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IntroductionFamilial hypercholesterolemia, the highly prevalent form of dyslipidemia, is a well-known risk factor for premature heart disease and stroke worldwide. Statins, which inhibit 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, are the first-choice treatment for dyslipidemias, and have been effective in reducing the risk of stroke and myocardial infarction. However, emerging evidence indicates that statins may increase the incidence of new-onset type 2 diabetes by reducing β-cell mass and function. Notably, past in vitro reports studying the effects of statins on β-cells were performed without including free fatty acids in the model. This factor should have been addressed since these agents are used to treat individuals with hyperlipidemia.MethodsHere, we used a mouse insulinoma MIN6 β-cell culture model to assess the efficacy, cytotoxicity, and insulin-suppressive effects of simvastatin and pravastatin in the presence of palmitic, linoleic, and oleic acids cocktail to mimic mixed lipids challenge in a biologically relevant setting.Results and discussionOur findings indicate that simvastatin was more effective in lowering intracellular cholesterol but was more cytotoxic as compared to pravastatin. Similarly, simvastatin exhibited a higher suppression of total insulin content and insulin secretion. Both drugs suppressed insulin secretion in phases 1 and 2, dose-dependently. No significant effect was observed on mitochondrial respiration. More importantly, elution experiments showed that insulin content diminution by simvastatin treatment was reversible, while exogenous mevalonate did not improve total insulin content. This suggests that simvastatin's influence on insulin content is independent of its specific inhibitory action on HMG-CoA reductase. In conclusion, our study identified that simvastatin was more effective in lowering intracellular cholesterol, albeit it was more toxic and suppressive of β-cells function. Notably, this suppression was found to be reversible.

BackgroundDengue virus (DENV) infection, spread by Aedes aegypti mosquitoes, is a significant public health concern in tropical and subtropical regions. Among the four distinct serotypes of DENV (DENV-1 to DENV-4), DENV-2 is associated with the highest number of fatalities worldwide. However, there is no specific treatment available for dengue patients caused by DENV-2.ObjectiveThis study aimed to identify inhibitory phytocompounds in silico in Vernonia cinerea (V. cinerea), a widely used traditional medicinal plant, for treating DENV-2 associated illnesses.MethodsThe chemical structures of 17 compounds from V. cinerea were sourced from the Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) database. These compounds underwent geometry optimization, were screened against nonstructural protein 1 (NSP1) of DENV-2, and further validated through molecular dynamics simulations (MDS). Baicalein, an established drug against DENV-2, was used for validation in molecular screening, MDS, and MM-GBSA analyses.ResultsAmong these compounds, Beta-amyrin, Beta-amyrin acetate, Chrysoeriol, Isoorientin, and Luteolin showed promising potential as inhibitors of the NSP1 of DENV-2, supported by the results of thermodynamic properties, molecular orbitals, electrostatic potentials, spectral data and molecular screening. Besides, these compounds adhered to the Lipinski’s “rule of 5”, showing no hepatotoxicity/cytotoxicity, with mixed mutagenicity, immunotoxicity, and carcinogenicity. Furthermore, final validation through MDS confirmed their potential, demonstrating stable tendencies with significant inhibitory activities against NSP1 of DENV-2 over the control drug Baicalein. Among the screened compounds, Chrysoeriol emerged as the most promising inhibitor of NSP1 of DENV-2, followed by Luteolin and Isoorientin.ConclusionTaken together, our results suggest that Chrysoeriol is the best inhibitor of NSP1 of DENV-2, which could be evaluated as a therapeutic agent or a lead compound to treat and manage DENV-2 infections.

BackgroundThe Kuwaiti and Qatari populations have a high prevalence of obesity, a major risk factor for various metabolic disorders. Previous studies have independently explored mitochondrial DNA (mtDNA) variations and their association with obesity in these populations. This study aims to investigate the role of mtDNA haplogroups and variants in obesity risk among these Gulf populations.MethodsWhole exome sequencing data from 1,112 participants (348 Kuwaitis and 764 Qataris) were analyzed for mtDNA variants. Participants were classified as obese or non-obese based on body mass index (BMI). Association analyses were performed to examine the relationship between mtDNA haplogroups and obesity, adjusting for covariates such as age and sex.ResultsHaplogroup R was found to be protective against obesity, with an odds ratio (OR) of 0.69 (p = 0.045). This association remained significant after adjusting for age and sex (OR = 0.694; 95% CI: 0.482-0.997; p = 0.048). Several mtDNA variants, particularly those involved in mitochondrial energy metabolism, showed nominal associations with obesity, but these did not remain significant after correcting for multiple testing.ConclusionHaplogroup R consistently demonstrates a protective association against obesity in both Kuwaiti and Qatari populations, highlighting its potential as a biomarker for obesity risk in the Gulf region. However, further research with larger sample sizes is needed to validate these findings and clarify the role of mtDNA variants in obesity.

