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الملخص: اهداف البحث: يدرس هذه البحث مضادات الأكسدة، ونشاط مضادات الميكروبات والتركيب الكيميائي للزيت الأساسي الذي تم عزله من الأجزاء الهوائية لحمض أورانتيفوليا. طرق البحث: تم جمع الأوراق الطازجة لحمض أورانتيفوليا من مزارع محلية في مدينة صور (المنطقة الشرقية) لسلطنة عمان خلال الفترة من يونيو- يوليو، ٢٠١٥. استخدمت طريقة التقطير المائي لعزل الزيت الأساسي. واستخدم الغاز اللوني- قياس الطيف الكتلي للتعرف ولتحديد كمية المكونات الكيمائية في الزيت. استخدمت طريقة الجرف الحرة للجذور في – المختبر لتحديد نشاط مضادات الأكسدة للزيت الذي تم عزله من أوراق الليمون، بينما تم تقييم النشاط المضاد للجراثيم ضد البكتيريا إيجابية الغرام والبكتيريا سلبية الغرام بطريقة انتشار القرص. النتائج: تم تحديد ما مجموعة ثلاثة وثلاثين مركبا كيميائيا وتم العثور على د- ليمونين (٦٣.٣٥٪) ليكون المكون الأساسي. تم تحديد مكونات رئيسة أخرى بنسب مختلفة. كما أظهر الزيت الأساسي لحمض أورانتيفوليا نشاطا ممتازا مضادا للجراثيم ضد المكورات العنقودية الذهبية ونشاط متوسطا ضد السلالات الإشريكية القولونية. وأظهر الزيت كذلك نشاطا واعدا لمضادات الأكسدة في المختبر ولكنه أظهر نشاطا مضادا للجراثيم متوسطا. الاستنتاجات: يتميز الزيت الأساسي لأوراق الليمون العماني بمحتوى عالي من د- ليمونين الذي يجعله مفيدا في الغذاء، والصناعات الدوائية والعطور. Abstract: Objectives: This study investigated the chemical composition and the antioxidant and antimicrobial activities of the essential oil isolated from the aerial parts of Citrus aurantifolia L. Methods: Fresh Citrus aurantifolia L. leaves were collected from farms in Sur city, located in the Al-Sharqia (Eastern) region of the Sultanate of Oman, during June–July of 2015. The essential oil was isolated using hydrodistillation. Gas chromatography–mass spectrometry (GC–MS) was used to identify and quantify the chemical constituents of the oil. An in-vitro 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging method was used to determine the antioxidant activity of the isolated oil from the lime leaves while a disc diffusion method was used to evaluate the antibacterial activity against Gram-negative and Gram-positive bacteria. Results: Thirty-three chemical compounds were identified, with d-limonene (63.35%) forming the major constituent. Other prominent constituents include 3,7-dimethyl-2,6-octadien-1-ol (7.07%), geraniol (6.23%), E-citral (4.35%), Z-citral (3.29%), and β-ocimene (2.25%). The essential oil of Citrus aurantifolia L. leaves showed excellent antibacterial activity against Staphylococcus aureus and moderate activity against pathogenic Escherichia coli strains. The oil exhibited promising in-vitro antioxidant activity (IC50 value = 21.57 μg/mL) but showed moderate antibacterial activities. Conclusions: The essential oil from Omani lime leaves is characterized by a high d-limonene content, making it useful for food, pharmaceutical, and perfumery industries. الكلمات المفتاحية: النشاط المضاد للجراثيم, حمض أورانتيفوليا, الزيت الأساسي, د- ليمونين, Keywords: Antibacterial activity, Citrus aurantifolia, d-limonene, Essential oil, GC–MS

