Browsing by Author "Jan, Reem Kais"

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Anti-Inflammatory Effects of Compounds from Echinoderms
(2022-11) Ghelani, Hardik; Khursheed, Md; Adrian, Thomas E; Jan, Reem Kais
Abstract: Chronic inflammation can extensively burden a healthcare system. Several synthetic anti-inflammatory drugs are currently available in clinical practice, but each has its own side effect profile. The planet is gifted with vast and diverse oceans, which provide a treasure of bioactive compounds, the chemical structures of which may provide valuable pharmaceutical agents. Marine organisms contain a variety of bioactive compounds, some of which have anti-inflammatory activity and have received considerable attention from the scientific community for the development of anti-inflammatory drugs. This review describes such bioactive compounds, as well as crude extracts (published during 2010-2022) from echinoderms: namely, sea cucumbers, sea urchins, and starfish. Moreover, we also include their chemical structures, evaluation models, and anti-inflammatory activities, including the molecular mechanism(s) of these compounds. This paper also highlights the potential applications of those marine-derived compounds in the pharmaceutical industry to develop leads for the clinical pipeline. In conclusion, this review can serve as a well-documented reference for the research progress on the development of potential anti-inflammatory drugs from echinoderms against various chronic inflammatory conditions.
A Biofeedback-Based Mobile App With Serious Games for Young Adults With Anxiety in the United Arab Emirates: Development and Usability Study
(2022-08) Jan, Reem Kais
Background: Following the outbreak of COVID-19, several studies have reported that young adults encountered a rise in anxiety symptoms, which could negatively affect their quality of life. Promising evidence suggests that mobile apps with biofeedback, serious games, breathing exercises, and positive messaging, among other features, are useful for anxiety self-management and treatment. Objective: This study aimed to develop and evaluate the usability of a biofeedback-based app with serious games for young adults with anxiety in the United Arab Emirates (UAE). Methods: This study consists of two phases: Phase I describes the design and development of the app, while Phase II presents the results of a usability evaluation by experts. To elicit the app’s requirements during Phase I, we conducted (1) a survey to investigate preferences of young adults in the UAE for mobile games for stress relief; (2) an analysis of serious games for anxiety; and (3) interviews with mental health professionals and young adults in the UAE. In Phase II, five experts tested the usability of the developed app using a set of Nielsen’s usability heuristics. Results: A fully functional biofeedback-based app with serious games was co-designed with mental health professionals. The app included 4 games (ie, a biofeedback game, card game, arcade game, and memory game), 2 relaxation techniques (ie, a breathing exercise and yoga videos), and 2 additional features (ie, positive messaging and a mood tracking calendar). The results of Phase II showed that the developed app is efficient, simple, and easy to use. Overall, the app design scored an average of 4 out of 5. Conclusions: The elicitation techniques used in Phase I resulted in the development of an easy-to-use app for the self-management of anxiety. Further research is required to determine the app’s usability and effectiveness in the target population.
A Conceptual Framework to Design Connected Mental Health Solutions in the United Arab Emirates: Questionnaire Study
(2022) Jan, Reem Kais
Background: Connected mental health (CMH) is a field presenting information and communications technology–based mental care interventions that could help overcome many mental care delivery barriers. Culture and background influence people’s attitudes, preferences, and acceptance of such solutions. Therefore, the suitability of CMH solutions to the targeted population is an important factor in their successful adoption. Objective: The aim of this study is to develop a framework for the design and creation of CMH solutions suitable for the UAE context. The framework is based on investigating enablers and barriers of CMH adoption in the United Arab Emirates, from the mental health professional's (MHP) perspective and from related literature. Methods: A survey of literature on relevant studies addressing the use of technology for mental care in Arab countries, and a web-based questionnaire-based survey with 17 MHPs practicing in the United Arab Emirates investigating their attitudes and views toward CMH was conducted. Results from the questionnaire and from related studies were analyzed to develop the design framework. Results: On the basis of findings from the literature survey and analyzing MHP answers to the web-based survey, a framework for the design of CMH solutions for the UAE population was developed. The framework presents four types of recommendation categories: favorable criteria, which included blended care, anonymity, and ease of use; cultural factors including availability in multiple languages, mainly Arabic and English, in addition to religious and cultural considerations; technical considerations, including good-quality communication, availability in formats compatible with mobile phones, and providing technical support; and users’ health and data safety considerations, including users’ suitability testing, confidentiality, and ensuring MHP integrity. Conclusions: CMH has the potential to help overcome many mental care barriers in the United Arab Emirates in particular and in the Arab world in general. CMH adoption in the United Arab Emirates has a potential for success. However, many factors should be taken into account, mainly cultural, religious, and linguistic aspects.
