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Histopathological image segmentation is a laborious and time-intensive task, often requiring analysis from experienced pathologists for accurate examinations. To reduce this burden, supervised machine-learning approaches have been adopted using large-scale annotated datasets for histopathological image analysis. However, in several scenarios, the availability of large-scale annotated data is a bottleneck while training such models. Self-supervised learning (SSL) is an alternative paradigm that provides some respite by constructing models utilizing only the unannotated data which is often abundant. The basic idea of SSL is to train a network to perform one or many pseudo or pretext tasks on unannotated data and use it subsequently as the basis for a variety of downstream tasks. It is seen that the success of SSL depends critically on the considered pretext task. While there have been many efforts in designing pretext tasks for classification problems, there have not been many attempts on SSL for histopathological image segmentation. Motivated by this, we propose an SSL approach for segmenting histopathological images via generative diffusion models. Our method is based on the observation that diffusion models effectively solve an image-to-image translation task akin to a segmentation task. Hence, we propose generative diffusion as the pretext task for histopathological image segmentation. We also utilize a multi-loss function-based fine-tuning for the downstream task. We validate our method using several metrics on two publicly available datasets along with a newly proposed head and neck (HN) cancer dataset containing Hematoxylin and Eosin (H&E) stained images along with annotations.

People with depression and other neuropsychiatric disorders can experience motivational dysfunctions such as fatigue and anergia, which involve reduced exertion of effort in goal-directed activity. To model effort-related motivational dysfunction, effort-based choice tasks can be used, in which rats can select between obtaining a preferred reinforcer by high exertion of effort vs. a low effort/less preferred option. Preclinical data indicate that dopamine transport (DAT) inhibitors can reverse pharmacologically-induced low-effort biases and increase selection of high-effort options in effort-based choice tasks. Although classical DAT blockers like cocaine can produce undesirable effects such as liability for misuse and psychotic reactions, not all DAT inhibitors have the same neurochemical profile. The current study characterized the effort-related effects of novel DAT inhibitors that are modafinil analogs and have a range of binding profiles and neurochemical actions (JJC8-088, JJC8-089, RDS3-094, and JJC8-091) by using two different effort-related choice behavior tasks in male Sprague-Dawley rats. JJC8-088, JJC8-089, and RDS3-094 significantly reversed the low-effort bias induced by the VMAT-2 inhibitor tetrabenazine, increasing selection of high-effort fixed ratio 5 lever pressing vs. chow intake. In addition, JJC8-089 reversed the effects of tetrabenazine in female rats. JJC8-088 and JJC8-089 also increased selection of high-effort progressive ratio responding in a choice task. However, JJC8-091 failed to produce these outcomes, potentially due to its unique pharmacological profile (i.e., binding to an occluded conformation of DAT). Assessment of a broad range of DAT inhibitors with different neurochemical characteristics may lead to the identification of compounds that are useful for treating motivational dysfunction in humans., (© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Cervical cancer (CC) is a key contributor to cancer-related mortality in several countries. The identification of molecular markers and the underlying mechanism may help improve CC management. We studied the regulation and biological function of the chromosome 14 microRNA cluster (C14MC; miR-379/miR-656) in CC. Most C14MC members exhibited considerably lower expression in CC tissues and cell lines in The Cancer Genome Atlas (TCGA) cervical squamous cell carcinoma and endocervical adenocarcinoma patient cohorts. Bisulfite Sanger sequencing revealed hypermethylation of the C14MC promoter in CC tissues and cell lines. 5-aza-2 deoxy cytidine treatment reactivated expression of the C14MC members. We demonstrated that C14MC is a methylation-regulated miRNA cluster via artificial methylation and luciferase reporter assays. C14MC downregulation correlated with poor overall survival and may promote metastasis. C14MC activation via the lentiviral-based CRISPRa approach inhibited growth, proliferation, migration, and invasion; enhanced G2/M arrest; and induced senescence. Post-transcriptional regulatory network analysis of C14MC transcriptomic data revealed enrichment of key cancer-related pathways, such as metabolism, the cell cycle, and phosphatidylinositol 3-kinase (PI3K)-AKT signaling. Reduced cell proliferation, growth, migration, invasion, and senescence correlated with the downregulation of active AKT, MYC, and cyclin E1 (CCNE1) and the overexpression of p16, p21, and p27. We showed that C14MC miRNA activation increases reactive oxygen species (ROS) levels, intracellular Ca 2+ levels, and lipid peroxidation rates, and inhibits epithelial-mesenchymal transition (EMT). C14MC targets pyruvate dehydrogenase kinase-3 (PDK3) according to the luciferase reporter assay. PDK3 is overexpressed in CC and is inversely correlated with C14MC. Both miR-494-mimic transfection and C14MC activation inhibited PDK3 expression. Reduced glucose uptake and lactate production, and upregulation of PDK3 upon C14MC activation suggest the potential role of these proteins in metabolic reprogramming. Finally, we showed that C14MC activation may inhibit EMT signaling. Thus, C14MC is a tumor-suppressive and methylation-regulated miRNA cluster in CC. Reactivation of C14MC can be useful in the management of CC., (© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Epigenetic alterations that lead to differential expression of microRNAs (miRNAs/miR) are known to regulate tumour cell states, epithelial-mesenchymal transition (EMT) and the progression to metastasis in breast cancer. This study explores the key contribution of miRNA-18a in mediating a hybrid E/M cell state that is pivotal to the malignant transformation and tumour progression in the aggressive ER-negative subtype of breast cancer. The expression status and associated effects of miR-18a were evaluated in patient-derived breast tumour samples in combination with gene expression data from public datasets, and further validated in in vitro and in vivo breast cancer model systems. The clinical relevance of the study findings was corroborated against human breast tumour specimens (n = 446 patients). The down-regulated expression of miR-18a observed in ER-negative tumours was found to drive the enrichment of hybrid epithelial/mesenchymal (E/M) cells with luminal attributes, enhanced traits of migration, stemness, drug-resistance and immunosuppression. Further analysis of the miR-18a targets highlighted possible hypoxia-inducible factor 1-alpha (HIF-1α)-mediated signalling in these tumours. This is a foremost report that validates the dual role of miR-18a in breast cancer that is subtype-specific based on hormone receptor expression. The study also features a novel association of low miR-18a levels and subsequent enrichment of hybrid E/M cells, increased migration and stemness in a subgroup of ER-negative tumours that may be attributed to HIF-1α mediated signalling. The results highlight the possibility of stratifying the ER-negative disease into clinically relevant groups by analysing miRNA signatures.