Under physiological conditions the gut-associated lymphoid tissues not only prevent the induction of a local inflammatory immune response, but also induce systemic tolerance to fed antigens (1,2). A notable exception is coeliac disease, where genetically susceptible individuals expressing human leukocyte antigen (HLA) HLA-DQ2 or HLA-DQ8 molecules develop inflammatory T-cell and antibody responses against dietary gluten, a protein present in wheat (3). The mechanisms underlying this dysregulated mucosal immune response to a soluble antigen have not been identified. Retinoic acid, a metabolite of vitamin A, has been shown to have a critical role in the induction of intestinal regulatory responses (4-6). Here we find in mice that in conjunction with IL-15, a cytokine greatly upregulated in the gut of coeliac disease patients (3,7), retinoic acid rapidly activates dendritic cells to induce JNK (also known as MAPK8) phosphorylation and release the proinflammatory cytokines IL-12p70 and IL-23. As a result, in a stressed intestinal environment, retinoic acid acted as an adjuvant that promoted rather than prevented inflammatory cellular and humoral responses to fed antigen. Altogether, these findings reveal an unexpected role for retinoic acid and IL-15 in the abrogation of tolerance to dietary antigens., Induction of regulatory intestinal responses to oral antigens prevents the subsequent development of systemic T-helper type-1 ([T.sub.H]1) responses to those antigens, a phenomenon referred to as oral tolerance (2). An [...]

Understanding the initiation of T-helper (Th)-2 immunity is crucial for addressing allergic diseases that have been linked to the commensal microbiota. However, Th2 responses are notably absent from known host-microbiota intestinal immune circuits. Notably, the commensal protist Tritrichomonas induces a transient innate ILC2 circuit rather than a chronic Th2 circuit. Canonical Th2 responses rely on the induction of IL-4 production by innate cells. This study shows that the absence of Tet2 , a DNA demethylase, reprograms naïve T cells to autonomously produce IL-4 upon T cell receptor stimulation, bypassing the need for IL-4 from innate cells for Th2 differentiation. Loss of this checkpoint induces chronic Th2 responses to Tritrichomonas , associated with IL-25-dependent barrier dysfunction and increased susceptibility to allergic pathology in response to dietary antigens., Sentence Summary: Regulation of cell autonomous IL-4 in T cells is critical to prevent dysregulated Th2 immunity to commensals and predisposition to allergy.

Aim: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by unique behavioral patterns, treating children with ASD in the dental clinic has been a great challenge due to their behavior. This study aims to determine the effectiveness of culturally adapted dental visual aids in modifying behavior patterns during dental visits in children with ASD., Materials and Methods: A controlled, blinded, randomized, clinical trial, with 64 children diagnosed with ASD, were randomly divided into two groups. The study took place between January 2019 and January 2021. The experimental group was provided with culturally adapted dental visual aids created especially for this research and the control group was provided with universal dental visual aids. The children's behavior patterns were evaluated before and after using the dental visual aids. SPSS v.25 was used to process all the data., Results: Behavior patterns have modified significantly in the experimental group ( p < 0.001) however, it was statistically insignificant in the control group ( p = 0.077). In terms of behavioral patterns, the experimental group outperformed the control group significantly ( p < 0.001)., Conclusion: The culturally adapted dental visual aids have shown effectiveness in modifying behavior patterns in children diagnosed with ASD during dental visits., Clinical Significance: By evaluating the impact of culturally adapted visual aids on behavior management, the study can enhance the accessibility and effectiveness of dental care for this vulnerable population, ultimately promoting better oral health outcomes and reducing potential trauma associated with dental visits for children with ASD. How to cite this article: Aljubour AA, AbdElBaki M, El Meligy O, et al . Culturally Adapted Dental Visual Aids Effect on Behavior Management during Dental Visits in Children with Autism Spectrum Disorder. J Contemp Dent Pract 2024;25(1):20-28.