Early alterations of large-scale brain networks temporal dynamics in young children with autism
(2021) Jan, Reem Kais
Abstract: Autism spectrum disorders (ASD) are associated with disruption of large-scale brain network. Recently, we found that directed functional connectivity alterations of social brain networks are a core component of atypical brain development at early developmental stages in ASD. Here, we investigated the spatio-temporal dynamics of whole-brain neuronal networks at a subsecond scale in 113 toddlers and preschoolers (66 with ASD) using an EEG microstate approach. We first determined the predominant microstates using established clustering methods. We identified five predominant microstate (labeled as microstate classes A–E) with significant differences in the temporal dynamics of microstate class B between the groups in terms of increased appearance and prolonged duration. Using Markov chains, we found differences in the dynamic syntax between several maps in toddlers and preschoolers with ASD compared to their TD peers. Finally, exploratory analysis of brain–behavioral relationships within the ASD group suggested that the temporal dynamics of some maps were related to conditions comorbid to ASD during early developmental stages.
Early alterations of social brain networks in young children with autism
(2018) Jan, Reem Kais
Abstract:‎ Social impairments are a hallmark of Autism Spectrum Disorders (ASD), but empirical evidence for early ‎brain network alterations in response to social stimuli is scant in ASD. We recorded the gaze patterns ‎and brain activity of toddlers with ASD and their typically developing peers while they explored dynamic ‎social scenes. Directed functional connectivity analyses based on electrical source imaging revealed ‎frequency specific network atypicalities in the theta and alpha frequency bands, manifesting as ‎alterations in both the driving and the connections from key nodes of the social brain associated with ‎autism. Analyses of brain-behavioural relationships within the ASD group suggested that compensatory ‎mechanisms from dorsomedial frontal, inferior temporal and insular cortical regions were associated with ‎less atypical gaze patterns and lower clinical impairment. Our results provide strong evidence that ‎directed functional connectivity alterations of social brain networks is a core component of atypical brain ‎development at early stages of ASD.‎
Editorial: Highlights in women's mental health 2021/22
(2023) Jan, Reem Kais
Introduction: The Research Topic Highlights in Women’s Mental Health 2021/22 was designed to showcase a selection of high-impact articles across the field of women’s mental health—not grouped by content, but rather representative of the breadth of research in this growing field.
Editorial: Women in psychiatry 2022: Psychopharmacology
(2023) Jan, Reem Kais
Introduction: Still a male-dominated field, science has often undervalued the work of women. We are not equally represented at higher career levels and face more professional obstacles than our male counterparts. One among many examples, Rosalind Franklin’s name is the first that come to mind. In the discovery of the DNA double helix, despite her crucial X-ray diffraction work, she never got the same recognition as her male counterparts Watson and Crick.
