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Reactivity of aragonite with dicalcium phosphate facilitates removal of dental calculus.
No full textDental calculus, a main contributor of periodontal diseases, is mostly composed of inorganic calcium phosphate species such as dicalcium phosphate, whitlockite, octa calcium phosphate, and hydroxyapatite. Under physiological pH 7.4, dicalcium phosphates can gradually interact with calcium carbonate to form hydroxyapatite. Therefore, we hypothesized that aragonite (Arg) could react with dental calculus, facilitating its removal. To assess the reactivity of Arg with dental calculus, we examined the changes in surface morphology, composition, and topography of Arg and dental calculus upon exposure to each other in an aqueous environment. The impact of Arg on the removal of dental calculus was assessed by brushing polished sections of dental calculus, enamel, and dentin with slurries of Arg and measuring the depth of abrasion using a stylus profilometer. Our results demonstrate that Arg can react with dental calculus in aqueous environment. This reaction increases calculus surface roughness which in turn facilitate dental calculus removal by brushing. Aragonite could be a promising abrasive for toothpaste design for management of dental calculus.Open Access funding provided by the Qatar National Library
Neratinib and metformin: A novel therapeutic approach against HER2-Positive Breast Cancer
No full textBackgroundHER2-positive breast cancer (BC) is highly aggressive with a poor prognosis. It is driven by HER2 oncoprotein activation/crosstalk with other receptors like EGFR/(HER1), HER3, and HER4, in addition to IGF-1R, making these receptors ideal therapeutic targets as they are expressed/overexpressed in this subtype. We postulated that targeting HER2 and IGF-1R together is a promising therapy for HER2-positive BC. Thus, we explored the outcome of a novel combination treatment using neratinib, a pan-HER inhibitor, and metformin, an IGF-1R inhibitor, on HER2-positive BC cells. Methods: In this investigation, we used cellular and molecular biology techniques in addition to an angiogenesis model and tissue microarray analysis. Results: Our data revealed that this combination therapy significantly reduced cell viability compared to individual treatments and exhibited a synergistic effect in HER2-positive BC cells. Moreover, the combination disrupted cell cycle progression and inhibited colony formation, and invasion of HER2-positive BC cells; this is accompanied by the deregulation of HER1–3 and IGF-1R expression patterns, in addition to Caspase-3, BCL2, Fascin, and Vimentin. Moreover, key regulator molecular pathways, including, ERK1/2, AKT, p38 MAPK, and mTOR, were significantly downregulated upon treatment with neratinib and metformin combination. Additionally, our data pointed out that neratinib and metformin combination inhibited angiogenesis, in-ovo, an important biological event in cancer progression. Finally, using a cohort of 55 HER2-positive BC samples, we revealed that HER2 and IGF-1R are co-expressed in most of the cases. Conclusions: These findings suggest that neratinib and metformin combination can present a promising strategy for targeting multiple pathways in HER2-positive BC.This work was funded by Qatar National Research Fund #ECRA03–003-3-002
The Economy of Formulation within Morphological Patterns: An Epistemological Study
No full textدرس البحث مفهوم اقتصاد الصياغة في (إبستمولوجيا) العِلْمِ وفي اللسانيات، وهو أحد خصائص العلم، وشروط بناء النظريات العلمية. وبين مدى توسع العلماء المعاصرين في تحليله واعتماده، سواءٌ أكان ذلك في صياغة النظريات أم المفاضلة بينها.