IntroductionIncreasing evidence from human and animal model studies indicates the significant role of microRNAs (miRNAs) in pancreatic beta cell function, insulin signaling, immune responses, and pathogenesis of type 1 diabetes (T1D).MethodsWe aimed, using next-generation sequencing, to screen miRNAs from peripheral blood mononuclear cells of eight independent Kuwaiti-Arab families with T1D affected siblings, consisting of 18 T1D patients and 18 unaffected members, characterized by no parent-to-child inheritance pattern.ResultsOur analysis revealed 20 miRNAs that are differentially expressed in T1D patients compared with healthy controls. Module-based weighted gene co-expression network analysis prioritized key consensus miRNAs in T1D pathogenesis. These included hsa-miR-320a-3p, hsa-miR-139-3p, hsa-miR-200-3p, hsa-miR-99b-5p and hsa-miR-6808-3p. Functional enrichment analysis of differentially expressed miRNAs indicated that PI3K-AKT is one of the key pathways perturbed in T1D. Gene ontology analysis of hub miRNAs also implicated PI3K-AKT, along with mTOR, MAPK, and interleukin signaling pathways, in T1D. Using quantitative RT-PCR, we validated one of the key predicted miRNA-target gene-transcription factor networks in an extended cohort of children with new-onset T1D positive for islet autoantibodies. Our analysis revealed that hsa-miR-320a-3p and its key targets, including PTEN, AKT1, BCL2, FOXO1 and MYC, are dysregulated in T1D, along with their interacting partners namely BLIMP3, GSK3B, CAV1, CXCL3, TGFB, and IL10. Receiver Operating Characteristic analysis highlighted the diagnostic potential of hsa-miR-320a-3p, CAV1, GSK3B and MYC for T1D.DiscussionOur study presents a novel link between hsa-miR-320a-3p and T1D, and highlights its key regulatory role in the network of mRNA markers and transcription factors involved in T1D pathogenesis.

Objective: This study explores the frequency of human leukocyte antigen (HLA) genes, particularly HLA-B alleles, within the Kuwaiti population. We aim to identify alleles with known associations to adverse drug reactions (ADRs) based on existing literature. We focus on the HLA-B gene due to its well-documented associations with severe cutaneous adverse reactions and the extensive pharmacogenetic research supporting its clinical relevance.MethodsWe utilized the HLA-HD tool to extract, annotate, and analyse HLA-B alleles from the exome data of 561 Kuwaiti individuals, sequenced on the Illumina HiSeq platform. HLA typing was conducted using the HLA-HD tool with a reference panel from the IPD-IMGT/HLA database. The major HLA-B pharmacogenetic markers were obtained from the HLA Adverse Drug Reaction Database, focusing on alleles with significant ADR associations in published literature.ResultsThe distribution of HLA-B alleles in the Kuwaiti population revealed that the most frequent alleles were HLA-B*50:01 (10.52%), HLA-B*51:01 (9.89%), HLA-B*08:01 (6.06%), HLA-B*52:01 (4.55%), HLA-B*18:01 (3.92%), and HLA-B*41:01 (3.65%). Notably, alleles HLA-B*13:01, HLA-B*13:02, HLA-B*15:02, HLA-B*15:13, HLA-B*35:02, HLA-B*35:05, HLA-B*38:01, HLA-B*40:02, HLA-B*44:03, HLA-B*51:01, HLA-B*57:01 and HLA-B*58:01 were identified with known associations to various ADRs. For example, HLA-B*51:01 was associated with clindamycin, phenobarbital, and phenytoin, and was found in 18% of individuals.ConclusionOur study enriches the regional genetic landscape by delineating HLA-B allele variations within Kuwait and across the Arabian Peninsula. This genetic insight, along with the identification of markers previously linked to drug hypersensitivity, provides a foundation for future pharmacogenetic research and potential personalized medicine strategies in the region.

Background Reduced estimated glomerular filtration rate (eGFR) is associated with lower use of invasive management and increased mortality after acute coronary syndrome (ACS). The reasons for this are unclear.Methods A retrospective clinical cohort study was performed using data from the English National Institute for Health Research Health Informatics Collaborative (2010–2017). Multivariable logistic regression was used to investigate whether eGFR

The study proposed the removal of Brilliant Green, a cationic dye, by adsorption process from wastewater solution utilizing a low-cost adsorbent such as Nutraceutical Industrial Pepper Seed Spent (NIPSS). The study comprises an investigation of the parametric influence on the adsorption process. The parameters identified are pH, dye concentration, process temperature, quantity of the adsorbent, and particle size. The study of statistics found from experiments was carried out by incorporating Freundlich, Brouers-Sotolongo, Langmuir, Toth, Sips, Jovanovic, and Redlich-Peterson isotherm models. The adsorption kinetics were determined by implementing pseudo-first-order and second-order models, diffusion film models, and Dumwald-Wagner and Weber-Morris models. The experimental adsorption capacity qe was found to be about 130 mg/g. This value was closest to the maximum adsorption of 144.6mg/g predicted by the Brouers-Sotolongo isotherm which had a correlation coefficient (R2) of 0.998. The adsorption kinetics data was confirmed to be a pseudo-second-order model. The change in free energy, enthalpy change, and entropy change were vital thermodynamic factors in concluding that adsorption is almost spontaneous and endothermic process. Change in enthalpy (ΔH°) reduced value indicates the physical nature of the process. The adsorption of BG dye on the adsorbent surface was authenticated by FTIR spectroscopy and SEM imaging. A Central Composite Design (CCD) Quadratic model under Response Surface Methodology (RSM) was implemented for statistical optimization of adsorption capacity for the five parameters studied, namely, time, temperature, concentration of the dye, weight of the adsorbent, and pH. Software Design Expert 7.0 was used to evaluate 3D contour plots. The process of optimization yielded a value of 350 mg/g. Thus, incrementing the adsorption process by 84.2 %. The study provides insights on various dye and adsorbent interaction possibilities and derives that NIPSS is an efficient adsorbent to extract BG dye from wastewater solutions.

