Characteristics, Outcomes, and Associations of Venous Thromboembolism in Diabetic Patients Infected With COVID-19 in Riyadh, Saudi Arabia.

Background The associations and risk factors for venous thromboembolism (VTE) among hospitalized COVID-19 patients remain ambiguous in the literature, with some conflicting findings, especially in Saudi Arabia. In this study, we aim to elaborate on these data by examining regional patient populations and exploring the incidence, lab findings, and outcomes of VTE among hospitalized COVID-19 patients known to have diabetes mellitus (DM). Methodology This cross-sectional study was conducted at King Abdulaziz Medical City in Riyadh. The BestCare system was used to collect patients' data between September 2020 and February 2022. JMP15 was used for data analysis. Frequencies and percentages were used for categorical data, and median and interquartile ranges were used for quantitative data. The chi-square and Kruskal-Wallis rank-sum tests were used to assess the difference between categorical and quantitative variables, respectively. Nominal logistical regression was used to assess diabetes as a risk factor for developing VTE among COVID-19 patients. Results Data from 153 admitted patients were collected after they satisfied the inclusion criteria. Of these patients, 39 (25.49%) developed VTE. The demographic data included age group, gender, and DM status presented as frequencies and percentages. Through bivariate analysis, patients with longer hospital stays had at least one episode of VTE (p = 0.0072). Using nominal logistic regression analysis, diabetes as a risk factor (odds ratio = 4.11, confidence interval = 0.955-5.05, p = 0.0287) was significantly associated with the development of VTE in COVID-19 patients. Conclusions Based on our study, diabetes proved significant when evaluating the possible factors regarding VTE development in COVID-19 patients. In addition, the length of stay also played a critical role in the severity of VTE in COVID-19 patients. Similar studies should be conducted on a national scale in Saudi Arabia to accomplish two goals: first, to gain further understanding of the impact of the variables investigated in our population, and second, to publish data that are more generalizable to the larger population of Saudi Arabia.

Spectrofluorometric determination of futibatinib in human plasma and pharmaceutical formulations.

Futibatinib is a powerful inhibitor of fibroblast growth factor receptors that impedes its phosphorylation and subsequently leading to a reduction in in cell viability across various cell lines. Futibatinib was approved for initial use as an effective treatment for several diseases, including non-small cell lung cancer and breast cancer. Herein, a novel selective fluorescence probe was created for futibatinib quantification in various matrices, including pharmaceutical formulation and human plasma. The technique primarily depends on futibatinib's chemical conversion into a fluorescent product through a reaction with trimethylamine and bromoacetyl bromide. The created fluorescent probe exhibits maximum emission peak at 338 nm upon excitation at 248 nm. The method provided a low detection limit of 0.120 ng/mL and maintained a linear concentration-dependent relationship across the range of 1-200 ng/mL. High sensitivity, accuracy and precision were demonstrated for futibatinib quantification in pharmaceutical formulation and spiked plasma matrix by the method, which was validated in accordance with ICH requirements.

Genome wide-scale CRISPR-Cas9 knockout screens identify a fitness score for optimized risk stratification in colorectal cancer.

BACKGROUND: The molecular complexity of colorectal cancer poses a significant challenge to the clinical implementation of accurate risk stratification. There is still an urgent need to find better biomarkers to enhance established risk stratification and guide risk-adapted treatment decisions. METHODS: we systematically analyzed cancer dependencies of 17 colorectal cancer cells and 513 other cancer cells based on genome-scale CRISPR-Cas9 knockout screens to identify colorectal cancer-specific fitness genes. A regression model was built using colorectal cancer-specific fitness genes, which was validated in other three independent cohorts. 30 published gene expression signatures were also retrieved. FINDINGS: We defined a total of 1828 genes that were colorectal cancer-specific fitness genes and identified a 22 colorectal cancer-specific fitness gene (CFG22) score. A high CFG22 score represented unfavorable recurrence and mortality rates, which was validated in three independent cohorts. Combined with age, and TNM stage, the CFG22 model can provide guidance for the prognosis of colorectal cancer patients. Analysis of genomic abnormalities and infiltrating immune cells in the CFG22 risk stratification revealed molecular pathological difference between the subgroups. Besides, drug analysis found that CFG22 high patients were more sensitive to clofibrate. INTERPRETATION: The CFG22 model provided a powerful auxiliary prediction tool for identifying colorectal cancer patients with high recurrence risk and poor prognosis, optimizing precise treatment and improving clinical efficacy.