Abstract: Trichofolliculoma is a rare benign, hamartomatous adnexal tumour of the skin. Aetiology seems to be unclear. It is usually seen in adults, with no gender predilection. The most commonly involved sites are the face and scalp. It appears as a papule or nodule with small protruding hairs, which is a classic feature of the tumour. It has unique diagnostic and histopathological features that help in making a definitive diagnosis. Here, we report an exemplary case of an adult male patient aged 45 years with a gradual progressive diffuse swelling on the left side of the face for 1.5 years. Clinically, it was diagnosed as a sebaceous cyst, but after the biopsy histopathological evaluation was performed, and the diagnosis was confirmed as trichofolliculoma., (Copyright © 2024 Copyright: © 2024 Indian Journal of Dental Research.)

Objectives: The objectives of this study are to explore and evaluate the automation of anatomical landmark localization in cephalometric images using machine learning techniques, with a focus on feature extraction and combinations, contextual analysis, and model interpretability through Shapley Additive exPlanations (SHAP) values., Methods: We conducted extensive experimentation on a private dataset of 300 lateral cephalograms to thoroughly study the annotation results obtained using pixel feature descriptors including raw pixel, gradient magnitude, gradient direction, and histogram-oriented gradient (HOG) values. The study includes evaluation and comparison of these feature descriptions calculated at different contexts namely local, pyramid, and global. The feature descriptor obtained using individual combinations is used to discern between landmark and nonlandmark pixels using classification method. Additionally, this study addresses the opacity of LGBM ensemble tree models across landmarks, introducing SHAP values to enhance interpretability., Results: The performance of feature combinations was assessed using metrics like mean radial error, standard deviation, success detection rate (SDR) (2 mm), and test time. Remarkably, among all the combinations explored, both the HOG and gradient direction operations demonstrated significant performance across all context combinations. At the contextual level, the global texture outperformed the others, although it came with the trade-off of increased test time. The HOG in the local context emerged as the top performer with an SDR of 75.84% compared to others., Conclusions: The presented analysis enhances the understanding of the significance of different features and their combinations in the realm of landmark annotation but also paves the way for further exploration of landmark-specific feature combination methods, facilitated by explainability., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Institute of Radiology and the International Association of Dentomaxillofacial Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Alzheimer's disease (AD) is a multifactorial disorder resulting from the complex interaction between genetic, epigenetic, and environmental factors. It represents an impending epidemic and lacks effective pharmacological interventions. The emergence of high throughput sequencing techniques and comprehensive genome evaluation has uncovered a diverse spectrum of noncoding RNA (ncRNA) families. ncRNAs are the critical modulators of an eclectic array of biological processes and are now transpiring as imperative players in diagnosing and treating various diseases, including neurodegenerative disorders. Several ncRNAs are explicitly augmented in the brain, wherein they potentially regulate cognitive abilities and other functions of the central nervous system. Growing evidence suggests the substantial role of ncRNAs as modulators of tau phosphorylation, Aβ production, neuroinflammation, and neuronal survival. It indicates their therapeutic relevance as a biomarker and druggable targets against AD. The current review summarizes the existing literature on the functional significance of ncRNAs in AD pathogenesis and its imminent implications in clinics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Infections by multidrug resistant bacteria (MDR) are becoming increasingly difficult to treat and alternative approaches like phage therapy, which is unhindered by drug resistance, are urgently needed to tackle MDR bacterial infections. During phage therapy phage cocktails targeting different receptors are likely to be more effective than monophages. In the present study, phages targeting carbapenem resistant clinical isolate of E. coli U1007 was isolated from Ganges River (U1G), Cooum River (CR) and Hospital waste water (M). Capsid architecture discerned using TEM identified the phage families as Podoviridae for U1G, Myoviridae for CR and Siphoviridae for M phage. Genome sequencing showed the phage genomes varied in size U1G (73,275 bp) CR (45,236 bp) and M (45,294 bp). All three genomes lacked genes encoding tRNA sequence, antibiotic resistant or virulent genes. A machine learning (ML) based multi-class classification model using Random Forest, Logistic Regression, and Decision Tree were employed to predict the host receptor targeted by receptor binding protein of all 3 phages and the best performing algorithm Random Forest predicted LPS O antigen, LamB or OmpC for U1G; FhuA, OmpC for CR phage; and FhuA, LamB, TonB or OmpF for the M phage. OmpC was validated as receptor for U1G by physiological experiments. In vivo intramuscular infection study in zebrafish showed that cocktail of dual phages (U1G + M) along with colsitin resulted in a significant 3.5 log decline in cell counts. Our study highlights the potential of ML tool to predict host receptor and proves the utility of phage cocktail to restrict E. coli U1007 in vivo., (© 2023. The Author(s).)

