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EMPOWERING PRECISION MEDICINE: MAPPING METASTATIC POTENTIAL THROUGH DEPIS-ENABLED MICROCHIP FOR CANCER CELL CAPTURE AND ANALYSIS
No full textMetastasis, the leading cause of cancer-related deaths, is the spread of cancer to other body regions. This process is characterized by the migration of tumor cells, known as circulating tumor cells (CTCs), into distant regions of the body during the disease progression. The number of CTCs is relatively low (order of 1 cell/mL), but their detection might hold potential in cancer diagnostics, prognostics, and targeted therapeutics, through CTC characterization. However, current detection methods result in high false negative rates due to their dependency on cell surface-markers expression rendering a major population of CTCs undetected. In addition, these methods are expensive and do not allow post-capture cell analysis. Label-free methods, an alternative to detect CTCs, have emerged and defied these drawbacks by relying on the physical characteristics of the cells such as shape, size, deformability, density, and surface charge. Dielectrophoresis (DEP) is a developing application of label-free platforms for CTC detection that uses non-uniform electric fields to induce particle motion and manipulation to separate and differentiate CTCs from multiple origins in the same sample. In this project, we developed a bimodal DEP-based platform for the DEP-based trapping and EIS-based detection and electrical characterization of three MDA-MB-231 breast cancer cells subtypes using inkjet technology to print an array of silver electrodes. Our results show that our platform is capable of trapping and separating populations of cells with high sensitivity, specificity, and enumerating and differentiating populations based on their cell count and internal physiology
Vaccine evaluation and genotype characterization in children infected with rotavirus in Qatar
No full textBackground: We characterized and identified the genetic and antigenic variations of circulating rotavirus strains in comparison to used rotavirus vaccines. Methods: Rotavirus-positive samples (n = 231) were collected and analyzed. The VP7 and VP4 genes were sequenced and analyzed against the rotavirus vaccine strains. Antigenic variations were illustrated on the three-dimensional models of surface proteins. Results: In all, 59.7% of the hospitalized children were vaccinated, of which only 57.2% received two doses. There were no significant differences between the vaccinated and non-vaccinated groups in terms of clinical outcome. The G3 was the dominant genotype (40%) regardless of vaccination status. Several amino acid changes were identified in the VP7 and VP4 antigenic epitopes compared to the licensed vaccines. The highest variability was seen in the G3 (6 substitutions) and P[4] (11 substitutions) genotypes in comparison to RotaTeq®. In comparison to Rotarix®, G1 strains possessed three amino acid changes in 7-1a and 7-2 epitopes while P[8] strains possessed five amino acid changes in 8-1 and 8-3 epitopes. Conclusions: The current use of Rotarix® vaccine might not be effective in preventing the infection due to the higher numbers of G3-associated cases. The wide range of mutations in the antigenic epitopes compared to vaccine strains may compromise the vaccine’s effectiveness. Impact: The reduced rotavirus vaccine effectiveness necessitate regular evaluation of the vaccine content to ensure optimal protection.We characterized and identified the genetic and antigenic variations of circulating rotavirus strains in comparison to the Rotarix vaccine strain that is used in Qatar.The study highlight the importance for regular monitoring of emerging rotavirus variants and their impact on vaccine effectiveness in young children. © 2023, The Author(s)
Utilization of patient portals: a cross-sectional study investigating associations with mobile app quality
No full textBackground: Mobile apps facilitate patients’ access to portals and interaction with their healthcare providers. The COVID-19 pandemic accelerated this trend globally, but little evidence exists on patient portal usage in the Middle East, where internet access and digital literacy are limited. Our study aimed to explore how users utilize a patient portal through its related mobile app (MyChart by EPIC). Methods: We conducted a cross-sectional survey of MyChart users, recruited from a tertiary care center in Lebanon. We collected MyChart usage patterns, perceived outcomes, and app quality, based on the Mobile Application Rating Scale (user version, uMARS), and sociodemographic factors. We examined associations between app usage, app quality, and sociodemographic factors using Pearson’s correlations, Chi-square, ANOVA, and t-tests. Results: 428 users completed the survey; they were primarily female (63%), aged 41.3 ± 15.6 