وقد نزّل البحث مبدأ الاقتصاد على الميزان الصرفي الذي صاغَهُ النحويون؛ لضبط أبنية العربية المشتقّةِ، وكَشَفَ عن مَدى التزامِ النحويين بتطبيقِ هذا المبدأ واعتباره أساسًا في بنائهم النظري، دون أَنْ يُصَرحوا به، وقد اتخذَ النحويون وسائِلَ نظرية مُتَعددةً لِتَقلِيلِ الأوزانِ الصرفية والمحافظةِ على بساطة الصياغة؛ كالتجريد، والرد إلى الأصل النظري، وغيرهما؛ في حين نقد بعضُ الباحثين الوصفيين الأصولَ النظرية التي حقّق بها النحويون اقتصادَ الصياغة. وقد اعتمدَ البحثُ في معالجةِ هذه القضية المنهجَ الوصفي التحليلي.This study examines the concept of Economy of Formulation within the epistemology of science and linguistics, identifying it as a key feature of rigorous science and a prerequisite for the construction of scientific theories. The research highlights the extent to which contemporary scholars have expanded their analysis and application of this principle, both in the formulation of theories and in choosing between competing theories.The study applies the principle of economy to the morphological pattern developed by classical Arabic grammarians to regulate derived structures in the Arabic language. It reveals the extent of their adherence to this principle and its implicit role in their theoretical frameworks, even without explicit acknowledgment. Grammarians employed various theoretical tools to reduce morphological patterns and maintain simplicity in formulation, such as abstraction and reduction to the root form. Meanwhile, some descriptive scholars have critiqued the theoretical foundations upon which these grammarians based their economy of formulation. The study employs a descriptive-analytical methodology to address this issue
Pharmacological strategies to bridge the gap between cancer and cardiovascular therapeutics
No full textThroughout the history of biomedical research, few endeavors have proven as formidable as the quest to defeat or overcome cancer and cardiovascular diseases (CVDs). Indeed, these twin scourges continue to distress humanity with unrelenting ferocity. In Pharmacological Reviews, Avolio et al (2024) tease the shared molecular, cellular, and environmental hallmarks between these two seemingly disparate conditions. The authors offer a rather tempting glimpse into the potential for drug repurposing as a means to combat both maladies simultaneously. Cancer and CVD are not merely distinct entities. Rather, they are intricately intertwined through common biological pathways. The authors rigorously examined the intricate web of signaling and cellular mechanisms that underlie both conditions. They also discussed how chronic inflammation, immune dysregulation, and pathological tissue remodeling are common threads that weave through both conditions. Avolio et al (2024) meticulously dissected these shared mechanisms and shed light on their role in driving disease progression in both cancer and CVD. This comprehensive analysis highlights various avenues for therapeutic intervention made possible by this newfound understanding. The authors examined the concept of drug repurposing because it applies to this cardio-oncology frontier. This strategy of drug repositioning is predicted to accelerate the development of novel treatments for CVD by leveraging the vast arsenal of anticancer therapeutics already at our disposal. Though not without its challenges, this prospect offers a tantalizing shortcut to the traditionally protracted and costly process of drug discovery and development. The authors emphasized that many anticancer drugs do indeed target pathways relevant to both diseases. They followed that by suggesting that a reevaluation of these agents would therefore be only expected to yield significant benefits for patients with CVDs. This approach has indeed excited clinicians and researchers alike, offering hope for more expeditious interventions in the face of urgent medical needs. The article addresses the pharmacological facets of drug repurposing with commendable depth. The authors underscore key signaling pathwaysdsuch as extracellular signal-regulated kinase ½, signal transducer and activator of transcription 3, transforming growth factor b; neurogenic locus notch homolog protein, and Myc proto-oncogene proteindthat are involved in both cancer and CVD. By pinpointing these pathways as potential targets, they provide a roadmap for future research endeavors aimed at develo** dualpurpose therapies. This emphasis on shared mechanisms not only deepens our grasp of disease biology but also lays the foundation for innovative treatment paradigms that transcend traditional disciplinary boundaries
ASSESSING THE OUTCOMES AND EFFECTIVENESS OF THE NATIONAL PREMARITAL GENETIC SCREENING PROGRAM IN QATAR