High-fidelity simulation versus case-based tutorial sessions for teaching pharmacology: Convergent mixed methods research investigating undergraduate medical students' performance and perception
(2024-08) Kaddoura, Rachid; Faraji, Hanan; Otaki, Farah; Radhakrishnan, Rajan; Stanley, Adrian; Jackson, Lisa; Mascarenhas, Sharon; Sudhir, Meghana; Alfroukh, Jalal; Ghelani, Hardik; Azar, Aida Joseph; Khamis, Amar Hassan; Jan, Reem Kais; Al Jayyousi, Reem
Abstract Introduction: Medical educators strive to improve their curricula to enhance the student learning experience. The use of high-fidelity simulation within basic and clinical medical science subjects has been one of these initiatives. However, there is paucity of evidence on using simulation for teaching pharmacology, especially in the Middle East and North Africa region, and the effectiveness of this teaching modality, relative to more traditional ones, have not been sufficiently investigated. Accordingly, this study compares the effects of high-fidelity simulation, which is designed in alignment with adult and experiential learning theories, and traditional case-based tutorial sessions on the performance and perception of undergraduate Year 2 medical students in pharmacology in Dubai, United Arab Emirates. Methods: This study employed a convergent mixed methods approach. Forty-nine medical students were randomly assigned to one of two groups during the 16-week pharmacology course. Each group underwent one session delivered via high-fidelity simulation and another via a case-based tutorial. A short multiple-choice question quiz was administered twice (immediately upon completion of the respective sessions and 5 weeks afterwards) to assess knowledge retention. Furthermore, to explore the students' perceptions regarding the two modes of learning delivery (independently and in relation to each other), an evaluation survey was administered following the delivery of each session. Thereafter, the iterative joint display analysis was used to develop a holistic understanding of the effect of high-fidelity simulation in comparison to traditional case-based tutorial sessions on pharmacology learning in the context of the study. Results: There was no statistically significant difference in students' knowledge retention between high-fidelity simulation and case-based tutorial sessions. Yet, students expressed a greater preference for high-fidelity simulation, describing the corresponding sessions as more varied, better at reinforcing learning, and closer to reality. As such, the meta-inferences led to expansion of the overall understanding around students' satisfaction, to both confirmation and expansion of the systemic viewpoint around students' preferences, and lastly to refinement in relation to the perspective around retained knowledge. Conclusion: High-fidelity simulation was found to be as effective as case-based tutorial sessions in terms of students' retention of knowledge. Nonetheless, students demonstrated a greater preference for high-fidelity simulation. The study advocates caution in adapting high-fidelity simulation, where careful appraisal can lend itself to identifying contexts where it is most effective.
Identification of Specific Biomarkers and Pathways in the Treatment Response of Infliximab for Inflammatory Bowel Disease: In-Silico Analysis
(2023) Kaddoura, Rachid; Ghelani, Hardik; Alqutami, Fatma; Altaher, Hala; Hachim, Mahmood Yaseen; Jan, Reem Kais
Background: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. In biological therapy, infliximab became the first anti-tumor necrosis factor (TNF) agent approved for IBD. Despite this success, infliximab is expensive, often ineffective, and associated with adverse events. Prediction of infliximab resistance would improve overall potential outcomes. Therefore, there is a pressing need to widen the scope of investigating the role of genetics in IBD to their association with therapy response. Methods: In the current study, an in-silico analysis of publicly available IBD patient transcriptomics datasets from Gene Expression Omnibus (GEO) are used to identify subsets of differentially expressed genes (DEGs) involved in the pathogenesis of IBD and may serve as potential biomarkers for Infliximab response. Five datasets were found that met the inclusion criteria. The DEGs for datasets were identified using limma R packages through the GEOR2 tool. The probes’ annotated genes in each dataset intersected with DGEs from all other datasets. Enriched gene Ontology Clustering for the identified genes was performed using Metascape to explore the possible connections or interactions between the genes. Results: 174 DEGs between IBD and healthy controls were found from analyzing two datasets (GSE14580 and GSE73661), indicating a possible role in the pathogenesis of IBD. Of the 174 DEGs, five genes (SELE, TREM1, AQP9, FPR2, and HCAR3) were shared between all five datasets. Moreover, these five genes were identified as downregulated in the infliximab responder group compared to the non-responder group. Conclusions: We hypothesize that alteration in the expression of these genes leads to an impaired response to infliximab in IBD patients. Thus, these genes can serve as potential biomarkers for the early detection of compromised infliximab response in IBD patients.