Introduction: Two-dimensional cephalometric image analysis plays a crucial role in orthodontic diagnosis and treatment planning. While deep learning-based algorithms have emerged to automate the laborious task of anatomical landmark annotation, their effectiveness is hampered by the challenges of acquiring and labelling clinical data. In this study, we propose a model that leverages conventional machine learning techniques to enhance the accuracy of landmark detection using limited dataset., Materials and Methods: Our methodology involves coarse localization through region of interest (ROI) extraction and fine localization utilizing histogram-oriented gradient (HOG) feature. The image patch containing landmark pixels is classified using the light gradient boosting machine (LGBM) algorithm. To evaluate our model's performance, we conducted rigorous tests on the ISBI Cephalometric dataset and Dental Cepha dataset, aiming to achieve accuracy within a 2 mm radial precision range. We also employed cross-validation to assess our approach, providing a robust evaluation., Results: Our model's performance on the ISBI Cephalometric dataset showed an accuracy rate of 77.11% within the desired 2 mm radial precision range. The cross-validation results further confirmed the effectiveness of our approach, yielding a mean accuracy of 78.17%. Additionally, we applied our model to the Dental Cepha dataset, where we achieved a remarkable landmark detection accuracy of 84%., Conclusion: The results demonstrate that traditional machine learning techniques can be effective for accurate landmark detection in cephalometric images, even with limited data. Our findings highlight the potential of these techniques for clinical applications, where large datasets of labelled images may not be available., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© The Association of Oral and Maxillofacial Surgeons of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Early motor and sensory developmental delays precede Autism Spectrum Disorder (ASD) diagnosis and may serve as early indicators of ASD. The literature on sensorimotor development in animal models is sparse, male centered, and has mixed findings. We characterized early development in a prenatal valproic acid (VPA) model of ASD and found sex-specific developmental delays in VPA rats. We created a developmental composite score combining 15 test readouts, yielding a reliable gestalt measure spanning physical, sensory, and motor development, that effectively discriminated between VPA and control groups. Considering the heterogeneity in ASD phenotype, the developmental composite offers a robust metric that can enable comparison across different animal models of ASD and can serve as an outcome measure for early intervention studies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Diabetes is a prevalent and debilitating metabolic disorder affecting a large population worldwide. The condition is characterized by insulin resistance and impaired function of pancreatic β-cells, leading to elevated blood glucose levels. In this study, the antidiabetic effects of Erigeron annuus extract (EAE) on zebrafish with damaged pancreatic islets caused by insulin resistance were investigated. The study utilized the zebrafish model to monitor live pancreatic islets. RNA sequencing was also conducted to determine the mechanism by which EAE exerts its antidiabetic effect. The results showed that EAE was effective in recovering reduced islets in excess insulin-induced zebrafish. The effective concentration at 50% (EC 50 ) of EAE was determined to be 0.54 μg/mL, while the lethal concentration at 50% (LC 50 ) was calculated as 202.5 μg/mL. RNA sequencing indicated that the mode of action of EAE is related to its ability to induce mitochondrial damage and suppress endoplasmic reticulum stress. The findings of this study demonstrate the efficacy and therapeutic potential of EAE in treating insulin resistance in zebrafish. The results suggest that EAE may offer a promising approach for the management of diabetes by reducing mitochondrial damage and suppressing endoplasmic reticulum stress. Further research is required to establish the clinical application of EAE in diabetic patients.

A private-academic partnership built the Vaccine Equity Planner (VEP) to help decision-makers improve geographic access to COVID-19 vaccinations across the United States by identifying vaccine deserts and facilities that could fill those deserts. The VEP presented complex, updated data in an intuitive form during a rapidly changing pandemic situation. The persistence of vaccine deserts in every state as COVID-19 booster recommendations develop suggests that vaccine delivery can be improved. Underresourced public health systems benefit from tools providing real-time, accurate, actionable data. ( Am J Public Health . 2023;113(4):363-367. https://doi.org/10.2105/AJPH.2022.307198).

Breast cancer (BC) among premenopausal women is an aggressive disease associated with poor outcome despite intensive treatment. Higher burden is observed in southeast Asian countries attributed to younger population structure. We compared the reproductive and clinicopathological characteristics, distribution of subtypes and survival between pre and postmenopausal women from a retrospective cohort of BC patients with median follow up over 6 years to examine the differences. In our cohort of 446 BC patients, 162/446 (36.3%) were premenopausal. Parity and age at last childbirth were significantly different between pre and postmenopausal women. Premenopausal BC had a higher proportion of HER2 amplified and triple negative breast cancer (TNBC) tumors (p = 0.012). Stratified analysis by molecular subtypes showed TNBC had significantly better disease free (DFS) and overall survival (OS) among premenopausal group (mean survival, pre vs. post, DFS = 79.2 vs. 54.0 months, OS = 72.5 vs. 49.5 months, p = 0.002 for both). Analysis on external datasets (SCAN-B, METABRIC) confirmed this finding for overall survival. Our data confirmed the previously observed association of clinical and pathological features between pre and postmenopausal BC. Exploration of better survival among premenopausal TNBC tumors is warranted in larger cohorts with long term follow up., (© 2023. The Author(s).)

Stem cell factor (SCF) is a cytokine that regulates hematopoiesis and other biological processes. While clinical treatments using SCF would be highly beneficial, these have been limited by toxicity related to mast cell activation. Transmembrane SCF (tmSCF) has differential activity from soluble SCF and has not been explored as a therapeutic agent. We created novel therapeutics using tmSCF embedded in proteoliposomes or lipid nanodiscs. Mouse models of anaphylaxis and ischemia revealed the tmSCF-based therapies did not activate mast cells and improved the revascularization in the ischemic hind limb. Proteoliposomal tmSCF preferentially acted on endothelial cells to induce angiogenesis while tmSCF nanodiscs had greater activity in inducing stem cell mobilization and recruitment to the site of injury. The type of lipid nanocarrier used altered the relative cellular uptake pathways and signaling in a cell type dependent manner. Overall, we found that tmSCF-based therapies can provide therapeutic benefits without off target effects., (© 2022. The Author(s).)

Instrumental behavior is a very complex and multifaceted process. Behavioral output during instrumental performance is influenced by a variety of factors, including associative conditioning, directional and activational aspects of motivation, affect, action selection and execution, and decision-making functions. Detailed assessments of instrumental behavior can focus on the temporal characteristics of instrumental behavior such as local frequency and response duration, and biophysical measures of response topography such as force output over time. Furthermore, engaging in motivated behavior can require exertion of effort and effort-based decision making. The present review provides an overview of research on the specific deficits in operant behavior induced by dopamine antagonism and depletion. Furthermore, it discusses research on effort-based decision making, and highlights the complexities and seeming paradoxes that are revealed when detailed analyses of operant behavior are conducted, and instrumental behavior is put in the context of factors such as primary or unconditioned food reinforcement, appetite, binge-like eating, and response choice. Although impairments in mesolimbic dopamine are sometimes labeled as being due to "anhedonia", a detailed deconstruction of the findings in this area of research point to a much more complex and nuanced picture of the role that dopamine plays in regulating instrumental behavior. Low doses of DA antagonists and accumbens dopamine depletions blunt the exertion of physical effort as measured by several different challenges in animal studies (e.g., lever pressing, barrier climbing, wheel running), and yet leave fundamental aspects of hedonic reactivity, food motivation, and reinforcement intact. Continued research on the specific features of instrumental behaviors that regulate the sensitivity to impaired dopamine transmission across a number of contexts is important for resolving some of the complexities that are evident in this area of inquiry. These investigations can also provide insights into psychomotor and motivational dysfunctions that are seen in neuropsychiatric conditions such as depression, schizophrenia, and Parkinson's disease., (Copyright © 2022. Published by Elsevier Inc.)