All nucleated cells express major histocompatibility complex I and interferon-γ (IFNγ) receptor 1 , but an epithelial cell-specific function of IFNγ signalling or antigen presentation by means of major histocompatibility complex I has not been explored. We show here that on sensing IFNγ, colonic epithelial cells productively present pathogen and self-derived antigens to cognate intra-epithelial T cells, which are critically located at the epithelial barrier. Antigen presentation by the epithelial cells confers extracellular ATPase expression in cognate intra-epithelial T cells, which limits the accumulation of extracellular adenosine triphosphate and consequent activation of the NLRP3 inflammasome in tissue macrophages. By contrast, antigen presentation by the tissue macrophages alongside inflammasome-associated interleukin-1α and interleukin-1β production promotes a pathogenic transformation of CD4 + T cells into granulocyte-macrophage colony-stimulating-factor (GM-CSF)-producing T cells in vivo, which promotes colitis and colorectal cancer. Taken together, our study unravels critical checkpoints requiring IFNγ sensing and antigen presentation by epithelial cells that control the development of pathogenic CD4 + T cell responses in vivo., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) have an increased risk of developing colorectal neoplasia (CRN) in the proximal colon., Objectives: To evaluate whether duration and severity of inflammation are linked to the development of CRN in this population., Design: Retrospective, case-control chart review of patients with PSC and IBD at a tertiary care center., Methods: Disease activity was scored per colonic segment at each colonoscopy prior to the first instance of observed CRN using a modified Mayo endoscopic sub-score and histologic assessment. Patients in the CRN-positive group were compared to controls that did not., Results: In all, 72 PSC-IBD patients with no history of CRN were identified, 13 of whom developed CRN after at least one colonoscopy at our institution. Patients in the CRN-positive group had significantly more endoscopic ( p  < 0.01) and histologic ( p  < 0.01) inflammation in the right compared to the control group prior to the development of dysplasia. There was significantly greater endoscopic inflammation in the segment of the colon with a dysplastic lesion than other segments of the colon ( p  = 0.018). Patients with moderate/severe lifetime endoscopic ( p  = 0.02) or histologic inflammation ( p  = 0.04) score had a lower probability of remaining free of dysplasia during follow-up. Nearly half of the patients with dysplasia had invisible lesions found on random biopsy., Conclusions: Endoscopic and histologic inflammation in the proximal colon are risk factors for CRN in patients with PSC-IBD. PSC-IBD patients frequently have subclinical inflammation, and these findings support the practice of regular assessment of disease activity and random biopsy of inflamed and uninflamed areas in patients with PSC with the goal of reducing inflammation to prevent the development of CRN., Competing Interests: OKJ, DS, ZD, ND, NF, SK, NK, AS, CRW, SD, BJ, and JP report no relevant conflicts of interest. RDC reports consulting for Abbvie Laboratories, BMS/Celgene, Eli Lilly, Genentech, Gilead Sciences, Hoffmann La-Roche, Janssen, Pfizer, Takeda, and UCB Pharma; and engaging in clinical trials/receiving grant support from, Abbvie, BMS/Celgene, Boehringer Ingelheim, Crohn’s & Colitis Foundation of America, Genentech, Gilead Sciences, Hollister, Medimmune, Mesoblast Ltd., Osiris Therapeutics, Pfizer, Receptos, RedHill Biopharma, Sanofi-Aventis, Schwarz Pharma, Seres Therapeutics, Takeda Pharma, UCB Pharma; DTR reports consulting for Abbvie, Altrubio, Allergan, Inc., Arena Pharmaceuticals, Aslan Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim Ltd., Bristol-Myers Squibb, Celgene Corp/Syneos, Connect BioPharma, GalenPharma/Atlantica, Genentech/Roche, Glycominds, InDex Pharmaceuticals, Ironwood Pharmaceuticals, Iterative Scopes, Janssen Pharmaceuticals, Lilly, Materia Prima, Pfizer, Prometheus Biosciences, Reistone, Takeda and Techlab, Inc.; and receiving grant support from Takeda., (© The Author(s), 2023.)