Neural Processing of Dynamic Animated Social Interactions in Young Children With Autism Spectrum Disorder: A High-Density Electroencephalography Study
(2019-08-22) Jan, Reem Kais
Background: Atypical neural processing of social visual information contributes to impaired social cognition in autism spectrum disorder. However, evidence for early developmental alterations in neural processing of social contingencies is scarce. Most studies in the literature have been conducted in older children and adults. Here, we aimed to investigate alterations in neural processing of social visual information in children with autism spectrum disorder compared to age-matched typically developing peers. Methods: We used a combination of 129-channel electroencephalography and high-resolution eye-tracking to study differences in the neural processing of dynamic cartoons containing human-like social interactions between 14 male children with autism spectrum disorder and 14 typically developing male children, aged 2–5 years. Using a microstate approach, we identified four prototypical maps in both groups and compared the temporal characteristics and inverse solutions (activation of neural sources) of these maps between groups. Results: Inverse solutions of the group maps that were most dominant during free viewing of the dynamic cartoons indicated decreased prefrontal and cingulate activation, impaired activation of the premotor cortex, and increased activation of parietal, temporal, occipital, and cerebellar regions in children with autism spectrum disorder compared to their typically developing peers. Conclusions: Our findings suggest that impairments in brain regions involved in processing social contingencies embedded in dynamic cartoons are present from an early age in autism spectrum disorder. To the best of our knowledge, this is the first study to investigate neural processing of social interactions of children with autism spectrum disorder using dynamic semi-naturalistic stimuli.
Nigella sativa and its chemical constituents: pre clinical and clinical evidence for their potential anti SARS CoV 2 effects
(2023) Cyril, Asha Caroline; Ali, Najma Mohamed; Parambath, Anagha Nelliyulla; Jan, Reem Kais; Radhakrishnan, Rajan; Karuvantevida, Noushad; Aburamadan, Haneen
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 500 million reported cases of COVID-19 worldwide with relatively high morbidity and mortality. Although global vaccination drive has helped control the pandemic, the newer variant of the virus still holds the world in ransom. Several medicinal herbs with antiviral properties have been reported, and one such promising herb is Nigella sativa (NS). Recent molecular docking, pre-clinical, and clinical studies have shown that NS extracts may have the potential to prevent the entry of coronaviruses into the host cell as well as to treat and manage COVID-19 symptoms. Several active compounds from NS, such as nigelledine, α-hederin, dithymoquinone (DTQ), and thymoquinone (TQ), have been proposed as excellent ligands to target angiotensin-converting enzyme 2 (ACE2 receptors) and other targets on host cells as well as the spike protein (S protein) on SARS-CoV-2. By binding to these target proteins, these ligands could potentially prevent the binding between ACE2 and S protein. Though several articles have been published on the promising therapeutic role of NS and its constituents against SARS-CoV-2 infection, in this review, we consolidate the published information on NS and SARS-CoV-2, focusing on pre-clinical in silico studies as well as clinical trials reported between 2012 and 2023.