The development of COVID-19 vaccines was promptly regulated to ensure the best possible approach. By January 2022, 75 candidates reached preclinical evaluation in various animal models, 114 vaccines were in clinical trials on humans, and 48 were in the final testing stages. Vaccine platforms range from whole virus vaccines to nucleic acid vaccines, which are the most promising in prompt availability and safety. The USA and Europe have approved vaccines developed by Pfizer-BioNTech (BNT162b2) and Moderna (mRNa1273). So far, Pfizer-BioNTech, Moderna, Johnson & Johnson, AstraZeneca-University of Oxford, Sinopharm, Sinovac Biotech Gamaleya, Bharat Biotech, and Novavax have documented effective vaccines. Even with technological advances and a fast-paced development approach, many limitations and problems need to be overcome before a large-scale production of new vaccines can start. The Key is to ensure equal and fair distribution globally through regulatory measures. Recent studies link Bacillus Calmette-Guérin (BCG) vaccination programs and lower disease severity., (Copyright © 2022. Published by Elsevier Inc.)

Aim and Objective: To evaluate whether silver diamine fluoride (SDF) is effective in the management of dental caries., Background: Dental caries is most common chronic disease and conventional treatment method could not tackle the problem completely. The use of silver compounds in dentistry is over a 100 years. Silver diamine fluoride has become a newer trend in handling the caries especially in young and apprehensive children. It is a noninvasive method of arresting caries which is painless, safe, and cost effective. This article describes the trends in silver diamine fluoride in arresting caries. The combined effects of remineralizing and antibacterial property make SDF an effective cariostatic agent., Review Results: Articles were searched in electronic data bases for literature. In vivo studies, in vitro studies, systematic reviews and case reports were included., Conclusion: Silver diamine fluoride is effective in the management of caries in primary dentition. There is a little effect of silver diamine fluoride in permanent molars., Clinical Importance: In the current scenario of raising importance of minimal invasive dentistry and preventive dentistry, silver diamine fluoride is an efficient tool in the management of caries., How to Cite This Article: Surendranath P, Krishnappa S, Srinath S. Silver Diamine Fluoride in Preventing Caries: A Review of Current Trends. Int J Clin Pediatr Dent 2022;15(S-2):S247-S251., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2022; The Author(s).)

Background: Coronavirus disease-2019 COVID-19) pandemic has been sweeping around the globe and the cases have been reported in India since the second week of March, with Chennai being one of the most affected cities. Healthcare professionals, particularly the dental personnel have a higher risk of infection due to close face-to-face contact and the risk of inhalation of aerosolised particles., Aim: The aim of this study was to assess the knowledge, attitude and practice about COVID-19 among interns, post-graduate trainees and dental practitioners., Material and Methods: A cross-sectional survey was conducted using Google forms among three groups: interns, post-graduate trainees and dental practitioners. Data obtained was analysed by Chi-square test, Kruskal-Wallis and post hoc test using SPSS IBM software., Results: Of total score of 9 for knowledge-based questions, the score obtained by interns, post-graduate trainees and practitioners were 7.2, 7.2 and 7.5, respectively, with no statistically significant difference among the groups (P = 0.24). Of total score of 4 for attitude-based questions, the score obtained by interns, post-graduate trainees and practitioners were 1.6, 2.0, and 1.9, respectively, with statistically significant difference among the groups (0.009). Of total score of 7 for practice-based questions, the score obtained by interns, post-graduate trainees and practitioners were 3.2, 3.3, and 3.1, respectively, with no statistically significant difference among them (P = 0.63)., Conclusion: Though the knowledge about COVID-19 appeared adequate, the attitude and practice component needs improvement. Continuing dental education programs and webinars can be conducted to update the dental professionals about the protocols to be followed during COVID-19 pandemic., Competing Interests: None

A 53-year-old man presented acutely to the Accident and Emergency department with a 2-day history of progressive odynophagia and shortness of breath. The patient had stridor at rest and acute epiglottitis was suspected. The patient was transferred urgently to theatre for intubation but due to a severely oedematous airway, this was unsuccessful and emergency tracheotomy was performed by the ENT team. Throughout admission the only positive microbiological sample was a nasopharyngeal swab for SARS-CoV-2 infection. In the absence of other positive microbiology, it is highly likely that COVID-19 was the aetiological cause of acute epiglottitis in this instance., Learning Points: COVID-19 infection is a novel disease with multiple presentations; it should be considered as a possible causative organism in patients presenting with acute epiglottitis.Due to the time delay in taking samples for microbiology and results being available, treatment should be commenced with antibiotics, nebulised adrenaline and steroids to cover bacterial infection.Presentation can occur following a delayed inflammatory response and treatment should target the organ system involved., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2021.)