Loss of oral tolerance (LOT) to gluten, driven by dendritic cell (DC) priming of gluten-specific T helper 1 (Th1) cell immune responses, is a hallmark of celiac disease (CeD) and can be triggered by enteric viral infections. Whether certain commensals can moderate virus-mediated LOT remains elusive. Here, using a mouse model of virus-mediated LOT, we discovered that the gut-colonizing protist Tritrichomonas (T.) arnold promotes oral tolerance and protects against reovirus- and murine norovirus-mediated LOT, independent of the microbiota. Protection was not attributable to antiviral host responses or T. arnold-mediated innate type 2 immunity. Mechanistically, T. arnold directly restrained the proinflammatory program in dietary antigen-presenting DCs, subsequently limiting Th1 and promoting regulatory T cell responses. Finally, analysis of fecal microbiomes showed that T. arnold-related Parabasalid strains are underrepresented in human CeD patients. Altogether, these findings will motivate further exploration of oral-tolerance-promoting protists in CeD and other immune-mediated food sensitivities., Competing Interests: Declaration of interests E.F.V. is a member of the Biocodex International and National (Canada) Scientific Review Boards, a member of the Center for Gut Microbiome Research and Education Scientific Advisory Board of the AGA, Secretary of the International Society of the Study of Celiac Disease, and holds grants from Kallyope and Codexis, unrelated to this study. H.J.G. holds a grant from Codexis, unrelated to this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Children with autism spectrum disorder (ASD) face several challenges in the healthcare setting. This study defines the challenges experienced by children with autism in hospitals in Saudi Arabia. A cross-sectional study was conducted using a questionnaire for guardians of autistic children in outpatient clinics, autism support groups, and rehabilitation centers. A total of 199 participants were included. The medical procedures causing the most anxiety to children were injections and getting their blood drawn (68.3%), vital sign measurement (41.6%), and height and weight measurement (37.8%). Long waiting hours (44.1%), increased sensory stimuli (33.2%), and overcrowding of hospital staff (27.9%) were stress-inducing in the healthcare environment. The guardians recommended that loud noises (44.7%), crowdedness (41.2%), and long waiting hours (42.1%) be avoided. The nonverbal children experienced significantly higher levels ( p < 0.001) of agitation, irritability, and outbursts during doctor visits than their verbal counterparts. The children with intellectual disabilities were more tense and unresponsive during doctor visits (33.3%) than their intellectually able counterparts, who more frequently were calm and responsive (44.9%) during visits. Most patients with ASD face hardships during hospital visits. Nonverbal patients and those with intellectual disabilities have a higher tendency for hospital setting anxiety-induced outbursts, which may be eased by avoiding loud noise and overcrowding.

Autism spectrum disorder (ASD) prevalence has risen dramatically in recent decades; it is now common for children with ASD to seek dental care. Because their distinct behavioral patterns prevent them from receiving dental care in a traditional dental clinic, structured dental visual aids are required to help prepare them for their dental appointment. This study aimed to test the effect of "culturally adapted dental visual aids" in decreasing anxiety levels during dental visits in children with autism spectrum disorder (ASD). A randomized, controlled, blinded clinical trial was performed. Sixty-four children with ASD ages 6-12 years were assigned randomly into test and control groups based on the type of dental visual aids they received. The test group received "culturally adapted dental visual aids" created especially for the study, and the control group received "regular dental visual aids". Anxiety levels were assessed before and after using both dental visual aids. All data were processed using SPSS version 25.0. The test group had a significant decrease in anxiety levels compared to the control group ( p < 0.001). The "culturally adapted dental visual aids" have effectively reduced anxiety levels in children with ASD during dental visits.

Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia in patients with PSC. This inflammatory signature is characterized by antigen-driven interleukin-17A (IL-17A) + forkhead box P3 (FOXP3) + CD4 T cells that express a pathogenic IL-17 signature, as well as an expansion of IgG-secreting plasma cells. These results suggest that the mechanisms that drive the emergence of dysplasia in PSC and IBD are distinct and provide molecular insights that could guide prevention of colorectal cancer in individuals with PSC., (© 2023. The Author(s).)