Photo-Physical Characteristics of Janus Green B in Different Solvents and its Interaction Mechanism with Silver Nanoparticles.

This work explores the effects of solvent polarity on Janus Green B (JGB) photophysical properties. The Lippert-Mataga, Billot, and Ravi equations were utilized to calculate the singlet-state excited dipole moments (µe) and ground state dipole moments (µg) using absorption and fluorescence spectra analyses. The results showed an increase in the former, which is suggestive of electronic structural alterations upon excitation. Analysis of fluorescence quantum yield values revealed that JGB's environment had an impact on its emission characteristics; it was particularly sensitive to silver nanoparticles, suggesting possible interactions. While simulations of electron density, electrostatic potential, and energy gap (Eg) helped to understand the electronic structure of JGB, theoretical absorption spectra produced by Time Dependent Density Function Theory (TD-DFT) calculations offered insights into electronic transitions during absorption. To sum up, the present study contributes to our comprehension of the molecular behavior of JGB in various solvents by elucidating the intricate relationship among solvent polarity, molecular environment, and interactions with silver nanoparticles. Additionally, theoretical computations support the interpretation of experimental results.

Synthesis of novel phthalazine-based derivatives with potent cytotoxicity against HCT-116 cells through apoptosis and VEGFR2 inhibition.

The parent ethyl 3-(4-benzyl-1-oxophthalazin-2(1H)-yl) propanoate (3) has 25 compounds. Their respective mono, dipeptides and hydrazones derivatives were produced by chemoselective N-alkylation via addition reaction of 4-benzylphthalazin-1(2H)-one (2) with ethyl acrylate and anhydrous potassium carbonate to give ethyl 3-(4-benzyl-1-oxophthalazin-2(1H)-yl) propanoate (3). The ester 3 was hydrazinolyzed to give the corresponding hydrazide 3-(4-benzyl-1-oxophthalazin-2(1H)-yl) propanehydrazide (5), then azide 6 coupled with amino acid ester hydrochloride and/or amines to afford several parent esters 8a-c, then a series of hydrazinolyzed reactions occurred to give corresponding hydrazides 9a-c. The hydrazide 9a was subjected to the azide coupling procedure, which resulted in the formation of various dipeptides. Subsequently, it was condensed with various aldehydes to yield hydrazone derivatives 13a-d. Interestingly, compounds 9c, 12b, and 13c exhibited potent cytotoxicity with IC50 values of 1.58, 0.32 and 0.64 µM compared to sorafenib (IC50 = 2.93 µM). Compound 12b exhibited potent VEGFR2 inhibition by 95.2% with an IC50 value of 17.8 µM compared to sorafenib (94.7% and IC50 of 32.1 µM). For apoptosis activity, 12b-treatment induced apoptosis in HCT-116 cells by 21.7-fold, arresting the cell proliferation at S-phase. Finally, it formed a good binding affinity towards VEGFR2 protein with a binding energy of -10.66 kcal mol-1, and it formed binding interactions with the key interactive amino acids.

Clinical Practice of High-Flow Nasal Cannula Therapy in ARDS Patients: A Cross-Sectional Survey of Respiratory Therapists.