years, with a higher education level (87%) and a relatively high crowding index of 1.4 ± 0.6. Most of the sample was in good and very good health (78%) and had no chronic illnesses (67%), and accessed the portal through MyChart once a month or less (76%). The most frequently used features were accessing health records (98%), scheduling appointments (67%), and messaging physicians (56%). According to uMARS completers (n = 200), the objective quality score was 3.8 ± 0.5, and the subjective quality was 3.6 ± 0.7. No significant association was found between overall app usage and the mobile app quality measured via uMARS. Moreover, app use frequency was negatively associated with education, socioeconomic status, and perceived health status. On the other hand, app use was positively related to having chronic conditions, the number of physician visits and subjective app quality. Conclusion: The patient portal usage was not associated with app quality but with some of the participants’ demographic factors. The app offers a user-friendly, good-quality interface to patient health records and physicians, appreciated chiefly by users with relatively low socioeconomic status and education. While this is encouraging, more research is needed to capture the usage patterns and perceptions of male patients and those with even lower education and socioeconomic status, to make patient portals more inclusive. © 2023, BioMed Central Ltd., part of Springer Nature
The hypertension cascade of care in the midst of conflict: the case of the Gaza Strip
No full textAlthough hypertension constitutes a substantial burden in conflict-affected areas, little is known about its prevalence, control, and management in Gaza. This study aims to estimate the prevalence and correlates of hypertension, its diagnosis and control among adults in Gaza. We conducted a representative, cross-sectional, anonymous, household survey of 4576 persons older than 40 years in Gaza in mid-2020. Data were collected through face-to-face interviews, anthropometric, and blood pressure measurements. Hypertension was defined in anyone with an average systolic blood pressure ≥140 mmHg or average diastolic blood pressure ≥90 mmHg from two consecutive readings or a hypertension diagnosis. The mean age of participants was 56.9 ± 10.5 years, 54.0% were female and 68.5% were Palestinian refugees. The prevalence of hypertension was 56.5%, of whom 71.5% had been diagnosed. Hypertension was significantly higher among older participants, refugees, ex-smokers, those who were overweight or obese, and had other co-morbidities including mental illnesses. Two-thirds (68.3%) of those with hypertension were on treatment with one in three (35.6%) having their hypertension controlled. Having controlled hypertension was significantly higher in females, those receiving all medications for high blood pressure and those who never or rarely added salt to food. Investing in comprehensive but cost-effective initiatives that strengthen the prevention, early detection and timely treatment of hypertension in conflict settings is critical. It is essential to better understand the underlying barriers behind the lack of control and develop multi-sectoral programs to address these barriers. © 2022, The Author(s)
Recovery course of persistent posterior subretinal fluid after successful repair of rhegmatogenous retinal detachment
No full textPurpose: To investigate best corrected visual acuity (BCVA), subretinal fluid (SRF) absorption time or ellipsoid zone (EZ) restoration time and various variables in patients with persistent SRF after successful primary repair of rhegmatogenous retinal detachment (RRD). Methods: This retrospective multicenter study allowed independent analysis of the healing pattern by two observers based on composite of serial cross-sectional macular optical coherence tomography (OCT) scans. Univariate and multivariate analyses were implemented. Results: One hundred and three cases had persistent SRF after pars plana vitrectomy, scleral buckling, or pneumatic retinopexy. By univariate analysis, SRF resolution time correlated positively with the number of retinal breaks (p < 0.001) and with increased myopia (p = 0.011). Using multivariate analysis, final BCVA (log MAR) correlated positively with age, duration of RRD, initial BCVA (OR = 3.28; [95%CI = 1.44–7.47]; p = 0.015), and SRF resolution time (OR = 0.46 [95%CI 0.21–1.05]; p = 0.049). EZ restoration time was longer with increasing number of retinal tears (OR = 0.67; [95%CI 0.29–1.52]; p = 0.030), worse final BCVA, and presence of macula-off RRD (OR = 0.26; [95%CI 0.08–0.88]; p = 0.056). SRF resolution time correlated marginally with prone position. Conclusions: Residual posterior SRF is more common in eyes with multiple breaks or in myopic eyes. Final BCVA is better in younger subjects and in eyes with shorter duration of RRD. Persistent SRF is a self-limited disorder with a mean resolution of 11.2 months with good visual prognosis improving from a mean baseline logMAR of 1.08 to 0.25 at one year. © The Author(s) 2023