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Introduction: The current research was conducted to estimate the loss of crestal bone using the flap and flapless method for implant placement. Materials and Methods: Forty participants who fulfilled the addition criteria were chosen for this research. All participants were then categorized equally into two study groups, that is, with and without undergoing flap surgery. Statistical evaluation was performed using the Mann-Whitney U-test. Results: Flapless implant placement showed lesser crestal bone loss. Conclusion: Compared to flap surgery, seamless implant implantation showed less loss of crestal bone.

Objectives: This study was conducted to evaluate the efficacy of turmeric, ashwagandha, and aloe vera in the management of oral lichen planus (OLP) lesion. Materials and Methods: Thirty patients with histologically confirmed symptomatic OLP with gingival presentation were included in this comparative investigation. Three groups of participants were created: Group I consisted of turmeric; group II included ashwagandha; and group III included aloe vera. For 3 weeks in a row, they were told to apply topical treatments twice a day. The patients were recalled for 4 to evaluate the cessation of symptoms. Result: The participants in all the groups showed a considerable improvement in the burning lesion size and pain after 4 months of follow-up. Conclusion: For the treatment of OLP, turmeric, ashwagandha, and aloe vera can be useful as substitute topical medications, particularly for those who are not responsive to topical corticosteroids.

Introduction: Oral infections are most frequently caused by three oral microorganisms: Streptococcus mutans (S. mutans), Enterococcus faecalis (E. faecalis), and Candida albicans (C. albicans). Objectives: To evaluate antimicrobial potential of 10% ginger extract (GE) and apple vinegar against S. Mutans, E. faecalis, and C. albicans. Materials and Method: The GE and apple cider vinegar (ACV) were tested for microbiological evaluation to identify the inhibitory zone using the agar disk diffusion test against S. mutans, C. albicans, and E. faecalis. Result: The 10% ethanolic GE and ACV showed a maximum zone of inhibition zone against S. mutans, E. Faecalis, and C. albicans. The intragroup comparison was insignificant. Conclusion: Apple vinegar and 10% ethanolic GE were shown to have good antimicrobial properties against all three tested pathogens.

Creep is a complex behavior of concrete since it induces different stages of response under loading and unloading with time. It represents the time-dependent strain as a result of a constant sustained load applied with time. In cementitious materials such as engineered cementitious composite concrete, ECC, the loaded cement paste is the principal source of creep strain. Therefore, investigating the overall creep behavior, under the loading and unloading stages, will be beneficial in providing data for the performance of ECC concrete. The test for compressional creep strain is done according to the ASTM C- 512 under controlled temperature (21 oC) and relative humidity (40%). In this research, the loading stage lasted for 9 months, and the unloading stage lasted 3 months. The total creep strain, creep coefficient, and specific creep were recorded for six ECC concrete mixes. The mixes have two strength levels, 30 and 60 MPa at 28 days, and contain polypropylene and polyvinyl alcohol fibers. Results revealed significant enhancement, and lower creep behavior, in mixes including fibers compared to plain mixes. The best promising results for the creep coefficient and specific creep were recorded when using mixes of 60 MPa containing polyvinyl alcohol fibers compared to plain mixes.

Abstract Centrin1 gene deleted Leishmania donovani parasite (LdCen1 −/− ) was developed and extensively tested experimentally as an intracellular stage-specific attenuated and immunoprotective live parasite vaccine candidate ex vivo using human PBMCs and in vivo in animals. Here we report manufacturing and pre-clinical evaluation of current Good-Laboratory Practice (cGLP) grade LdCen1 −/− parasites, as a prerequisite before proceeding with clinical trials. We screened three batches of LdCen1 −/− parasites manufactured in bioreactors under cGLP conditions, for their consistency in genetic stability, attenuation, and safety. One such batch was preclinically tested using human PBMCs and animals (hamsters and dogs) for its safety and protective immunogenicity. The immunogenicity of the CGLP grade LdCen1 −/− parasites was similar to one grown under laboratory conditions. The cGLP grade LdCen1 −/− parasites were found to be safe and non-toxic in hamsters and dogs even at 3 times the anticipated vaccine dose. When PBMCs from healed visceral leishmaniasis (VL) cases were infected with cGLP LdCen1 −/− , there was a significant increase in the stimulation of cytokines that contribute to protective responses against VL. This effect, measured by multiplex ELISA, was greater than that observed in PBMCs from healthy individuals. These results suggest that cGLP grade LdCen1 −/− manufactured under cGMP complaint conditions can be suitable for future clinical trials.

