaches. An open dataset collection including the recently digitalized single-cell images for 200 patients, from peripheral blood smears at 100 × magnification, was used. We studied different morphological, fractal, and textural descriptors for WBC classification, with an aim to indicate the most reliable parameters for the recognition of certain cell types. Structural properties of both the mature and non-mature leukocytes obtained from (i) acute myeloid leukemia patients, or (ii) non-malignant controls, were studied in depth, with a sample size of about 25 WBC per group. We quantified structural and textural differences and, based on the statistical ranges of parameters for different WBC types, selected eight features for classification: Cell area, Nucleus-to-cell ratio, Nucleus solidity, Fractal dimension, Correlation, Contrast, Homogeneity, and Energy. Classification Precision of up to 100% (80% on average) was achieved

    Fatty acid in colorectal cancer in adult and aged patients of both sexes

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    Purpose: Colorectal cancer represents the second most common type of cancer in Serbia. Alteration of lipid metabolism begins early, and can represent a central hallmark in cancer evolution. Fatty acids have various important functions as building components of cell membranes, as signaling molecules in immune responses and also manage the general cancer signaling network. The purpose of this study was to investigate the difference of various fatty acids content between colorectal cancer and adjacent healthy intestinal tissue in adult and aged patients of both sexes. Methods: 52 subjects participated in this study. Healthy colon mucosa and tumor tissue samples were obtained from patients previously diagnosed with colorectal carcinoma. Simplified method of Berstad et al was used for direct transesterification of total lipids in tumor and healthy mucosa tissue samples and separations of the methyl esters was carried out using a gas chromatograph equipped with a split/ splitless injector and a flame ionization detector. Results: 18 0, 18 1 n7, 20 3, 20 4, 20 5, 22 4, 22 5 22 6, SFA, PUFA, n6, n3 and AA/EPA were significantly higher in tumor tissue. On the other hand, 18 1 n9, 18 2, 18 3 n3, MUFA, n6/ n3 were significantly higher in healthy tissue. Conclusions: Saturation index (SI) could be a valuable tool to delineate robust immune response and worse prognosis in patients with colorectal cancer. Our study demonstrated significant differences in fatty acid profiles between tumor tissue and healthy mucosa. Parameters, such as gender, age, stage and mucinous component didn't influence altered fatty acid content

    Dietary Zn deficiency, the current situation, and potential solutions

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    Zinc (Zn) deficiency is a world-wide problem and this review presents an overview of the magnitude of Zn deficiency with a particular emphasis on present global challenges, current recommendations for Zn intake, and factors that affect - dietary requirements. The challenges of monitoring Zn status are clarified together with the discussion of relevant Zn bioaccessibility and bioavailability issues. Modern lifestyle factors that may exacerbate Zn deficiency and new strategies of reducing its effects are presented. Biofortification, as a potentially useful strategy for improving Zn status in sensitive populations, has been discussed. The review proposes potential actions that could deliver promising results both in terms of monitoring dietary and physiological Zn status as well as in alleviating dietary Zn deficiency in affected populations.This is the peer-reviewed version of the article: Knez, M.; Stangoulis, J. C. R. Dietary Zn Deficiency, the Current Situation, and Potential Solutions. Nutrition Research Reviews 2021, 1–44, [https://doi.org/10.1017/S0954422421000342

    Gamma-Range Auditory Steady-State Responses and Cognitive Performance: A Systematic Review

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    The auditory steady-state response (ASSR) is a result of entrainment of the brain's oscillatory activity to the frequency and phase of temporally modulated stimuli. Gamma-range ASSRs are utilized to observe the dysfunctions of brain-synchronization abilities in neuropsychiatric and developmental disorders with cognitive symptoms. However, the link between gamma-range ASSRs and cognitive functioning is not clear. We systematically reviewed existing findings on the associations between gamma-range ASSRs and cognitive functions in patients with neuropsychiatric or developmental disorders and healthy subjects. The literature search yielded 1597 articles. After excluding duplicates and assessing eligibility, 22 articles were included. In healthy participants, the gamma-range ASSR was related to cognitive flexibility and reasoning as measured by complex tasks and behavioral indicators of processing speed. In patients with schizophrenia, the studies that reported correlations found a higher ASSR to be accompanied by better performance on short-term memory tasks, long-term/semantic memory, and simple speeded tasks. The main findings indicate that individual differences in the gamma-range ASSR reflect the level of attentional control and the ability to temporary store and manipulate the information, which are necessary for a wide range of complex cognitive activities, including language, in both healthy and impaired populations

    Novi derivati 4-aminohinolina kao umereni inhibitori parazita

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    Synthesis of novel aminoquinoline derivatives has been accomplished and their activity against malaria strains has been examined. The compounds showed moderate in vitro antimalarial activity against two P. falciparum strains, 3D7 (CQ susceptible clone) and Dd2 (CQ resistant clone). Three aminoquinolines were further examined for antimalarial efficacy in a mouse model using a modified Thompson test. In this model, mice were infected with P. berghei-infected red blood cells, and drugs were administered orally. Antimalarial 3 was found toxic at a dose of 320 (mg/kg)/day in 3/6 mice, however, 2/6 mice of the same group survived through day 31, and one of them was cured

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