Purpose: The need to enhance mental health in primary care settings for infants and toddlers is increasingly becoming apparent. However, the lack of trained healthcare personnel and culturally appropriate measures makes it a challenge in low- and middle-income countries. A needs-based assessment of the extent of the problems in toddlers will help address the lacunae in providing mental health services., Methods: A needs-based assessment was carried out of a community sample of 9,287 mothers with toddlers aged between 13 and 25 months in Kerala, India. This assessment was conducted by junior public health nurses using an indigenously developed checklist titled 'Screening checklist for Behavioural, Emotional and Rhythm-related disturbances in Toddlers' (S-BERT)., Results: According to the mothers surveyed, 30.4% of toddlers had concerning or distress causing behaviours. Three factors, namely behavioural, rhythm-related and emotional disturbances, were deemed significant when the item response theory was used to examine the factor structure of S-BERT., Conclusion: This study suggests that behaviours that cause distress to mothers of toddlers are common, if queried specifically. Given the constraints in health resources as the cultural factors in operation, use of indigenous tools and principles of collaborative stepped care may be the way forward., (© 2021 Michigan Association for Infant Mental Health.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory tract virus that causes Coronavirus disease (COVID-19). The virus originated in Wuhan, China, in December 2019 and has spread across the globe to-date. The disease ranges from asymptomatic carriers to symptoms such as fever, sore throat, cough, lung infections, and in severe cases, acute respiratory distress syndrome, sepsis, and death. As many as 50% of patients reported having at least one comorbidities with COVID-19 upon hospital admission. Hypertension, diabetes, chronic obstructive pulmonary disease, obesity, and cardiovascular diseases are among the most commonly reported. Comorbidities are contributing to acute disease prognosis and increased risk of severe symptoms. Around 70% of patients who require ICU care have been observed to have comorbidities. This review intends to understand how some of these comorbidities affect the disease's prognosis and how severe the outcome can be expected., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To study the prevalence and correlates of self-reported ADHD symptoms among school-going adolescents from Kerala, India. Method: Seven thousand five hundred sixty students from Classes 8, 10, and 12, aged 12 to 19 years, across 73 schools selected by cluster random sampling, were invited to participate, but only 7,150 successfully completed the questionnaire incorporating standardized instruments. Results: Three hundred five (4.3%) self-reported symptoms for ADHD combined type, 131 (1.8%) for ADHD hyperactive-impulsive type, and 102 (1.4%) for ADHD inattentive type with a male predominance. Binary logistic regression analysis showed that those with symptoms of ADHD (combined type) compared with the non-ADHD group had poorer academic performance, significantly higher substance use, psychological distress, suicidality, and sexual abuse. Conclusion: The high prevalence of self-reported ADHD symptoms and its association with negative correlates previously reported in literature in those with a diagnosis of ADHD suggests that clinically significant self-reported ADHD symptoms could be as disabling as ADHD.

Despite the established benefits of long-term endocrine therapy, women with hormone receptor-positive breast cancer remain at risk for late relapse. The basis of this is multi-factorial including genetic, epigenetic, and host factors. In this study we have explored the epigenetic regulation of estrogen receptor (ER)-dependent molecular and cellular phenotype by hsa-miR-18a-5p using well-established human ER-positive (ER+) breast cancer cell lines. miR-18a was overexpressed in MCF7 and ZR-75-1 and this led to an increase in the proliferative ability of the cells and concurrently resulted in decreased expression of luminal markers and higher expression of the basal marker, cytokeratin 14. The cells became more migratory with a significant repression of E-cadherin and activation of the Wnt noncanonical pathway. We observed an activation of the planar cell polarity (PCP) pathway with increased activation of JNK pathway and eventually change in actin dynamics. There was increased F-actin polymerization in cells with higher expression of miR-18a. Examination of miR-18a expression in a set of human ER+ breast cancer specimens showed a negative correlation between miR-18a and ESR1 transcripts as well as ER protein. Kaplan-Meier survival analysis of the cohort stratified by tumor hsa-miR-18a-5p levels produced significant differences in disease-free survival (log rank P < .05). This observation was independently validated in the METABRIC cohort. These data provide support for a role of hsa-miR-18a-5p in altering the proliferative and migratory behavior of ER+ cells and its potential utility as a prognostic marker in clinical ER+ breast cancers., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Different amounts of graphene-wrapped magnesium oxide (G@MgO) powders are uniformly dispersed in poly(vinyl alcohol) (PVA) solution in different experiments to obtain solutions which are coagulated to obtain solid materials, which are then hot pressed at 413 K and 3 t of pressure to finally obtain 1 mm thick freestanding G@MgO/PVA composite sheets in which the constituents, namely, graphene and MgO (in the form of G@MgO), are the nanofillers in PVA matrix. During synthesis of G@MgO powder, MgO nanoparticles are in situ wrapped by the graphene nanosheets as revealed by electron microscopy. Uniformity of G@MgO dispersion in PVA was confirmed by secondary electron micrographs and the consistency in X-ray diffraction and Raman scattering data collected from different locations of the samples. Temperature (303-393 K) dependent complex permittivity of G@MgO/PVA composite sheets (including those prepared by casting) in low frequency (20 Hz to 2 MHz) and high frequency (i.e., X-band, 8.2-12.4 GHz) ranges are measured. In both frequency ranges, G@MgO/PVA composite sheets prepared by coagulation exhibited dielectric properties superior to those of PVA and G@MgO/PVA composite sheets prepared by casting. A strong interfacial polarization is observed in coagulated and as-cast G@MgO/PVA composite sheets. It is noticed from the calculated activation energies that conduction is the dominating mechanism for energy transfer in both composite sheets' cases, while it is predominating in coagulated composite sheets due to the better network formation of the fillers in the coagulated samples than in the cast composite samples. The electromagnetic interference shielding effectiveness (EMI SE) values in the X-band frequency range (i.e., 8.2-12.4 GHz) of the G@MgO/PVA composite sheets prepared by coagulation are more than those prepared by casting for a particular weight fraction of G@MgO. At 393 K, for a particular G@MgO/PVA composite sheet prepared by coagulation, an excellent EMI SE of ∼27.5 dB is measured. It is also experimentally elucidated that the absorption is the dominating mechanism for EMI SE in the prepared composite sheets.