Abstract Estimating runoff at ground-mounted solar photovoltaic (PV) installations is challenging because of the disconnected nature of impervious solar panels and the pervious ground surface underneath and between panel rows. There is a need for improved tools to estimate how low impact development practices at these solar installations affect stormwater runoff. The objective of this study was to develop an innovative spreadsheet-based runoff calculator that rapidly estimates stormwater runoff from ground-mounted solar PV sites. The calculator is built on a 2-D hydrologic model (Hydrus-2D/3D) calibrated and validated using experimental data from five commercial solar farms in Colorado, Georgia, Minnesota, New York, and Oregon. The Hydrus-2D/3D hydrologic model was then used to generate nomographs for stormwater runoff that were incorporated into an easy-to-use Excel-based solar farm runoff calculator. This calculator allows for rapid estimation of NRCS stormwater runoff curve number (CN) values at solar farms by considering several complex factors unique to PV installations including: soil and topographic characteristics, surface cover, disconnected impervious surface factors associated with various solar panel designs, and climatic factors. The solar farm runoff calculator quickly estimates runoff CN for pre- and post-construction scenarios, and can estimate actual depth of runoff based on a user-specified 24-h design storm depth. Factors that have the most significant impact on stormwater runoff include design storm return frequency, soil texture, soil bulk density, and soil depth. Ground surface cover has a moderate impact on stormwater runoff, and factors that have a lesser impact on stormwater runoff include slope and array size, spacing and orientation on the landscape. The runoff calculator allows for accurate estimates of runoff generated by disconnected impervious surfaces and low impact development practices at solar farms as affected by a wide range of site-specific conditions.

The aim of this research is to investigate whether construction rubbles may be utilized as coarse aggregates in concrete. Experimentally, the slump, unit weight, compressive, tensile, and flexural strength tests were applied on concrete samples with varying percentages of recycled coarse aggregate (RCA) and compared with reference concrete produced with natural coarse aggregate. This research conducted 96 concrete samples with RCA replacement percentages of 0, 35, 65, and 100%, respectively. The control mixture produced with natural aggregate showed better results than the mixtures containing recycled aggregate; thus, compressive, tensile, and flexural strengths reduced as the amount of the recycled aggregate increased. Using 100% RCA, the compressive, tensile, and flexural strength reduction reached up to 64, 29, and 38%, respectively.

Abstract Topic modeling methods proved to be effective for inferring latent topics from short texts. Dealing with short texts is challenging yet helpful for many real-world applications, due to the sparse terms in the text and the high dimensionality representation. Most of the topic modeling methods require the number of topics to be defined earlier. Similarly, methods based on Dirichlet Multinomial Mixture (DMM) involve the maximum possible number of topics before execution which is hard to determine due to topic uncertainty, and many noises exist in the dataset. Hence, a new approach called the Topic Clustering algorithm based on Levenshtein Distance (TCLD) is introduced in this paper, TCLD combines DMM models and the Fuzzy matching algorithm to address two key challenges in topic modeling: (a) The outlier problem in topic modeling methods. (b) The problem of determining the optimal number of topics. TCLD uses the initial clustered topics generated by DMM models and then evaluates the semantic relationships between documents using Levenshtein Distance. Subsequently, it determines whether to keep the document in the same cluster, relocate it to another cluster, or mark it as an outlier. The results demonstrate the efficiency of the proposed approach across six English benchmark datasets, in comparison to seven topic modeling approaches, with 83% improvement in purity and 67% enhancement in Normalized Mutual Information (NMI) across all datasets. The proposed method was also applied to a collected Arabic tweet and the results showed that only 12% of the Arabic short texts were incorrectly clustered, according to human inspection.

Abstract Background It is crucial to include a wide range of the population in clinical trials for the outcome to be applicable in real-world settings. Existing literature indicates that under-served groups, including disabled people, have been excluded from participating in clinical trials without justification. Exclusion from clinical trials exacerbates disparities in healthcare and diminishes the benefits for excluded populations. Therefore, this study was conducted to investigate potential obstacles that prevent disabled people from participating in clinical trials in the United Kingdom (UK). Methods The study was carried out through an explanatory sequential mixed methods design. The Imperial Clinical Trials Unit devised and implemented an online questionnaire-based survey (with open/closed-ended questions) and an online focus group discussion. The target population were disabled people, family members/carers of disabled people and staff involved in clinical trials, whereupon the sample was recruited by convenience sampling methods via posters and emails through various networks. The Qualtrics XM survey system was used as the host platform for the online survey, and Microsoft Teams was used for an online focus group discussion. The focus group discussion was conducted to gain a deeper understanding of the themes identified from the survey responses. We analysed responses to the survey via descriptive analysis and used thematic analysis to synthesise the free-text answers from the survey and focus group discussion. Results We received 45 responses to the survey questionnaire and 5 disabled people took part in a focus group discussion. Our findings highlighted the differences between the perspectives of researchers and those “being researched” and different types of barriers experienced by disabled people: opportunity barriers (inadequate recruitment strategy and ambiguous eligibility criteria), awareness barriers (perception of disability) and acceptance/refusal barriers (available support and adjustment, and sharing of trial results). Conclusion Our findings support perspectives drawn from the Ford Framework regarding the need to consider all barriers, not just up to the point of enrolment into trials but also beyond the point of inclusion in clinical trials. We support calls for the introduction of legislation on including disabled people in clinical trials, implementation of industry/community-wide participatory approaches and the development of guidelines, a combined public–private approach.