No full textBackground: Premarital screening (PMS) programs have been increasingly implemented in various countries due to their potential to reduce the incidence of genetic diseases. In Qatar, a PMS program has been in place since 2009 as a mandatory prerequisite for marriage. Since then, its outcomes have not been explored. Aim: To assess the outcomes and effectiveness of Qatar's PMS program. To identify potential gaps in its implementation and provide insights to guide improvements. Methods: A retrospective population-based study on the PMS testing results for the conditions cystic fibrosis (CF), homocystinuria (HCU) and spinal muscular atrophy (SMA) from 2009 to 2023. Results: A total of 75,767 tests were initiated within this period with 99% of samples belonging to nationals. Testing for CF (47%) and HCU (48%) was similarly high compared to SMA which was lower (5%), consistent with its optional screening status. The most common age at marriage was 20-30 years for females and 31-40 years for males. Our study sample included 50908 individuals. Carrier rates were highest for SMA (4.47%), followed by HCU (2.06%) and CF (1.46%). Among all carriers, HCU was the most common (n=498), followed by CF (n=349) and SMA (n=126). Among at-risk couples, 43.5% were positive for SMA, 30.5% for HCU, and 25.9% for CF. Consanguinity was reported in 46% of positive couples (where data was available) and was significantly associated with a higher likelihood of positive results (p < 0.001). More than half (53.6%) of at-risk couples continued with marriage. Among those, 92% did not have affected children. Use of reproductive assistance with genetic testing was observed in 12.6% of positive couples, while 7.5% did not utilize it. Importantly, use of such technology was significantly associated with a reduced incidence of affected children. Conclusion: Qatar's PMS program was effective in reaching its end-goal which is reducing the incidence of the specified conditions. However, the absence of affected children among at-risk couples may be influenced by various factors, including chance, infertility, or pregnancies with yet unknown outcomes. Therefore, while the results are encouraging, they should be interpreted with caution. Our findings demonstrate the success of the program approach but highlights the need for enhanced risk counseling after positive results, and the need for public educational campaigns highlighting the importance of premarital testing and the potential risks associated with consanguinity
Longitudinal exploration of the educational identity formation through a Graduate Certificate in Health Professions Education
No full textBackground: Previous studies reported the impact retrospectively, making it difficult to tease out the influence of the Graduate Certificate in Health Professions Education (CHPE) from other development activities and experiences. This study extends the inquiry through the longitudinal follow-up of the participants while engaging with the program and beyond, through reflections on their educational identity. The study explores the motivations for enrolling, the impact on careers, and educational identity formation throughout a CHPE program and afterwards. Methods: Qualitative Longitudinal Research underpinned by communities of practice theory was conducted. A purposive sample of 32 health professionals enrolled for CHPE were asked to record reflective audio diaries documenting any significant events during the program that may have impacted their beliefs as educators. 12 participants were also interviewed six months after the program. A thematic framework analysis was conducted. Results: Participants enrolled for various intrinsic and extrinsic motivations and developed an interest over time. They learned the theoretical basis of their educational practices, with increasing self-efficacy and transformational changes as teachers, leaders, and researchers. They also reported having additional educational responsibilities and a competitive advantage in promotions at their institution. Participants also initiated curriculum reforms in the workplace. Participants reported professional inclusiveness with a sense of belongingness in the educational communities of practice. Many also enrolled for a Masters in Health Professions Education. Conclusion: This is the first qualitative longitudinal study exploring the impact of a CHPE program on health professionals from various specialties and workplaces while engaging with the program and beyond. Through the course, health professionals develop an interest in education with increasing self-efficacy. The program results in transformational changes and educational identity formation as teachers, leaders, and researchers. The graduates also get educational responsibilities and promotions. Those enrolled experience professional inclusiveness and a sense of belongingness with the educational communities.This work was supported by AMEE for the FDP Grant