Till date researchers have elucidated the neurobiological substrates in OCD using methods like neuroimaging. However, a potential biomarker is still elusive. The present study is an attempt to identify a potential biomarker in pediatric OCD using eye tracking. The present study measured pro-saccade and anti-saccade parameters in 36 cases of pediatric OCD and 31 healthy controls. There was no significant difference between cases and controls in the error rate, peak velocity, position gain and latency measures in both pro-saccade and anti-saccade eye tracking tasks. With age, anti-saccades become slower in velocity, faster in response and more accurate irrespective of disorder status of the child. Pro-saccades also show a similar effect that is less prominent than anti-saccades. Gain measures more significantly vary with age in children with OCD than the controls, whereas latency measures positively correlated with age in children with OCD as opposed to being negatively correlated in the controls. Findings of this study do not support any of the eye tracking measures as putative diagnostic bio-markers in OCD. However, latency and gain parameters across different age groups in anti-saccade tasks need to be explored in future studies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Anxiety spectrum disorders are the most prevalent psychopathology among children and adolescents. Qualitative research in childhood anxiety disorders can provide valuable insights regarding interventions. The objectives of this study were to examine the child's perspectives on the subjective experience of concerns, the impact of the symptoms on socioacademic functioning, and the process of recovery with interventions., Methods: Children and adolescents aged 6-16 years, presenting with any subtype of anxiety spectrum disorder as per International Classification of Diseases and Related Health problems, 10 th Revision (ICD-10) Diagnostic Criteria for Research, were included. Convenience sampling was used, and 30 children fulfilling inclusion and exclusion criteria were selected. An interview guide with simple questions to facilitate response was used, at the baseline and 12 th week of follow-up, to generate a written narrative account of the experience of concerns, the impact of symptoms, and the treatment process. Children received treatment as usual, which included a workbook-based cognitive behavioral intervention., Results: Content analysis was done using 30 baseline and 20 follow-up narratives. Clustering of themes were done. Themes related to the recovery process reflected perceived improvement in academic performance and competence, apart from the improvement in symptoms. There were more themes in favor of cognitive interventions., Conclusion: Children's narratives highlight the importance of cognitive interventions for anxiety disorders., Competing Interests: There are no conflicts of interest.

Background: Although anxiety disorders are the most prevalent psychiatric disorders among children and adolescents, there is a paucity of research on the course and outcome of anxiety spectrum disorders in low and middle-income countries., Methods: 60 children and adolescents aged 6-16 years with anxiety spectrum disorders attending the child and adolescent psychiatry department in a tertiary care center from India were included after taking written informed consent and assent in this prospective study conducted between April 2012 to May 2014. Assessments were done at baseline, 12 weeks and 24 weeks using pediatric anxiety rating scale, clinical global impression-severity, clinical global assessment scale and pediatric quality of life scale; MINI-KID (version 6.0) was used to examine remission status., Results: Mean age of children was 12.68 years and mean duration of illness was 34.52 months. Follow-up rate at 24 weeks was 80% with a remission rate of 64.6%. Socio-demographic factors did not affect the baseline severity or course and outcome measures. Children with greater baseline severity and social phobia had a less favorable outcome at 24 weeks. Improvements made in the initial 12 weeks were maintained at 24 weeks follow up. These findings are in line with earlier studies from high-income countries., Limitations: Small sample size, attrition, rater bias., Conclusion: The study has shown a favorable outcome in children and adolescents with anxiety spectrum disorders receiving treatment-as-usual in a tertiary care setting. Adolescents who present with greater severity, comorbid with other anxiety disorders and depression at baseline require intensive intervention, and long-term follow up. There is a need for interventional research with specific focus on universal preventive programs for anxiety spectrum disorders that are feasible for delivery in low and middle-income countries.

Competing Interests: There are no conflicts of interest.

Context: Almost 1/5 th of the adolescent population suffers from mental morbidity. In older adolescents, clinical challenges are accompanied by unique psychosocial and developmental needs. Recent legislations in India - the Mental Health Care Act, 2017 and the Juvenile Justice Act, 2015 - mandate specific arrangements and provisions for evaluation and treatment of children and adolescents. A separate inpatient Adolescent Psychiatry Center (APC) was started at National Institute of Mental Health and Neurosciences, Bangalore, in 2016., Aims: (a) The aim of this study is to present the need for, development, infrastructure and workforce at APC; (b) to describe clinical profile of adolescents admitted to APC and (c) to identify clinical and psychosocial challenges in the management of older adolescents., Setting and Design: The paper covers consecutive inpatient admissions over the first 7 months of APC., Materials and Methods: Data were gathered from a review of hospital records, staff meetings, and case files., Statistical Analysis: Qualitative data, such as clinical management challenges, are summarized under major emergent themes. Quantitative data are summarized as means with standard deviations and frequencies with percentages., Results: Males, from urban, nuclear family background constituted the majority admissions. Family stressors and risk behaviors were prevalent. Unique clinical challenges included - risk behaviors, issues related to autonomy, conflict with family and conflict with the legal system., Conclusions: Older adolescents need to be treated in an environment appropriate to their age and developmental stage. Restructuring of spaces, routines, and creative inputs to interventions strategies must be made for healing environments for youngsters. APC could be a model for the development of other similar centers., Competing Interests: There are no conflicts of interest

Objective: To examine the differences in whole brain topology and connectivity in 17 children of the ages 3-8 years across severity of ASD, we performed resting state fMRI using a 3T MRI scanner and graph theoretical analysis of networks., Method: Patients were partitioned into two cohorts based on the severity of ASD, determined using the Childhood Autism Rating Scale (CARS) scores (Mild, 30-36; Severe, 37+). Standard preprocessing pipeline was used, followed by independent component analysis (ICA) to identify regions of interest (ROIs) to construct subject-specific Z-correlation matrices representing the whole brain network. Following which, graph theory measures were calculated in the range of sparsity 6%-35% and statistically analyzed, and corrected for significance (FDR corrected, p < 0.05). Regional clustering coefficient that revealed significant between-group (mild vs. severe) differences were correlated against clinical scores (CARS)., Results: Children with severe ASD revealed significantly increased clustering coefficient and small-worldness compared to those with mild or moderate ASD. Region of interest analysis revealed altered clustering in the Heschl's gyrus that significantly correlated with CARS scores., Conclusion: The findings from the current study provide early stage evidence of aberrant brain connectivity appearing in severe ASD, prior to the effect of environmental bias and pruning mechanisms. The clustering of the Heschl's gyrus correlated to the severity of ASD symptoms and agrees with current literature on ASD-associated cortical changes, reflecting early changes to language processing regions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Multiple studies have identified the presence of peripheral immune aberrations in subjects with Autism Spectrum Disorder (ASD). However, comprehensive assessment of these peripheral immune aberrations, in the cellular and systemic compartments, in a single group of subjects with ASD is lacking. We assessed proportions of various subsets of immune cells in peripheral blood (T helper cells, T regulatory cells, B cells, monocytes, Natural Killer cells, dendritic cells) by multi-parametric flow cytometry in 50 children with ASD and compared it with thirty healthy controls matched for age, gender, socio-economic status and body mass index. There were no significant differences noted in the proportion of T regulatory cells, B cells, monocytes and Natural Killer cells, between ASD subjects and controls. On the contrary, the proportion of activated Th17 and myeloid dendritic cells were significantly higher in children with ASD. Based on these findings, group comparison of serum levels of Th17 cytokines (interleukin-6, interleukin-17A) was performed. Elevated serum levels of interleukin-6 and interleukin-17A in children with ASD corroborated our immunophenotyping findings. We did not find any significant differences among the pro-inflammatory (interleukin-1β), Th1 (interferon-γ) and Th2 (interleukin-4) cytokines. This is the first evidence with concurrent findings from immunophenotyping and cytokine data demonstrating activation of the Th17 pathway in subjects with ASD. This finding assumes significance in the light of recent maternal immune activation mouse model study that has highlighted the role of Th17 pathway in the pathophysiology of ASD. Future longitudinal studies are needed to clarify the role of this dysregulated immune pathway in the development of ASD., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