Introduction: Urolithiasis is one of the most common urological problems worldwide. The fastest treatment modality to achieve stone clearance of ureteral stones is Ureteroscopic Lithotripsy (URSL). However, it is negated by both the cost burden and potential risk to the patient. Medical Expulsive Therapy (MET) is a treatment option for upto 10 mm stones but has failure rates of 40-60% in the literature. Aim: To analyse the various indications for surgery, whether MET was used or not, if used-its details, operative findings at ureteroscopy including the reason for the failure of MET. Materials and Methods: A cross-sectional study consisting of 72 patients with ureteric calculi undergoing URSL was analysed from June 2017 to December 2018 at Mazumdar Shaw Medical Centre, Bangalore, Karnataka, India. Indications were assessed at the time of admission. During ureteroscopy, factors like impaction, distal obstruction, and unusual findings were studied, which could have contributed to the failure of MET. The Chi-square test was used as a test of significance for categorical data. The Analysis of Variance (ANOVA) test was used as a test of significance to identify the mean difference between continuous variables. The p-value of

BACKGROUND: Innovative methods of teaching such as problem-based learning (PBL) and case-based learning (CBL) have shown promising results in academic understanding and application and enable one to manage their patients in a better manner. The study aimed to analyze the role of a combination of PBL and CBL teaching methodologies in a dental teaching institute in India. MATERIALS AND METHODS: This prospective, cross-sectional randomized study comprised 500 students divided into two study groups, each consisting of 250 participants. Students in group A were provided PBL, whereas students in group B were exposed to CBL, followed by which questionnaire was distributed. Responses received were analyzed statistically for significance set at below 0.05. RESULTS: In this study, statistical difference in learning methods was observed with organizational capacities, self-process of learning, finding solutions for clinical diagnosis, encouraging self-learning, and developing skills for critical thinking process while comparing the PBL or CBL methodologies. CONCLUSION: According to this study’s findings, improvement in one’s knowledge and clinical skills by a subject is much better when both of these techniques are combined.

Background The primary objective worldwide during the coronavirus disease 2019 (COVID-19) pandemic had been controlling disease transmission. However, lockdown measures used to mitigate transmission affected human behavior and altered lifestyles, with a likely impact on chronic non-communicable diseases. More than a year into the pandemic, substantial peer-reviewed literature emerged on altered lifestyles following the varying lockdown measures imposed globally to control the virus spread. We explored the impact of lockdown measures on six lifestyle factors, namely diet, physical activity, sleep, stress, social connectedness, and the use of tobacco, alcohol, or other harmful substances. Methods We comprehensively searched PubMed and the World Health Organization’s global literature database on COVID-19 and retrieved 649 relevant articles for the narrative review. A critical interpretative synthesis of the articles was performed. Results Most of the articles included in the review identified the negative effect of lockdown measures on each of the lifestyle factors in many parts of the world. Encouraging lifestyle trends were also highlighted in a few articles. Such trends can positively influence the outcome of lifestyle-related chronic diseases, such as obesity and diabetes. Conclusions The lockdown associated with COVID-19 has largely had a negative impact on the lifestyles of individuals and communities across many countries and cultures. However, some individuals and communities also initiated positive lifestyle-related behavioral changes. If the knowledge generated by studying the impact of COVID-19-related lockdowns on the six lifestyle factors is further consolidated, it could improve chronic disease outcomes. This will help better understand lifestyle behaviors amidst crises and assist in redesigning extreme public health measures such as lockdowns.. It is up to governments, communities, and healthcare/academic entities to derive benefit from lessons learned from the pandemic, with the ultimate objective of better educating and promoting healthy lifestyles among communities.

The government of the United Arab Emirates (UAE) considers technology to be one of the main pillars of its vision for moving towards a knowledge-based society. Due to several factors such as globalisation, demand for information technology infrastructure and COVID-19 lockdowns, e-learning has become a popular method of delivery across higher education institutions in the UAE. In a first step, the authors of this article conducted a systematic review of existing literature (49 items published between 1999 and 2020). They found that the existing literature on online learning predominantly focuses on student-specific challenges, while there is still a dearth of published work covering faculty members' specific challenges in facilitating online learning in the UAE. The second part of this exploratory study drew on stakeholders' reflections of several years of designing and delivering online courses, analysing faculty members' perspectives on online teaching and learning in the UAE. The authors present their qualitative research, which involved open-ended semi-structured interviews with 15 faculty members, followed by a thematic analysis of their responses using NVivo 12 pro software. The most critical themes which emerged were learners' expectations, culture, perception, pedagogy and technology. The article also reveals how these topics contribute to the various strategies for seamless adoption and delivery of online education in the UAE.