Outcomes of guideline-based medical therapy in patients with acute heart failure and reduced left ventricular ejection fraction Observations from the Gulf acute heart failure registry (Gulf CARE)
(2022) Jan, Reem Kais; Alsheikh-Ali, Alawi
Abstract: This study aimed to report on the use, predictors and outcomes of guideline-based medical therapy (GBMT) in patients with acute heart failure (HF) with reduced ejection fraction of 40% (HFrEF), from seven countries in the Arabian Gulf. Patients with acute HFrEF (N=2680), aged 18 years or older, and hospitalized February–November 2012 were recruited and data were collected post discharge at 3months (n=2477) and 1 year (n=2418). The use and doses of GBMT were evaluated as per European, American and Canadian HF guidelines. Analyses were performed using multivariate logistic regression. This study was registered at clinicaltrials.gov (NCT01467973). The majority of patients were on dual (39%) and triple (39%) GBMT modalities, 14% received one GBMT medication, while 7.2% were not on any GBMT medications. On admission, 80% of patients were on renin-angiotensin system (RAS) blockers, 75% on bblockers and 56% on mineralocorticoid receptor antagonists (MRAs), with a small proportion of these patients were taking target doses (RAS blockers 13%, b-blockers 7.3%, MRAs 14%). Patients taking triple GBMT were younger (P <. 001), less likely to have comorbidities such as diabetes mellitus (P <.001 1) and CKD/dialysis (P < 001), less likely to receive in-hospital invasive treatments (P < .001), and more likely to be treated by a cardiologist (P <. .001), than patients on a single medication. Patients taking triple GBMT showed significantly reduced all-cause mortality both at 3-months (P=.048), and at 12-months (P=.003), compared to patients taking no GBMT. Triple GBMT prescribing and dosing in patients with HFrEF were suboptimal in the Arabian Gulf. Further studies are required to investigate GBMT utilization and dosing in the outpatient setting.
Pain in chronic prostatitis and the role of ion channels: a brief overview
(2021) Cyril, Asha Caroline; Jan, Reem Kais; Radhakrishnan, Rajan
Background: Prostatitis is the third most common urologic condition affecting more than half the male population at some point in their lives. There are different categories of prostatitis, of which approximately 90% of cases can be classified under the National Institute of Health (NIH) type III category (chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS)) with no causative agents identified. CP/CPPS is associated with several symptoms, of which the most prominent being chronic pain. Despite its high incidence, pain management in patients with CP/CPPS has been poor, possibly due to the lack of understanding of aetiological factors and mechanisms underlying pain development. Methods: An extensive literature search of published articles on the molecular mechanisms of pain in CP/CPPS was conducted using PubMed and Google Scholar search engines (https://pubmed.ncbi.nlm.nih.gov and https://scholar.google.com). The terms used for the search were: prostatitis, pain mechanism in CP/CPPS, prostatitis pain models, acid-sensing ion channels (ASICs), transient receptor potential vanilloid type 1 (TRPVs), purinergic channels (P2X) in prostatitis pain mechanism and inflammatory mediators in CP/CPPS. The papers were identified based on the title and abstract, and after excluding the articles that did not emphasize the pain mechanism in CP/CPPS. Ninety-five articles (36 review and 59 original research papers) met our criteria and were included in the review. Results: A number of inflammatory mediator molecules and pain channels, including ASICs, transient receptor potential vanilloid channels (TRPVs) and P2Xs have been investigated for their role in prostatitis pain pathology using various animal models. Conclusion: This review summarizes the pain mechanisms in CP/CPPS focusing on the inflammatory mediators, neurotransmitters, pain-transducing ion channels and small animal models developed for studying prostatitis.