On the basis of (i) particle image velocimetry data of a turbulent boundary layer with large field of view and good spatial resolution and (ii) a mathematical relation between the energy spectrum and specifically modeled flow structures, we show that the scalings of the streamwise energy spectrum E&#95;{11}(k&#95;{x}) in a wave-number range directly affected by the wall are determined by wall-attached eddies but are not given by the Townsend-Perry attached eddy model's prediction of these spectra, at least at the Reynolds numbers Re&#95;{τ} considered here which are between 10^{3} and 10^{4}. Instead, we find E&#95;{11}(k&#95;{x})∼k&#95;{x}^{-1-p} where p varies smoothly with distance to the wall from negative values in the buffer layer to positive values in the inertial layer. The exponent p characterizes the turbulence levels inside wall-attached streaky structures conditional on the length of these structures. A particular consequence is that the skin friction velocity is not sufficient to scale E&#95;{11}(k&#95;{x}) for wave numbers directly affected by the wall.

Background: Stroke, characterized by sudden loss of cerebral function, is among one of the leading cause of death and disability world over. The newer treatment modalities have changed the landscape of stroke treatment but are very much time bound., Aim: To characterize pre-hospital and in-hospital factors affecting acute stroke management thus defining lacunae in stroke management., Subjects and Methods: A prospective observational study, conducted at the emergency department of a tertiary care center in southern India from August 2015 to July 2016. All stroke patients presenting within first 24 hours of onset were included. A pre -defined Knowledge-Attitude-Practice (KAP) questionnaire was used., Results: Total of 133 patients were eligible out of which 28 were excluded for various reasons. Majority were >60 years age and male (61%). About 60% arrived within window. Distance from the hospital was one of the major factors for arrival within the window period. When compared by KAP questionnaire, bystanders of those arriving within window period had better awareness of stroke symptoms., Conclusions: Improving awareness of stroke symptoms and increasing availability of EMS is likely increase chances of stroke patients receiving appropriate acute management., Competing Interests: There are no conflicts of interest.

Malic acid (MA), one of the major organic acid exudates from roots, plays a significant role in the chemotaxis of beneficial bacteria to the plant's rhizosphere. In this study, the effect of a plant-growth-promoting rhizobacterium, Bacillus subtilis RR4, on the synthesis and exudation of MA from roots is demonstrated in rice. To test the chemotactic ability of strain RR4 towards MA, a capillary chemotaxis assay was performed, which revealed a positive response (relative chemotactic ratio of 6.15 with 10 μmol/L MA); with increasing concentrations of MA, an elevated chemotactic response was observed. Quantitative polymerase chain reaction, performed to analyze the influence of RR4 on the MA biosynthetic gene, malate synthase (OsMS), and the transporter gene, aluminium-activated malate transporter (OsALMT), demonstrated significant differential expression, with 1.8- and -0.58-fold changes, respectively, in RR4-treated roots. The gene expression pattern of OsMS corroborated the data obtained by high-performance liquid chromatography, which showed elevated MA levels in roots (1.52-fold), whereas the levels of MA in root exudates were not altered significantly although expression of OsALMT was reduced. Our results demonstrate that B. subtilis RR4 is chemotactic to MA and can induce biosynthesis of MA in rice roots.

Aims: To study the at-risk rate for Autism Spectrum Disorders (ASD) on a parent-report questionnaire in toddlers between the ages of 16-24 months., Materials and Methods: 6237 toddlers from Kerala, India selected by cluster random sampling were surveyed by community nurses using the Modified Checklist for Autism in Toddlers - Revised (M-CHAT-R) translated to Malayalam and culturally adapted., Results: 5.5% toddlers were at risk on M-CHAT-R and 2.7% on "Best Seven"., Conclusions: M-CHAT-R and its "Best Seven" could be viable community level screening instruments, albeit with further cultural adaptation for a primarily non-English speaking population in India., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Attention is foundational to efficient perception and optimal goal driven behavior. Intact attentional processing is crucial for the development of social and communication skills. Deficits in attention are therefore likely contributors to the core pathophysiology of autism spectrum disorder (ASD). Clinical evidence in ASD is suggestive of impairments in attention and its control, but the underlying mechanisms remain elusive. We examined sustained, spatially divided attention in a prenatal valproic acid (VPA) model of ASD using the 5-choice serial reaction time task (5-CSRTT). As compared to controls, male and female VPA rats had progressively lower accuracy and higher omissions with increasing attentional demands during 5-CSRTT training, and showed further performance decrements when subjected to parametric task manipulations. It is noteworthy that although VPA exposure induced attentional deficits in both sexes, there were task parameter specific sex differences. Importantly, we did not find evidence of impulsivity or motivational deficits in VPA rats but we did find reduced social preference, as well as sensorimotor deficits that suggest pre-attentional information processing impairments. Importantly, with fixed rules, graded difficulty levels, and more time, VPA rats could be successfully trained on the attentional task. To the best of our knowledge, this is the first study examining attentional functions in a VPA model. Our work underscores the need for studying both sexes in ASD animal models and validates the use of the VPA model in the quest for mechanistic understanding of aberrant attentional functions and for evaluating suitable therapeutic targets. Autism Res 2017, 10: 1929-1944. © 2017 International Society for Autism Research, Wiley Periodicals, Inc., Lay Summary: We studied rats prenatally exposed to valproic acid (VPA), an established rodent model of autism. Both male and female VPA rats had a range of attentional impairments with sex-specific characteristics. Importantly, with fixed rules, graded difficulty levels, and more time, VPA rats could be successfully trained on the attentional task. Our work validates the use of the VPA model in the quest for evaluating suitable therapeutic targets for improving attentional performance., (© 2017 International Society for Autism Research, Wiley Periodicals, Inc.)