Ethnopharmacology and therapeutic potential of Anchusa strigosa: a comprehensive review
Get PDFAnchusa strigosa Banks and Sol. is a rough flowering plant of the Boraginaceae family native to Eastern Mediterranean region that is widely used in traditional herbal medicine, mainly for the treatment of wounds, abdominal pain, and arthritis, to name a few. This article aims to gather knowledge related to the medicinal properties of A. strigosa. Specifically, it summarizes its traditional uses and pharmacological activities in the treatment of various diseases. Moreover, its botanical, ecological, and phytochemical characteristics are also discussed. Research showed that this plant is rich in pyrrolizidine alkaloids, particularly in the leaves. Other bioactive metabolites identified in this plant include flavonoids, phenolic acids, triterpenes, organic acids, and volatile organic compounds. These phytochemicals are responsible for the reported pharmacological properties of A. strigosa, including antimicrobial, antioxidant, anticancer, anti-inflammatory, antiarthritic, gastric protective, antidiabetic, and pro-wound healing. This warrants further investigation into the molecular mechanism of action behind the observed effects to elucidate its therapeutic potential. Nevertheless, more research on this plant is needed to ensure its efficacy and safety. Copyright © 2023 Chebaro, Badran, Maresca, Baydoun and Mesmar
Effect of Vitamin D Deficiency on Voice: A Review of the Literature
Get PDFObjective: The purpose of this study is to review the current literature on the effect of hypovitaminosis D on voice. Study design: Narrative review. Methods: The literature search from electronic databases included PubMed/MEDLINE, EMBASE, SCOPUS, and Google Scholar. Search terms included voice, voice quality, voice disorders, larynx, laryngology, acoustic analysis, vitamin D, calcitriol, cholecalciferol, vitamin D deficiency, and vitamin D insufficiency. All studies on patients with vitamin D deficiency, which included subjective and objective voice assessments, were reviewed. Results: A total of 39 studies were retrieved. Only four studies met the above-mentioned inclusion criteria and hence were included in this review. The total number of subjects analyzed was 466. The subjective voice outcome measures used were the Voice Handicap Index-10 (VHI-10), self-reported phonatory symptoms, and the GRBAS scale. Objective voice outcome measures included fundamental frequency, jitter, shimmer, noise-to-harmonic ratio, maximum phonation time, and dysphonia severity index. Conclusion: Vitamin D deficiency has no significant effect on laryngeal muscles. There was no statistically significant difference in VHI-10 score, self-reported dysphonia, perceptual voice evaluation scores, or any of the acoustic measures between those with or without vitamin D deficiency. © 2023 The Voice Foundatio
Gender based violence (GBV) coordination in a complex, multi-crisis context: a qualitative case study of Lebanon’s compounded crises (2019–2023)
Get PDFBackground: Since 2019 Lebanon has faced multiple compounded crises. Political and social instability, the COVID-19 pandemic, and the Beirut Port explosion, alongside the influx of refugees related to the ongoing Syrian conflict, have resulted in a nationwide economic emergency. In the context of the humanitarian response to the Syrian conflict, the UN and government-led gender-based violence (GBV) task force has coordinated the sub-sector since 2012. The compounded crisis, however, created new challenges for GBV coordination and service delivery, which we explore in this paper. We highlight lessons for strengthening GBV coordination in Lebanon and other complex emergencies. Methods: We conducted 29 remote in-depth interviews, reviewed key policy documents and observed seven GBV task force meetings. We analysed and presented our findings across three key themes: context-relevant and adaptable coordination mechanisms; coordination to support GBV service delivery; and stakeholders’ roles, legitimacy and power. Results: Parallel response frameworks developed to address the multiple crises, created a complex humanitarian architecture within an increasingly challenging operating context, with some perceived inefficiencies. Positively, coordination was integrated under the established government-UN interagency system and the GBV task force maintained GBV sub-sector coordination. The task force was commended for effectively adapting to the evolving context, including working remotely, maintaining essential GBV services, assessing the compounded crises’ impact on programming and adjusting accordingly, and harmonising guidance, tools and approaches. The importance