Clonal hematopoiesis (CH) represents clonal expansion of mutated hematopoietic stem cells detectable in the peripheral blood or bone marrow through next generation sequencing. The current prevailing model posits that CH mutations detected in the peripheral blood mirror bone marrow mutations with clones widely disseminated across hematopoietic compartments. We sought to test the hypothesis that all clones are disseminated throughout hematopoietic tissues by comparing CH in hip vs peripheral blood specimens collected at the time of hip replacement surgery. Here, we show that patients with osteoarthritis have a high prevalence of CH, which involve genes encoding epigenetic modifiers and DNA damage repair pathway proteins. Importantly, we illustrate that CH, including clones with variant allele frequencies >10%, can be confined to specific bone marrow spaces and may be eliminated through surgical excision. Future work will define whether clones with somatic mutations in particular genes or clonal fractions of certain sizes are either more likely to be localized or are slower to disseminate into the peripheral blood and other bony sites., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge., Results: Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients., Conclusions: These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of "dysbiosis" that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease., (© 2023. The Author(s).)

Celiac disease (CeD) is an autoimmune disorder in which gluten-derived antigens trigger inflammation. Antigenic peptides must undergo site-specific deamidation to be presentable to CD4 + T cells in an HLA-DQ2 or -DQ8 restricted manner. While the biochemical basis for this post-translational modification is understood, its localization in the patient's intestine remains unknown. Here, we describe a mechanism by which gluten peptides undergo deamidation and concentration in the lysosomes of antigen-presenting cells, explaining how the concentration of gluten peptides necessary to elicit an inflammatory response in CeD patients is achieved. A ternary complex forms between a gluten peptide, transglutaminase-2 (TG2), and ubiquitous plasma protein α 2 -macroglobulin, and is endocytosed by LRP-1. The covalent TG2-peptide adduct undergoes endolysosomal decoupling, yielding the expected deamidated epitope. Our findings invoke a pathogenic role for dendritic cells and/or macrophages in CeD and implicate TG2 in the lysosomal clearance of unwanted self and foreign extracellular proteins., Competing Interests: Declaration of interests C.K. serves as a consultant to GSK and ImmunogenX. A patent application has been filed by Stanford University based on aspects of this work., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

There is growing recognition that regionalization of bacterial colonization and immunity along the intestinal tract has an important role in health and disease. Yet, the mechanisms underlying intestinal regionalization and its dysregulation in disease are not well understood. This study found that regional epithelial expression of the transcription factor GATA4 controls bacterial colonization and inflammatory tissue immunity in the proximal small intestine by regulating retinol metabolism and luminal IgA. Furthermore, in mice without jejunal GATA4 expression, the commensal segmented filamentous bacteria promoted pathogenic inflammatory immune responses that disrupted barrier function and increased mortality upon Citrobacter rodentium infection. In celiac disease patients, low GATA4 expression was associated with metabolic alterations, mucosal Actinobacillus, and increased IL-17 immunity. Taken together, these results reveal broad impacts of GATA4-regulated intestinal regionalization on bacterial colonization and tissue immunity, highlighting an elaborate interdependence of intestinal metabolism, immunity, and microbiota in homeostasis and disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Neuroepithelial crosstalk is critical for gut physiology. However, the mechanisms by which sensory neurons communicate with epithelial cells to mediate gut barrier protection at homeostasis and during inflammation are not well understood. Here, we find that Nav1.8 + CGRP + nociceptor neurons are juxtaposed with and signal to intestinal goblet cells to drive mucus secretion and gut protection. Nociceptor ablation led to decreased mucus thickness and dysbiosis, while chemogenetic nociceptor activation or capsaicin treatment induced mucus growth. Mouse and human goblet cells expressed Ramp1, receptor for the neuropeptide CGRP. Nociceptors signal via the CGRP-Ramp1 pathway to induce rapid goblet cell emptying and mucus secretion. Notably, commensal microbes activated nociceptors to control homeostatic CGRP release. In the absence of nociceptors or epithelial Ramp1, mice showed increased epithelial stress and susceptibility to colitis. Conversely, CGRP administration protected nociceptor-ablated mice against colitis. Our findings demonstrate a neuron-goblet cell axis that orchestrates gut mucosal barrier protection., Competing Interests: Declaration of interests A.J. is an employee of Genentech, Inc. I.M.C. serves on scientific advisory boards of GSK Pharmaceuticals and Limm Therapeutics. His lab receives research support from Moderna Inc. and AbbVie/Allergan Pharmaceuticals., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Celiac disease is an immune-mediated intestinal disorder that results from loss of oral tolerance (LOT) to dietary gluten. Reovirus elicits inflammatory Th1 cells and suppresses Treg responses to dietary antigen in a strain-dependent manner. Strain type 1 Lang (T1L) breaks oral tolerance, while strain type 3 Dearing reassortant virus (T3D-RV) does not. We discovered that intestinal infection by T1L in mice leads to the recruitment and activation of NK cells in mesenteric lymph nodes (MLNs) in a type I IFN-dependent manner. Once activated following infection, NK cells produce type II IFN and contribute to IFN-stimulated gene expression in the MLNs, which in turn induces inflammatory DC and T cell responses. Immune depletion of NK cells impairs T1L-induced LOT to newly introduced food antigen. These studies indicate that NK cells modulate the response to dietary antigen in the presence of a viral infection.