Appointment of Dr. Mohammed Al-Safran as the new Assistant Vice President (AVP) for Research and Graduate Studies at Qatar University = تعيين الدكتور محمد السفران مساعدًا لنائب رئيس الجامعة للبحث والدراسات العليا
No full textتعيين الدكتور محمد السفران مساعدًا لنائب رئيس الجامعة للبحث والدراسات العليا
Trends in the global, regional, and national burden of oral conditions from 1990 to 2021: a systematic analysis for the Global Burden of Disease Study 2021
No full textBackgroundThe WHO Global Oral Health Action Plan has set an overarching global target of achieving a 10% reduction in the prevalence of oral conditions by 2030. Robust and up-to-date information on the global burden of oral conditions is paramount to monitor progress towards this target. The aim of this systematic data analysis was to produce global, WHO region, and country-level estimates of the prevalence of, and disability-adjusted life-years (DALYs) attributed to, untreated caries, severe periodontitis, edentulism, other oral disorders, lip and oral cavity cancer, and orofacial clefts from 1990 to 2021. MethodsThis report is based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. Input data were extracted from epidemiological surveys, population-based registries, and vital statistics. Data were modelled with DisMod-MR 2.1, a Bayesian meta-regression modelling tool, to ensure consistency between prevalence, incidence, remission, and mortality estimates for oral conditions. DALYs were estimated as the aggregation of the years of life lost (YLLs) due to premature mortality and years lived with disability (YLDs). YLDs were calculated by multiplying prevalence estimates, the severity of the oral condition's sequelae (disability weight) and duration of the sequelae. Although all oral conditions lead to YLDs, only lip and oral cavity cancer and orofacial clefts lead to YLLs as well. 95% uncertainty intervals (UIs) were generated for every metric with the 25th and 975th ordered 1000 draw values of the posterior distribution. FindingsThe combined global age-standardised prevalence of the main oral conditions (untreated caries, severe periodontitis, edentulism, and other oral disorders) was 45 900 (95% UI 42 300 to 49 800) per 100 000 population in 2021, with 3·69 billion (3·40 to 4·00) people affected globally. Untreated dental caries of permanent teeth and severe periodontitis were the most common oral conditions, with a global age-standardised prevalence of 27 500 (24 000 to 32 000) per 100 000 population and 12 500 (10 500 to 14 500) per 100 000 population, respectively. Edentulism, severe periodontitis, and lip and oral cavity cancer caused the highest burden as demonstrated by their counts of DALYs and age-standardised DALY rates. Existing trends for 1990–2021 reveal relatively small changes (upward or downward) in prevalence and burden. Increasing counts of prevalent cases and DALYs were noted for all oral conditions but untreated caries of deciduous teeth (no percentage change in prevalence or DALYs) and orofacial clefts (–68·3% [–79·3 to –46·5] decrease in DALYs). There were decreases in both age-standardised prevalence and DALY rate for untreated caries of permanent teeth and edentulism, no change in both for untreated caries of deciduous teeth and severe periodontitis, an increase in the prevalence but no change in the DALY rate for lip and oral cavity cancer, and no change in the prevalence but a decrease in the DALY rate for orofacial clefts. By WHO region, the African and Eastern Mediterranean regions showed the largest increases in prevalent cases and DALYs for most oral conditions, while the European region showed the smallest increases or no change. The European region was the only region with decreasing age-standardised prevalence of untreated caries in both deciduous (–9·88%; –12·6 to –6·71) and permanent teeth (–5·94% (–8·38 to –3·62). The prevalence and DALY rate of severe periodontitis decreased in the African region, while the prevalence and DALY rate of edentulism decreased in the African region, South-East Asia region, and Western Pacific region. Furthermore, DALY rates of lip and oral cavity cancer decreased in the European region and the region of the Americas, while DALY rates of orofacial clefts decreased in all regions. InterpretationThe minor changes in the burden of oral conditions over the past 30 years demonstrate that past and current efforts to control oral conditions have not been successful and that different approaches are needed. Many countries now face the double challenge of controlling the occurrence of new cases of oral conditions and addressing the huge unmet need for oral health care. FundingBill & Melinda Gates Foundation
Reported Postoperative Surgical Site Infections in Tertiary Care Hospitals, Systematic Review of Recent Literature.