This project aimed to increase same-day emergency care (SDEC)-suitable activity within an existing ambulatory medical unit, in line with the recommendations set out in the NHS Long Term Plan. Prior to the project, much of the unit's activity was non-urgent and focused on supporting early discharges. Scoping exercises were undertaken to better understand current activity and identify interventions to increasing same-day referrals from within the urgent and emergency care system. Quality improvement methodology was then used to implement and study a variety of interventions, including but not limited to the development of new condition-based referral pathways. Retrospective review of SDEC activity demonstrated a threefold increase.

Background The primary objective worldwide during the coronavirus disease 2019 (COVID-19) pandemic had been controlling disease transmission. However, lockdown measures used to mitigate transmission affected human behavior and altered lifestyles, with a likely impact on chronic non-communicable diseases. More than a year into the pandemic, substantial peer-reviewed literature emerged on altered lifestyles following the varying lockdown measures imposed globally to control the virus spread. We explored the impact of lockdown measures on six lifestyle factors, namely diet, physical activity, sleep, stress, social connectedness, and the use of tobacco, alcohol, or other harmful substances. Methods We comprehensively searched PubMed and the World Health Organization’s global literature database on COVID-19 and retrieved 649 relevant articles for the narrative review. A critical interpretative synthesis of the articles was performed. Results Most of the articles included in the review identified the negative effect of lockdown measures on each of the lifestyle factors in many parts of the world. Encouraging lifestyle trends were also highlighted in a few articles. Such trends can positively influence the outcome of lifestyle-related chronic diseases, such as obesity and diabetes. Conclusions The lockdown associated with COVID-19 has largely had a negative impact on the lifestyles of individuals and communities across many countries and cultures. However, some individuals and communities also initiated positive lifestyle-related behavioral changes. If the knowledge generated by studying the impact of COVID-19-related lockdowns on the six lifestyle factors is further consolidated, it could improve chronic disease outcomes. This will help better understand lifestyle behaviors amidst crises and assist in redesigning extreme public health measures such as lockdowns.. It is up to governments, communities, and healthcare/academic entities to derive benefit from lessons learned from the pandemic, with the ultimate objective of better educating and promoting healthy lifestyles among communities.

Increased MMP-9 expression in the tumor microenvironment (TME) plays a crucial role in the extracellular matrix remodeling to facilitate cancer invasion and metastasis. However, the mechanism of MMP-9 upregulation in TME remains elusive. Since TGF-β and TNF-α levels are elevated in TME, we asked whether these two agents interacted to induce/augment MMP-9 expression. Using a well-established MDA-MB-231 breast cancer model, we found that the synergy between TGF-β and TNF-α led to MMP-9 upregulation at the transcriptional and translational levels, compared to treatments with each agent alone. Our in vitro findings are corroborated by co-expression of elevated MMP-9 with TGF-β and TNF-α in human breast cancer tissues. Mechanistically, we found that the MMP-9 upregulation driven by TGF-β/TNF-α cooperativity was attenuated by selective inhibition of the TGF-βRI/Smad3 pathway. Comparable outcomes were observed upon inhibition of TGF-β-induced phosphorylation of Smad2/3 and p38. As expected, the cells defective in Smad2/3 or p38-mediated signaling did not exhibit this synergistic induction of MMP-9. Importantly, the inhibition of histone methylation but not acetylation dampened the synergistic MMP-9 expression. Histone modification profiling further identified the H3K36me2 as an epigenetic regulatory mark of this synergy. Moreover, TGF-β/TNF-α co-stimulation led to increased levels of the transcriptionally permissive dimethylation mark at H3K36 in the MMP-9 promoter. Comparable outcomes were noted in cells deficient in NSD2 histone methyltransferase. In conclusion, our findings support a cooperativity model in which TGF-β could amplify the TNF-α-mediated MMP-9 production via chromatin remodeling and facilitate breast cancer invasion and metastasis.

BackgroundCoronavirus disease 2019 (COVID-19) caused by the coronavirus SARS-CoV-2, has emerged as a rapidly spreading contagious disease across the globe. Recent studies showed that people with diabetes mellitus, severe obesity, and cardiovascular disease are at higher risk of mortality from COVID-19. It has been suggested that the increased risk is due to the chronic inflammatory state associated with type 2 diabetes. This study aimed to evaluate the efficacy of pioglitazone, a strong insulin sensitizer with anti-inflammatory properties, in improving the clinical outcomes of patients with type 2 diabetes admitted with moderate–severe COVID-19.MethodWe enrolled 350 patients with type 2 diabetes who were admitted to hospitals in Qatar and Kuwait with COVID-19. Patients were randomized to receive, in a double-blind fashion, pioglitazone (n = 189) or a matching placebo (n = 161) for 28 days. The study had two primary outcomes: (1) the incidence of a composite outcome composed of (a) the requirement for mechanical ventilation, (b) death, and (c) myocardial damage; and (2) an increase in C-reactive protein (CRP) levels.ResultsThe first primary outcome occurred in 28 participants (8%), and the secondary outcome occurred in 17. Treatment with pioglitazone showed a significant reduction in interleukin (IL)-3 levels compared with placebo treatment (mean (SD) 2.73 (± 2.14) [95% CI: 0.02, 1.1], p = 0.043 vs. 2.28 (± 1.67) [95% CI: − 0.23, 0.86], p = 0.3, respectively), with no effect seen in the levels of other inflammatory markers. Even though not significant, a few of the patients on pioglitazone exhibited serum troponin levels > 3 times higher than the normal range seen in patients on placebo. On the other hand, more patients on pioglitazone were admitted to the ICU than those with placebo, and no significant difference in the CRP reduction was observed between the two groups.ConclusionThe results of the present study demonstrate that pioglitazone treatment did not independently provide any additional clinical benefit to patients with type 2 diabetes admitted with a COVID-19 infection.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT04604223.