The triggers that drive interferon-γ (IFNγ)-producing CD8 T cell (Tc1 cell)-mediated autoimmune hepatitis (AIH) remain obscure. Here, we show that lack of hematopoietic Tet methylcytosine dioxygenase 2 (Tet2), an epigenetic regulator associated with autoimmunity, results in the development of microbiota-dependent AIH-like pathology, accompanied by hepatic enrichment of aryl hydrocarbon receptor (AhR) ligand-producing pathobionts and rampant Tc1 cell immunity. We report that AIH-like disease development is dependent on both IFNγ and AhR signaling, as blocking either reverts ongoing AIH-like pathology. Illustrating the critical role of AhR-ligand-producing pathobionts in this condition, hepatic translocation of the AhR ligand indole-3-aldehyde (I3A)-releasing Lactobacillus reuteri is sufficient to trigger AIH-like pathology. Finally, we demonstrate that I3A is required for L. reuteri-induced Tc1 cell differentiation in vitro and AIH-like pathology in vivo, both of which are restrained by Tet2 within CD8 T cells. This AIH-disease model may contribute to the development of therapeutics to alleviate AIH., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Intra-epithelial T cells make up a significant proportion of immune cells in the body, yet their development and function remain an enigma. In this issue of Immunity, Parsa et al. (2022) describe the differentiation and cross-protective function of CD4 + intra-epithelial T cells against enteric viruses., Competing Interests: Declaration of interests The authors have declared that no conflict of interest exists., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Autism spectrum disorder (ASD) prevalence has escalated in the last few decades; it is common to have children with ASD seek dental treatment. Their unique behavior patterns prevent them from attending a regular dental setting and receiving proper oral hygiene instructions (OHI); therefore, culturally adapted dental visual aids are necessary to teach them proper OHI. The aim of this study was to assess the effectiveness of culturally adapted dental visual aids in improving oral hygiene (OH) status in children with ASD. A blinded, randomized, controlled clinical trial with sixty-four children with ASD were randomly divided into two groups according to the type of dental visual aids given to them. The experimental group received culturally adapted dental visual aids developed specifically for the study, and the control group received regular dental visual aids. OH status was assessed before and after using the dental visual aids, and data were processed using SPSS version 25.0. OH status improved significantly in both groups after using the dental visual aids (p < 0.001, p < 0.001), respectively. The experimental group showed significant improvement in comparison to the control group in OH status (p = 0.030). Both dental visual aids showed effectiveness in improving OH status in children with ASD.