Background: High-flow nasal cannula (HFNC) is an essential non-invasive oxygen therapy in acute respiratory distress syndrome (ARDS) patients. Despite its wide use, research assessing the knowledge, practice, and barriers to using HFNC among respiratory therapists (RT) is lacking. Methods: A cross-sectional questionnaire was conducted among RTs in Saudi Arabia between December 19, 2022, and July 15, 2023. Data were analyzed as means and standard deviation or frequency and percentages. A Chi-square test was used to compare the differences between groups. Results: A total of 1001 RTs completed the online survey. Two-thirds of the respondents 659 (65.8%) had received training in using HFNC and 785 (78.4%) had used HFNC in clinical settings. The top conditions for HFNC indication were COVID-19 (78%), post-extubation (65%), and do-not-intubate patients (64%). Participants strongly agreed that helping maintain conversation and eating abilities (32.95%) and improving shortness of breath (34.1%) were advantages of HFNC. Surprisingly, 568 (57%) of RT staff did not follow a protocol for HFNC with ARDS patients. When starting HFNC, 40.2% of the participants started with FiO2 of 61% to 80%. Additionally, high percentages of RT staff started with a flow rate between 30 L/minute and 40 L/minute (40.6%) and a temperature of 37°C (57.7%). When weaning ARDS patients, 482 (48.1%) recommended first reducing gas flow by 5-10 L/minute every two to four hours. Moreover, 549 (54.8%) believed that ARDS patients could be disconnected from HFNC if they achieved a flow rate of <20 L/minute and FiO2 of <35%. Lack of knowledge was the most common challenge concerning HFNC implementation. Conclusion: The findings revealed nuanced applications marked by significant endorsement in certain clinical scenarios and a lack of protocol adherence, underscoring the need for uniform, evidence-based guidelines and enhanced training for RTs. Addressing these challenges is pivotal to optimizing the benefits of HFNC across varied clinical contexts.

Prevalence and determinants of non-communicable diseases and risk factors among adults in Lebanon: a multicentric cross-sectional study.

OBJECTIVES: Evidence on non-communicable disease (NCD) prevalence and associated risk factors informs primary health care consolidation regarding prevention and treatment strategies. In Lebanon, the government and many international organisations are still working to decrease the burden of NCDs. The aim of this study was to assess the prevalence of selected NCDs and their risk factors among adults in Lebanon, and to investigate the relationship between these risk factors and NCDs. STUDY DESIGN: A multicentric cross-sectional study was conducted over one year, from 1 June 2022 to 31 June 2023, across five Lebanese governorates. METHODS: Participants aged ≥18 years were considered eligible for enrolment in the study. Data on the sociodemographic, behavioural and medical characteristics of participants were collected. RESULTS: From the total study population (n = 4540), 52.4% reported one or more NCDs. The prevalence of most prominent NCDs were hypertension (32.8%), diabetes (26.8%), cardiovascular disease (16.1%), asthma (7.1%) and cancer (3.7%). Results showed a significant association between gender and smoking, high-fibre diet and asthma (P-value <0.05). Findings showed a highly significant association between age categories and smoking, high-fibre diet, physical activity, diagnosis with NCDs, hypertension, diabetes and cardiovascular disease (P-value <0.0001). CONCLUSIONS: This study showed a high prevalence of NCDs among adults living in Lebanon. Prevention, treatment and control of NCDs and their risk factors are a public health priority in Lebanon, and resources are required to provide targeted interventions with a multisectoral approach.

The prevalence and sociodemographic determinants of tobacco and nicotine use among students in healthcare disciplines in Saudi Arabian universities: a cross-sectional survey.