Study protocol for a pilot randomized, double-blind, placebo-controlled trial to investigate the anti-inflammatory effects of Frondanol in adults with inflammatory bowel disease
(2022-12) Ghelani, Hardik; Adrian, Thomas E; Ho, Samuel B; Akhras, Jamil; Azar, Aida J; Jan, Reem Kais
Introduction: Inflammatory bowel disease (IBD), consisting of Crohn's disease and ulcerative colitis, is a debilitating condition with a rising incidence globally over recent years. Frondanol, a widely available nutraceutical extract of the edible sea cucumber Cucumaria frondosa has been reported to possess potent anti-inflammatory effects, likely mediated by the inhibition of 5-lipoxygenase and 12-lipoxygenase pathways, whilst showing no signs of toxicity. The potent anti-inflammatory effects of Frondanol in a mouse model of IBD provide encouragement for investigating its effects in human IBD patients. Here we describe the study protocol of a pilot randomized, double-blinded, placebo-controlled trial of Frondanol in patients with mild to moderate IBD who are on standard therapy. Material and methods: One hundred patients will be randomized (1:1) to receive Frondanol or placebo as an adjunct to their standard therapy for the period of six months. Blood and stool samples will be obtained during routine visits at baseline, and after three months and six months of treatment, and tissue samples from colon biopsies will be obtained during clinically indicated colonoscopies at baseline and after six months of treatment. The levels of inflammatory markers will be compared in serum and tissue samples between patients treated with Frondanol and those treated with placebo, and findings will be correlated with clinical and histological parameters. Discussion: If proven beneficial, treatment with Frondanol may increase the likelihood of patients remaining in remission and potentially provide an effective, natural and safe addition/alternative for treatment-naive patients in the future.(Clinical trial registration number: NCT05194007).
Unraveling the developmental dynamic of visual exploration of social interactions in autism
(2023-12) Jan, Reem Kais
Abstract: Atypical deployment of social gaze is present early on in toddlers with autism spectrum disorders (ASDs). Yet, studies characterizing the developmental dynamic behind it are scarce. Here, we used a data-driven method to delineate the developmental change in visual exploration of social interaction over childhood years in autism. Longitudinal eye-tracking data were acquired as children with ASD and their typically developing (TD) peers freely explored a short cartoon movie. We found divergent moment-to-moment gaze patterns in children with ASD compared to their TD peers. This divergence was particularly evident in sequences that displayed social interactions between characters and even more so in children with lower developmental and functional levels. The basic visual properties of the animated scene did not account for the enhanced divergence. Over childhood years, these differences dramatically increased to become more idiosyncratic. These findings suggest that social attention should be targeted early in clinical treatments.
Using publicly available datasets to identify population-based transcriptomic landscape contributing to the aggressiveness of breast cancer in young women
(2023) Tabbal, Marah; Hachim, Mahmood Yaseen; Jan, Reem Kais; Adrian, Thomas E
Introduction: Although the risk of breast cancer increases with advancing age, some regions have larger number of young breast cancer patients (≤45 years old), such as the Middle East, Eastern Asia, and North Africa, with more aggressive and poorly differentiated tumors. We aimed to conduct an in-silico analysis in an attempt to understand the aggressive nature of early-onset breast cancer, and to identify potential drivers of early-onset breast cancer using gene expression profiling datasets in a population-dependent manner. Methods: Functional genomics experiments data were acquired from cBioPortal database for cancer genomics, followed by the stratification of patients based on the age at representation of breast cancer and race. Differential gene expression analysis and gene amplification status analysis were carried out, followed by hub gene, transcription factor, and signalling pathway identification. Results: PAM50 subtype analysis revealed that young patients (≤45 years-old) had four-fold more basal tumors and worst progression-free survival (median of 101 months), compared with the 45–65 years group (median of 168 months). Fourteen genes were amplified in more than 14% of patients with an early-onset breast cancer. Interestingly, FREM2, LINC00332, and LINC00366 were exclusively amplified in younger patients. Gene expression data from three different populations (Asian, White, and African) revealed a unique transcriptomic profile of young patients, which was also reflected on the PAM50 subtype analysis. Our data indicates a higher tendency of young African patients to develop basal tumors, while young Asian patients are more prone to developing Luminal A tumors. Most genes that were found to be upregulated in younger patients are involved in important signaling pathways that promote cancer progression and metastasis, such as MAPK pathway, Reelin pathway and the PI3K/Akt pathway. Conclusion: This study provides strong evidence that the molecular profile of tumors derived from young breast cancer patients of different populations is unique and may explain the aggressiveness of these tumors, stressing the need to conduct population- based multi-omic analyses to identify the potential drivers for tumorigenesis and molecular profiles of young breast cancer patients.