Celiac disease (CeD) is an autoimmune disorder induced by consuming gluten proteins from wheat, barley, and rye. Glutens resist gastrointestinal proteolysis, resulting in peptides that elicit inflammation in patients with CeD. Despite well-established connections between glutens and CeD, chemically defined, bioavailable peptides produced from dietary proteins have never been identified from humans in an unbiased manner. This is largely attributable to technical challenges, impeding our knowledge of potentially diverse peptide species that encounter the immune system. Here, we develop a liquid chromatographic-mass spectrometric workflow for untargeted sequence analysis of the urinary peptidome. We detect over 600 distinct dietary peptides, of which ~35% have a CeD-relevant T cell epitope and ~5% are known to stimulate innate immune responses. Remarkably, gluten peptides from patients with CeD qualitatively and quantitatively differ from controls. Our results provide a new foundation for understanding gluten immunogenicity, improving CeD management, and characterizing the dietary and urinary peptidomes., (© 2022. The Author(s).)

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders among children. Working memory deficits underlie many of the behavioural symptoms of ADHD. Alongside psychostimulant medications, strategies to improve working memory may play an important adjuvant role in the management of ADHD. In this study, we review the role of working memory deficits in ADHD, the evidence surrounding working memory training strategies in the management of the condition, and the factors affecting the success of these strategies in alleviating ADHD symptoms. More specifically, we review several non-pharmacological interventions that target working memory deficits in ADHD, with special emphasis on cognitive working memory training. We conclude that the development of evidence-based interventions such as computerised cognitive training (CCT) could provide an alternative or adjunct to the use of psychostimulants, especially in cases where side effects are a major issue., (Copyright © 2021 Al-Saad, Al-Jabri and Almarzouki.)

The unconventional T cell compartment encompasses a variety of cell subsets that straddle the line between innate and adaptive immunity, often reside at mucosal surfaces and can recognize a wide range of non-polymorphic ligands. Recent advances have highlighted the role of unconventional T cells in tissue homeostasis and disease. In this Review, we recast unconventional T cell subsets according to the class of ligand that they recognize; their expression of semi-invariant or diverse T cell receptors; the structural features that underlie ligand recognition; their acquisition of effector functions in the thymus or periphery; and their distinct functional properties. Unconventional T cells follow specific selection rules and are poised to recognize self or evolutionarily conserved microbial antigens. We discuss these features from an evolutionary perspective to provide insights into the development and function of unconventional T cells. Finally, we elaborate on the functional redundancy of unconventional T cells and their relationship to subsets of innate and adaptive lymphoid cells, and propose that the unconventional T cell compartment has a critical role in our survival by expanding and complementing the role of the conventional T cell compartment in protective immunity, tissue healing and barrier function., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Periodontal diseases are the result of an imbalance between the microbiota and immune defense. The role of yeast in the pathogenesis of these diseases has been studied. This study aims to assess the occurrence of Candida albicans in periodontitis., Materials and Methods: Fifty subjects were recruited for the study (15 healthy individuals and 35 periodontitis subjects). The periodontal examination and plaque sampling were carried out for all patients. Candida albicans identification was based on culture, direct examination, and polymerase chain reaction. The statistical analysis was performed by SPSS 20 (SPSS Inc., Chicago, IL, USA)., Results: Twenty percent of the diseased group harbored Candida albicans which was slightly higher than in the healthy group (7%), suggesting that, under normal conditions, yeast does not grow easily in subgingival sites. However, no significant difference between the healthy and periodontitis groups ( p =0.23) was found. Our results also indicated that the presence of Candida albicans was neither gender nor age related in the studied groups., Conclusion: The results of this study suggest that Candida albicans occurs in periodontitis. More studies are needed to clarify the potential role of this yeast in different stages and forms of the disease., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Brahim Jabri et al.)