Background: Tobacco smoking is one of the most significant health-related problems worldwide. However, the prevalence and sociodemographic determinants of tobacco and nicotine use among students on healthcare courses in Saudi Arabia are limited. Methods: This cross-sectional study used a questionnaire that was distributed via SurveyMonkey between November 2022 and June 2023 to all student universities offering healthcare courses. Data are presented as frequency and percentages. The associated sociodemographic factors with current tobacco and nicotine use were subjected to logistic regression. Results: Overall, 5,012, of whom 3,872 (77.25%) were males, responded to the online survey. The prevalence of current tobacco and nicotine use was 3,553 (71%). The majority of users used electronic nicotine delivery systems (1,622: 32.36%). The current use of cigarettes (AOR: 1.75 (1.42 to 2.15)), e-cigarettes (AOR: 1.17 (1.01 to 1.37)), and smokeless tobacco substances (AOR: 1.35 (1.02 to 1.90)) were more pronounced among males compared to female students. However, the current use of a hookah was less among males (AOR: 0.74 (95% CI: 61 to 0.91)). Smoking cigarettes was practiced less among students living in other regions compared to the Central Region. However, smokeless tobacco substances seem to be more prevalent in the Western, Southern, and Northern Regions, (AOR: 1.57 (95% CI: 1.09 to 2.26)), (AOR: 1.43 (95% CI: 1.04 to 1.95)), and (AOR: 1.57 (95% CI: 1.09 to 2.26)), respectively. Conclusion: Smoking is prevalent among students in the healthcare disciplines, with electronic nicotine delivery systems being the most used product. Several sociodemographic factors were associated with higher tobacco or nicotine use.

Revolutionizing Treatment Strategies for Autoimmune and Inflammatory Disorders: The Impact of Dipeptidyl-Peptidase 4 Inhibitors.

DPP4 (Dipeptidyl-peptidase 4) a versatile protease, emerges as a prominent player in soluble and membrane-bound forms. Its heightened expression has been intimately linked to the initiation and severity of diverse autoimmune diseases, spanning rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (SSc), inflammatory bowel disease, autoimmune diabetes, and even SARS-CoV-2 infection. Operating as a co-stimulator of T cell activity, DPP4 propels T cell proliferation by binding adenosine deaminase (ADA), thereby augmenting the breakdown of adenosine-an influential inhibitor of T cell proliferation. However, the discovery of a wide range of DPP4 inhibitors has shown promise in alleviating these diseases' signs, symptoms, and severity. The available DPP4 inhibitors have demonstrated significant effectiveness in blocking DPP4 activity. Based on the characterization of their binding mechanisms, three distinct groups of DPP4 inhibitors have been identified: saxagliptin, alogliptin, and sitagliptin, each representing a different class. Elevated levels of angiotensin-converting enzyme 2 (ACE2) expression are associated with producing various coronavirus peptidases. With its anti-inflammatory properties, Sitagliptin may assist COVID-19 patients in preventing and managing cytokine storms. This comprehensive review delves into the burgeoning realm of DPP4 inhibitors as therapeutic interventions for diverse autoimmune diseases. With a discerning focus on their efficacy, the investigation sheds light on their remarkable capacity to alleviate the burdensome signs and symptoms intricately linked to these conditions.

Retrospective Cohort Study on Determinants of Mechanical Ventilation Duration of COVID-19 ICU Patients.

Background In the face of the ongoing global health crisis posed by COVID-19, it becomes imperative to understand the disease's dynamics, particularly in specific regions. This study provides a detailed examination of the factors influencing mechanical ventilation (MV) duration among COVID-19 patients in an intensive care setting, focusing on a diverse patient cohort from the Al Hassa region of Saudi Arabia. The primary aim of this study was to identify key demographic factors, clinical outcomes, and comorbidities that affect the duration of MV among ICU patients with COVID-19. This understanding is crucial for enhancing patient care and informing healthcare strategies in the context of the pandemic. Methods A retrospective cohort study was conducted involving patients diagnosed with COVID-19 and admitted to the ICU in the Al Hassa region. The total number of participants was 1,259. Using a systematic sampling method, these participants were chosen to create a representative sample that reflects the prevailing treatment protocols in ICUs across these hospitals. Data encompassed patient demographics, comorbidities, clinical outcomes, and MV duration. Statistical analyses were employed to explore the associations between these variables. Results Our findings reveal a total of 1,259 participants significant associations between MV duration and various factors, including nationality, legal status, travel history, and comorbidities like heart failure and immunocompromised status. These insights are instrumental in understanding the nuances of COVID-19 management in critical care. Conclusion The study provides valuable insights into the determinants of MV duration in severe COVID-19 cases, emphasizing the need for individualized patient care approaches. It highlights the complexity of managing COVID-19 in ICU settings and underscores the importance of tailored healthcare responses to this global health challenge, particularly in the Al Hassa region.