Non-steroidal anti-inflammatory drugs like paracetamol, which have strong antibacterial and analgesic properties, are frequently employed in medicine. On the other hand, fulminant liver necrosis and other adverse reactions can result from paracetamol exposure. The development of useful analytical techniques is therefore necessary to identify and quantify paracetamol. Green determination techniques have been thoroughly studied in the last few years because of their simplicity, increased sensitivity and selectivity, and cost-effectiveness. The development of determination methods for quantification the presence of paracetamol in drugs and biological products has advanced, as this review details. The advancement in techniques for the selective detection of paracetamol during the past years was studied. In particular, the emphasis is on the inventive aspects brought about by spectrophotometry, chromatography, and automated devices. There is a lot of reviews on this topic, but no one has assessed the greenness of paracetamol determination approaches in biological samples. The two greenness scales were utilized for calculating the results. Analytical GREEnness Calculator (AGREE) and Complementary Green Analytical Procedure Index (ComplexGAPI) are simple, free, and sensitive programs.

Introduction In Kuwait, a severe diabetes and obesity epidemic coexists with intense dust storms and harsh summer heat. While, theoretically, this interplay between dust, heat, and diabetes presents a serious public health problem, the empirical understanding of the actual risks remains limited. We hypothesized that increased exposure to heat and dust, independently and jointly, exacerbates the risk of hospitalization for diabetes patients.Research design and methods We placed custom-designed particle samplers in Kuwait to collect daily dust samples for 2 years from 2017 to 2019. Samples were analyzed for elemental concentrations to identify and quantify dust pollution days. Temperature data were collected from meteorological stations. We then collected hospitalization data for unplanned diabetic admissions in all public hospitals in Kuwait. We used a case-crossover study design and conditional quasi-Poisson models to compare hospitalization days to control days within the same subject. Finally, we fitted generalized additive models to explore the smoothed interaction between temperature and dust days on diabetes hospitalization.Results There were 11 155 unplanned diabetes hospitalizations over the study period. We found that each year, there was an excess of 282 diabetic admissions attributed to hot days (95% CI: −14 to 473). Additionally, for every 10 µg/m3 increase in dust levels, there were about 114 excess diabetic admissions annually (95% CI: 11 to 219). Compared with mild non-dusty days (33°C (0 µg/m3)), hot–dusty days jointly increased the relative risk of diabetic admissions from 1.11 at 42°C (85 µg/m3) to 1.36 at 42°C (150 µg/m3).Conclusions Both heat and dust seem to contribute to the increased diabetes morbidity, with combined hot–dusty conditions exacerbating these risks even further.

BackgroundBreast cancer (BC) affects racial and ethnic groups differently, leading to disparities in clinical presentation and outcomes. It is unclear how Hispanic ethnicity affects BC outcomes based on geographic location and proximity to the United States (U.S.)/Mexico border. We hypothesized that the impact of race/ethnicity on BC outcomes depends on geographic location and country of origin within each BC subtype.MethodsWe analyzed BC data from the Texas Cancer Registry by race/ethnicity/birthplace according to BC subtype (luminal A/luminal B/human epidermal growth factor receptor 2 [HER2]/triple-negative breast cancer[TNBC]). Other covariates included age, geographic location (U.S., Mexico), residency (border, non-border), treatments, and comorbidities. Crude and adjusted effects of race/ethnicity and birthplace on overall survival (OS) were analyzed using Cox regression methods.ResultsOur analysis of 76,310 patient records with specific BC subtypes revealed that Hispanic and non-Hispanic Black (NHB) patients were diagnosed at a younger age compared with non-Hispanic White (NHW) patients for all BC subtypes. For the 19,748 BC patients with complete data on race/ethnicity/birthplace/residency, Hispanic patients had a higher mortality risk in the Luminal A subtype, regardless of birthplace, whereas U.S.-born Hispanics had a higher risk of death in the TNBC subtype. In contrast, NHB patients had a higher mortality risk in the Luminal A and HER2 subtypes. Residence along the U.S./Mexico border had little impact on OS, with better outcomes in Luminal A patients and worse outcomes in Luminal B patients aged 60–74 years.ConclusionRace/ethnicity, geographic birth location, and residency were significant predictors of survival in BC. Migration, acculturation, and reduced healthcare access may contribute to outcome differences.