Objectives: To describe the epidemiology, clinical and laboratory features, and outcome of children hospitalized with coronavirus disease 2019 (COVID-19) in the Middle East., Methods: A multicenter retrospective study of children hospitalized with COVID-19 in 7 centers across Oman between February and July 2020., Results: In total, 56 children <14 years old required hospitalization in 7 Omani centers over 5 months (February - July 2020). Thirty-seven (68%) children were admitted with uncomplicated COVID-19, 13 (23%) with pneumonia and 5 (9%) with multisystem inflammatory syndrome in children. Infants constituted 41% of cases (23/56), approximately half of whom (12/23, 52%) were <2-months old. Fever was the most common symptom (46, 82%), followed by respiratory symptoms (33, 59%), and gastrointestinal symptoms (31, 55%). Twenty-two (39%) children had underlying medical conditions: sickle cell disease (7, 13%), chronic respiratory disease (4, 7%) and severe neurological impairment (4, 7%). Leukocytosis, elevated inflammatory markers and anemia were independently associated with intensive care admission. There were no mortalities related to admission with COVID-19 in this cohort., Conclusion: Most of the children hospitalized with COVID-19 had a mild course and a satisfactory outcome. Sickle cell disease is the most common comorbidity associated with pediatric admission of COVID-19 in Oman., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Clonal hematopoiesis of indeterminate potential (CHIP) is predictive of hematological cancers and cardiovascular diseases, but the etiology of CHIP initiation and clonal expansion is unknown. Several lines of evidence suggest that proinflammatory cytokines may favor mutated hematopoietic stem cell expansion. To investigate the potential link between inflammation and CHIP, we performed targeted deep sequencing of 11 genes previously implicated in CHIP in 1887 subjects aged >70 years from the Montreal Heart Institute Biobank, of which 1359 had prior coronary artery disease (CAD), and 528 controls did not. We assessed association of CHIP with log transformed high-sensitivity C-reactive protein (hs-CRP), a validated biomarker of inflammation. CHIP was identified in 427 of the 1887 subjects (22.6%). CHIP mutations were more frequently identified in DNMT3A (11.6%) and TET2 (6.1%), with a higher proportion of TET2 mutations occurring in controls than in patients with CAD (9.0% vs 4.9%, P < .001). CHIP carriers had 21% higher hs-CRP levels compared with their noncarrier counterparts (eβ = 1.21, 95% confidence interval [CI]: 1.08 to 1.36; P = .001). A similar effect was observed in the subgroup of patients with known CAD (eβ = 1.22, 95% CI: 1.06 to 1.41; P = .005). These findings confirm the association between inflammation and CHIP. This association may open investigational avenues aimed at documenting mechanisms linking inflammation to clonal progression and ultimately supports prevention interventions to attenuate CHIP's impact on cardiovascular disease and cancer., (© 2020 by The American Society of Hematology.)

Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression.

Coeliac disease is a complex, polygenic inflammatory enteropathy caused by exposure to dietary gluten that occurs in a subset of genetically susceptible individuals who express either the HLA-DQ8 or HLA-DQ2 haplotypes 1,2 . The need to develop non-dietary treatments is now widely recognized 3 , but no pathophysiologically relevant gluten- and HLA-dependent preclinical model exists. Furthermore, although studies in humans have led to major advances in our understanding of the pathogenesis of coeliac disease 4 , the respective roles of disease-predisposing HLA molecules, and of adaptive and innate immunity in the development of tissue damage, have not been directly demonstrated. Here we describe a mouse model that reproduces the overexpression of interleukin-15 (IL-15) in the gut epithelium and lamina propria that is characteristic of active coeliac disease, expresses the predisposing HLA-DQ8 molecule, and develops villous atrophy after ingestion of gluten. Overexpression of IL-15 in both the epithelium and the lamina propria is required for the development of villous atrophy, which demonstrates the location-dependent central role of IL-15 in the pathogenesis of coeliac disease. In addition, CD4 + T cells and HLA-DQ8 have a crucial role in the licensing of cytotoxic T cells to mediate intestinal epithelial cell lysis. We also demonstrate a role for the cytokine interferon-γ (IFNγ) and the enzyme transglutaminase 2 (TG2) in tissue destruction. By reflecting the complex interaction between gluten, genetics and IL-15-driven tissue inflammation, this mouse model provides the opportunity to both increase our understanding of coeliac disease, and develop new therapeutic strategies.