of ensuring a government co-led response was highlighted by both UN and government informants, who pointed to examples where marginalising government leadership compromised coordination effectiveness and sustainability. The participation of local actors had become increasingly important but more difficult, with the impact of the various crises, and remote modalities, challenging service delivery and staff wellbeing. Conclusion: Experiences from Lebanon highlight the essential role of government leadership in coordination; the value of investing in local GBV capacity; the significance of effective national, subnational and intersectoral coordination to support service delivery and address cross-cutting GBV issues; the importance of targeted interventions to support marginalised populations; and the need to prioritize the well-being of front-line staff during crisis response. In Lebanon, and other complex crises, donors are encouraged to increase flexible, multiyear funding for GBV coordination and services, while women-led organizations should be at the forefront of recovery efforts, contributing to a more equitable society. © 2023, BioMed Central Ltd., part of Springer Nature
Studying the effect of partial drainage on the response of soft clays reinforced with sand column groups
No full textThe drained and undrained response of soft clays reinforced with granular columns has been the subject of numerous geotechnical research efforts to date. Although these studies have been essential for the development of design methodologies, the actual/true response of reinforced clay systems under realistic loading rates is likely governed by partially drained conditions that have yet to be investigated. Partial drainage occurs as a result of inevitable radial flow from the clay to the columns throughout the loading phase. Ignoring the positive effect of partial drainage on the short-term stability of foundations and/or embankments on a clay substratum reinforced with free draining columns may lead to over conservative designs. The objective of this study is to investigate the impact of partial drainage on the response of soft clays reinforced with sand column groups. To address this issue, four partially drained triaxial tests were conducted at different strain rates on normally consolidated soft clays reinforced with dense sand columns in a square configuration. Results included the effect of partial drainage on the total deviatoric stress, excess pore water pressure dissipation, volumetric strain, and stress concentration ratio. The results were bracketed between the fully drained and fully undrained responses/graphs that served as upper and lower bounds, respectively. A plot of the normalized improvement index vs tfailure/t50 showed full mobilization of strength at a time ratio of 15. Numerical modeling using finite difference of the pore water pressure dissipation during shearing was conducted. The consolidation results obtained from the numerical analyses were compared to measurements from the experimental program. The calculated degree of consolidation from the finite difference analysis correlated very well with the measured levels of consolidation during the tests. The results from the test program and the associated analyses presented in this paper contribute to enhancing our current understanding of the response of reinforced clay systems and may be a step on the road towards improving existing design methodologies. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature
The Antitumor Effect of the DNA Polymerase Alpha Inhibitor ST1926 in Glioblastoma: A Proteomics Approach
Get PDFGlioblastoma Multiforme (GBM) is the most aggressive form of malignant brain tumor. The median survival rate does not exceed two years, indicating an imminent need to develop novel therapies. The atypical adamantyl retinoid ST1926 induces apoptosis and growth inhibition in different cancer types. We have shown that ST1926 is an inhibitor of the catalytic subunit of DNA polymerase alpha (POLA1), which is involved in initiating DNA synthesis in eukaryotic cells. POLA1 levels are elevated in GBM versus normal brain tissues. Therefore, we studied the antitumor effects of ST1926 in several human GBM cell lines. We further explored the global protein expression profiles in GBM cell lines using liquid chromatography coupled with tandem mass spectrometry to identify new targets of ST1926. Low sub-micromolar concentrations of ST1926 potently decreased cell viability, induced cell damage and apoptosis, and reduced POLA1 protein levels in GBM cells. The proteomics profiles revealed 197 proteins significantly differentially altered upon ST1926 treatment of GBM cells involved in various cellular processes. We explored the differential gene and protein expression of significantly altered proteins in GBM compared to normal brain tissues. © 2023 by the authors