The aryl hydrocarbon receptor (AhR) is a versatile environmental sensor and transcription factor found throughout the body, responding to a wide range of small molecules originating from the environment, our diets, host microbiomes, and internal metabolic processes. Increasing evidence highlights AhR’s role as a critical regulator of numerous biological functions, such as cellular differentiation, immune response, metabolism, and even tumor formation. Typically located in the cytoplasm, AhR moves to the nucleus upon activation by an agonist where it partners with either the aryl hydrocarbon receptor nuclear translocator (ARNT) or hypoxia-inducible factor 1β (HIF-1β). This complex then interacts with xenobiotic response elements (XREs) to control the expression of key genes. AhR is notably present in various crucial immune cells, and recent research underscores its significant impact on both innate and adaptive immunity. This review delves into the latest insights on AhR’s structure, activating ligands, and its multifaceted roles. We explore the sophisticated molecular pathways through which AhR influences immune and lymphoid cells, emphasizing its emerging importance in managing inflammatory diseases. Furthermore, we discuss the exciting potential of developing targeted therapies that modulate AhR activity, opening new avenues for medical intervention in immune-related conditions.

Polysaccharide-based packaging and its ever-increasing applications in response to the need for sustainable and safe packaging have prompted researchers to investigate the development of antimicrobial biopolymer-based packaging for shelf-life enhancement of food samples. A film made by blending chitosan and pectin had good mechanical properties, that is, a tensile strength of 7.43 MPa and an elongation at break of 23.033%. To produce active packaging, thyme essential oil (TEO) was added to the blend at concentrations of 10%, 15%, and 20%. The developed film was characterized for its techno-functional and antimicrobial properties. Further the developed films were employed in an active food packaging system for milk cake. Films with added TEO showed significant enhancements in elongation at break (28.22%) and water vapor barrier properties (30.08 g/h.m2). Additionally, the microstructure of the film was also improved, as demonstrated by scanning electron microscopy (SEM) and atomic force microscopy (AFM) measurements. Fourier transform infrared spectroscopy (FTIR) indicated the interaction of blended matrix (chitosan and pectin) and TEO as observed from the formation of hydrogen bonds with the addition of TEO owing to the OH functional groups. The use of TEO in pectin and chitosan-based film and its application for milk cake packaging showed delayed microbiological contamination and hardness of milk cake samples. The shelf life of milk cake packaged in pectin and chitosan blend film with 20% TEO was enhanced by > 10 days.

High-fat diets (HFDs) shape the gut microbiome and promote obesity, inflammation, and liver steatosis. Fish and soybean are part of a healthy diet; however, the impact of these fats, in the absence of sucrose, on gut microbial dysbiosis and its association with liver steatosis remains unclear. Here, we investigated the effect of sucrose-free soybean oil-and fish oil-based high fat diets (HFDs) (SF-Soy-HFD and SF-Fish-HFD, respectively) on gut dysbiosis, obesity, steatosis, hepatic inflammation, and insulin resistance. C57BL/6 mice were fed these HFDs for 24 weeks. Both diets had comparable effects on liver and total body weights. But 16S-rRNA sequencing of the gut content revealed induction of gut dysbiosis at different taxonomic levels. The microbial communities were clearly separated, showing differential dysbiosis between the two HFDs. Compared with the SF-Fish-HFD control group, the SF-Soy-HFD group had an increased abundance of Bacteroidetes, Firmicutes, and Deferribacteres, but a lower abundance of Verrucomicrobia. The Clostridia/Bacteroidia (C/B) ratio was higher in the SF-Soy-HFD group (3.11) than in the SF-Fish-HFD group (2.5). Conversely, the Verrucomicrobiacae/S24_7 (also known as Muribaculaceae family) ratio was lower in the SF-Soy-HFD group (0.02) than that in the SF-Fish-HFD group (0.75). The SF-Soy-HFD group had a positive association with S24_7, Clostridiales, Allobaculum, Coriobacteriaceae, Adlercreutzia, Christensenellaceae, Lactococcus, and Oscillospira, but was related to a lower abundance of Akkermansia, which maintains gut barrier integrity. The gut microbiota in the SF-Soy-HFD group had predicted associations with host genes related to fatty liver and inflammatory pathways. Mice fed the SF-Soy-HFD developed liver steatosis and showed increased transcript levels of genes associated with de novo lipogenesis (Acaca, Fasn, Scd1, Elovl6) and cholesterol synthesis (Hmgcr) pathways compared to those in the SF-Fish-HFD-group. No differences were observed in the expression of fat uptake genes (Cd36 and Fabp1). The expression of the fat efflux gene (Mttp) was reduced in the SF-Soy-HFD group. Moreover, hepatic inflammation markers (Tnfa and Il1b) were notably expressed in SF-Soy-HFD-fed mice. In conclusion, SF-Soy-HFD feeding induced gut dysbiosis in mice, leading to steatosis, hepatic inflammation, and impaired glucose homeostasis.