No full textThe objective of this systematic review is to evaluate the patterns of postsurgical site infections, pre-surgical antibiotics prophylaxis, and related clinical outcomes in the recently published literature. This systematic review is registered with PROSPERO registration number CRD42023398963. Several databases and individual journal websites were used to collect data from PubMed/Medline, TRIP, SCOPUS, Elsevier, Springer, ProQuest, and EMBASE. The established criteria of inclusion were RCTs, retrospective, prospective, and cross-sectional studies with patients who had a recent surgical procedure. Excluded from the study designs were systematic reviews, prospective studies, data on pediatrics, and data on disabilities. Quality assessment analysis of the results for randomized controlled trials (RCT) used CONSORT guidelines and STROBE guidelines for cross-sectional and cohort studies. A total of 328 articles were identified from different databases. Among them, 15 studies were included for data extraction and qualitative analysis. A total of 33,193 patients with an average rate of 11.5% (surgical site infections- SSIs) were identified in these studies during 2008-2022. The mean rate of SSIs among the total number of immunocompromised patients/procedures was 10.2%. The SSI on patients undergoing major surgical procedures with visible incisions was 26.0%. The majority of the studies reported the use of pre-surgical antibiotic prophylaxis. Cefazolin was mostly prescribed antibiotics and administered in 90% of patients. Other antibiotics included ceftriaxone (4%), cloxacillin (3%), and vancomycin (4%). The mean reported rate of SSIs with combination antibiotic prophylaxis therapy was 22.8%. This systematic review concluded the limited reported data on surgical site infections (SSIs). The overuse of pre-surgical antibiotic prophylaxis has been reported in several studies. This study recommended developing standardized guidelines on the use of antibiotics related to surgical cases rather than co-morbidities
Predicting the likelihood of carrying BRCA1 or BRCA2 pathogenic variants in high-risk Pakistani breast cancer patients
No full textPurpose: Pathogenic variants (PVs) in BRCA1/2 increase the lifetime risk of breast cancer (BC). Predictive algorithms for BRCA1/2 PVs, primarily developed for Caucasian BC patients, often underestimate carrier probability in Asian populations. The recently developed Asian Risk Calculator (ARiCa) aims to predict BRCA1/2 PV likelihood in Malaysian/Singaporean BC patients. This study investigates the ARiCa’s performance in Pakistani female BC patients. Methods: A cohort of 627 high-risk Pakistani female BC patients was evaluated. Using ARiCa, the likelihood of being a BRCA1/2 carrier was estimated based on factors such as age at diagnosis, ethnicity, bilateral BC status, tumor histopathological features, and family history of BC or ovarian cancer. The tool’s discriminative ability was evaluated using the area under the curve (AUC). Results: Of the participants, 133 (21.2%) were BRCA1 carriers, 25 (4.0%) were BRCA2 carriers, and 469 (74.8%) were non-carriers. The mean age at BC diagnosis was 34.3 years (range 19–73). Overall, ARiCa showed well calibration for predicting BRCA1/2 (HL 12.11, P = 0.147), BRCA1 (HL 14.17, P = 0.078), and BRCA2 carriers (HL 9.01, P = 0.342). The tool showed acceptable discrimination for BRCA1/2 (AUC 0.77, 95% CI 0.72–0.81) and BRCA1 carriers (AUC 0.80, 95% CI 0.75–0.84), but lower discrimination for BRCA2 carriers (AUC 0.51, 95% CI 0.39–0.64). At a 21% threshold, ARiCa would recommend BRCA1/2 screening for 43% of patients, with sensitivity and specificity at 73% and 68%, respectively. Conclusion: The ARiCa tool demonstrates strong predictive performance for BRCA1/2 carriers, specifically for BRCA1 carriers in Pakistani BC patients, suggesting its potential clinical utility.This work was supportd by Soo Hwang Teo (ARiCa tool\u2019s). It was also funded by the institutional support from Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan (Grant # ONC-BRCA-002)