Quality of life tools among patients on dialysis: A systematic review.

Introduction:  The universal increase in obesity and diabetes has increased the chronic kidney disease (CKD) rate. In 2017, almost 800 million individuals suffered from CKD worldwide. Kidney dialysis becomes necessary as the disease progresses. Dialysis negatively impacts CKD patients' quality of life (QoL). It causes several complications that affect patients' physical, social, psychological, and spiritual aspects of life. This systematic review aims to identify condition-specific tools used to assess CKD patients' quality of life on dialysis. Material and Methods: A systematic literature search was conducted to investigate studies using QoL tools among patients on dialysis from February 2000 to June 2023. The search was conducted in several databases and followed the PRISMA guidelines. The focus was to identify tools that capture intrinsic factors, such as spiritual subdomains, rather than extrinsic factors, such as environmental subdomains. Results: The review identified five studies and seven dialysis-specific tools for assessing the QoL of CKD patients on dialysis. The physical domain was the most assessed, followed by the psychological and social domains. Fatigue, muscle weakness, sleep disorders, and pain were identified as the most common concerns in the physical domain. Conclusion: Dialysis negatively impacts all aspects of QoL in CKD patients. This review can guide clinicians in understanding the disease and treatment burden by identifying the most appropriate tools for assessing the QoL of adult CKD patients undergoing dialysis. There is a need for further studies to explore the detrimental effects of CKD treatment and better understand its impact on patients' QoL.

Assessment of Primary Healthcare Providers' Knowledge and Practices in Addressing Asymptomatic Hyperuricemia and Gout in the Asir Region of Saudi Arabia.

Introduction and aim Gout, the most common form of inflammatory arthritis, arises from hyperuricemia, a condition where elevated levels of uric acid lead to the deposition of monosodium urate (MSU) crystals in the joints. Nevertheless, it's important to note that not all cases of hyperuricemia result in gout. Methodology This cross-sectional study was conducted in the Asir region of Saudi Arabia, targeting primary healthcare physicians (PHPs) specializing in family medicine and general practice. The study utilized a modified electronic questionnaire, inspired by similar studies and aligned with recent guidelines, to assess PHPs' knowledge and practices concerning asymptomatic hyperuricemia (AH) and gout. The questionnaire encompassed the PHPs' demographic data and their knowledge and practices for AH and gout management. Results Out of 201 participating PHPs, the majority were male (68.2%), predominantly aged 25-34 years (73.1%), and practicing as general practitioners (61.2%). A significant proportion of PHPs had less than five years of experience (63.7%). In terms of education, 36.8% attended continuing medical education (CME) on AH or gout, and 66.7% were aware of the related management guidelines. The study revealed that the total knowledge score among PHPs averaged 5.18 out of seven, indicating a moderate level of knowledge. However, their practice level was moderate, with a mean practice score of 6.75 out of 12. The study also found no significant differences in knowledge scores based on gender, age, or years of experience, but significant variations were noted based on medical specialty. Conclusion There is a moderate level of knowledge and practice among PHPs in managing AH and gout in the Asir region. Despite adequate knowledge levels, there appears to be a gap in implementing this knowledge into practice, particularly in long-term management strategies. The findings emphasize the need for ongoing medical education and specialized training programs to bridge these gaps. The study provides a valuable framework for identifying and addressing similar challenges in other regions and medical practices.

Polyphenolic profile, processing impact, and bioaccessibility of apple fermented products.