Aims and Objective: (1) To study the clinical and histological features of oral lichen planus, oral lichenoid reaction (OLR) and oral lichenoid dysplasia (OLD). (2) To estimate and compare the silver nucleolar organizer regions in OLR and OLD., Materials and Methods: A total of 40 biopsies were studied; sections were divided as study group, which consists of OLP, OLR and OLD each of 10 cases and 10 biopsies of normal oral mucosa as control group. Sections were stained by silver staining technique and total number of silver stained nucleolar organizer regions (AgNORs) were counted in nucleoli of 100 cells in each section under x100 objective (oil immersion)., Results: Our study revealed that the difference between the (AgNOR) count of OLP (2.272 ± 0.09) and OLR (2.27 ± 0.073) is not statistically significant ( P = 0.81). The mean AgNOR count of OLD (2.388 ± 0.043) compared to that of OLP (2.272 ± 0.09) and OLR (2.27 ± 0.073) showed an increase and it is statistically highly significant ( P = 0.002 and P = 0.003, respectively)., Conclusion: AgNOR count is an objective test, which has stronger biological basis for diagnosing epithelial dysplasia. It is easy to perform, inexpensive and is performed on biopsied specimen. However, this technique cannot differentiate OLP and OLR, as there is no much difference in the proliferative activity of cells in these two lesions. It is reasonable to suggest that all biopsy tissues from lichenoid lesions where dysplastic features are observed in routine histopathological sections should be additionally stained by silver technique to ascertain dysplastic status of the lesion., Clinical Significance: This is an improved diagnostic parameter, which will help pathologists to formulate more definitive final histopathological diagnosis and will in turn facilitate the formulation of patient treatment and follow-up care by clinicians., Competing Interests: There are no conflicts of interest.

We report the magnetic and dielectric behavior of Pb 6 Ni 9 (TeO 6 ) 5 , a new compound comprising the honeycomb-like layers of S = 1 spins, through detailed structural, magnetic and dielectric investigation. An antiferromagnetic-type transition at 25 K (T N ) with weak-ferromagnetic behavior is revealed. Interestingly, a large value of coercive field of 1.32 T at 2 K is observed. The isothermal magnetization after zero-field-cooled condition, it exhibits the presence of large spontaneous exchange bias (SEB) with a magnitude of 0.19 T at 2 K; which is rare in single bulk materials, especially without external doping. The value of |H EB | further enhances to 0.24 T under 16 T field-cooled condition, confirming the presence of large exchange bias in the material.

Background: There is a recent trend of increase in diagnosis of Autism Spectrum Disorder in India. Till date, there are few retrospective and prospective Indian studies with limited sample sizes ranging from 16 to 94 children. With this background, we planned a retrospective chart review of all new cases of Autism Spectrum Disorder for a period of 1 year in our tertiary care child psychiatry centre., Methodology: Objectives of this study were to compare the sociodemographic and clinical profile of children below and above 3 years of age and between those who were self-referred versus those referred by professionals., Results: Out of a total of 1957 case records, 201 children (10.3%) were diagnosed with Autism Spectrum Disorder. Male to female ratio was 4:1.2. Mean age of consultation was significantly higher in males. Seventy six percent had a comorbid disorder with Intellectual disability, Attention Deficit Hyperactivity Disorder and Epilepsy being the most common comorbidities. Most caregivers (92.5%) recognized symptoms by 3 years of age. Presenting complaint of poor social response was more prevalent in children <3 years and co-morbidities in children above 3 years. Presenting complaint of speech delay was more common in children who were referred by professionals when compared with those who were self-referred., Discussion: There is a need to sensitize parents and professionals for early intervention and to standardize protocols for assessment and intervention., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Autism spectrum disorders (ASD) are well known to be influenced by various environmental factors. Among these influencers, social experiential deprivation (SED) in infancy is one of them which is not well reported. We explored factors contributing to SED in 11 young children diagnosed to have ASD and compared them to 24 children without SED also having ASD. Intervention mainly addressing factors causing SED for 6 months demonstrated that children with SED had a better outcome at follow up. Could SED be a possible prognostic factor in children with ASD?, (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To assess the prevalence of neurodevelopmental and psychiatric co-morbidities in children and adolescents diagnosed with attention-deficit hyperactivity disorder at a tertiary care child and adolescent psychiatry centre., Methods: A total of 63 children and adolescents who were diagnosed with attention-deficit hyperactivity disorder and fulfilled the inclusion criteria were comprehensively assessed for neurodevelopmental and psychiatric co-morbidities. The tools used included the Mini-International Neuropsychiatric Interview for Children and Adolescents, Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHD-RS), Children's Global Assessment Scale, Clinical Global Impression Scale, Vineland Social Maturity Scale, and Childhood Autism Rating Scale., Results: All except 1 subject had neurodevelopmental and / or psychiatric disorder co-morbid with attention-deficit hyperactivity disorder; 66.7% had both neurodevelopmental and psychiatric disorders. Specific learning disability was the most common co-existing neurodevelopmental disorder and oppositional defiant disorder was the most common psychiatric co-morbidity. The mean baseline ADHD-RS scores were significantly higher in the group with psychiatric co-morbidities, especially in the group with oppositional defiant disorder., Conclusion: Co-morbidity is present at a very high frequency in clinic-referred children diagnosed with attention-deficit hyperactivity disorder. Psychiatric co-morbidity, specifically oppositional defiant disorder, has an impact on the severity of attention-deficit hyperactivity disorder. Co-morbidity needs to be explicitly looked for during evaluation and managed appropriately.