Health-promoting foods have become increasingly popular due to intensified consumer interest and awareness of illnesses. There is a global market for apple fruits, which are affordable, nutritious, tasty, and produced in large quantities for direct consumption as well as food processing to make derived products. The food matrix of apples is suitable for fermentation, besides containing a high amount of phenolics and polyphenols. Fermentation of apples is one of the most common methods of preserving apple fruit and its byproducts. With different fermentation techniques, apple fruit can be used to make a wide range of products, such as fermented apple juice, cider, liqueurs, apple cider, apple vinegar and fermented apple solids, because it is not only a low-cost and simple method of processing the fruit, but it can also sometimes increase the bioavailability of nutrients and the levels of components that can improve health and sensory quality. To understand the health benefits of food products and how the fermentation process impacts polyphenols, it is also crucial to observe the effects of digestion on polyphenol bioaccessibility. Polyphenolic profile changes can be observed via both in vitro and in vivo digestion methods; however, in vitro digestion methods have the advantage of observing every step of gastrointestinal track effects and have less cost as well. In this review, the polyphenolic profile, processing impact, and bioaccessibility of apple-fermented products is assessed, with most available studies showing polyphenol profiles and bioaccessibility in apple varieties and fermented apple products.

Knowledge and practice of using airway pressure release ventilation mode in ARDS patients: A survey of physicians.

Background: Limited data is available on awareness and clinical management of the airway pressure release ventilation (APRV) mode of ventilation for acute respiratory distress syndrome (ARDS) patients among physicians who work at in adult critical areas. This study aimed to assess the knowledge and current practice of using APRV mode with ARDS patients and identify barriers to not using this mode of ventilation among physicians who work in adult critical areas in Saudi Arabia. Methods: Between November 2022 and April 2023, a cross-sectional online survey was disseminated to physicians who work in adult critical areas in Saudi Arabia. The characteristics of the respondents were analyzed using descriptive statistics. Percentages and frequencies were used to report categorical variables. Results: Overall, 498 physicians responded to the online survey. All responders (498, 100 %) reported that APRV is indicated in patients with ARDS, but 260 (52.2 %) did not know if there was an institutionally approved APRV protocol. Prone positioning was the highest recommended intervention by 164 (33.0 %) when a conventional MV failed to improve oxygenation in patients with ARDS. 136 (27.3 %) responders stated that the P-high should be set equal to the plateau pressure on a conventional ventilator while 198 (39.8 %) said that P-low should be 0 cmH2O. Almost half of (229, 46.0 %) responders stated that the T-high should be set between 4 and 6 s, while 286 (57.4 %) said that the T-low should be set at 0.4-0.8 s. The maximum allowed tidal volume during the release phase should be 4-6 ml/kg. Moreover, just over half (257, 51.6 %) believed that the maximum allowed P-high setting should be 35 cmH2O. One third of the responders (171, 34.3 %) stated that when weaning patients with ARDS while in APRV mode, the P-high should be reduced gradually to reach a target of 10 cmH2O. However, 284 (36.9 %) thought that the T-high should be gradually increased to reach a target of 10 s. Most responders (331, 66.5 %) felt that the criteria to switch the patient to CPAP would be to have an FiO2 ≤ 0.4, P-high ≤10 cm H2O, and T-high ≥10 s. Lack of training has been the most common barrier to not using APRV by 388 (77.9 %). Conclusion: There is a lack of consensus on the use of APRV mode, probably due to several barriers. While there were some agreements on the management of ventilation and oxygenation, there were variations in the selection of the initial setting of APRV. Education, training, and the presence of standardized protocols may help to provide better management.

The Prevalent Use of Complementary and Alternative Medicine Among Patients With Chronic Disease in the Al-Madinah Population of Saudi Arabia.

BACKGROUND: Global interest in complementary and alternative medicine (CAM) has recently risen, particularly in Saudi Arabia, and the use of CAM is gaining popularity as a healthcare option. OBJECTIVES: This study aims to assess the prevalence of CAM use among patients with chronic diseases and identify the reasons for resorting to CAM in Al-Madinah, Saudi Arabia. METHODS: A cross-sectional study was conducted in Al-Madinah City. Data for analysis were derived from 416 participants with chronic diseases. The data were collected using a valid, structured online questionnaire that was designed to extract socio-demographic data as well as data on the predominant use of herps, hijama (cupping), acupuncture, and other specific CAM applications. The collected data were analyzed using appropriate statistical methods. RESULTS: Of the 416 participants, 164 (39.4%) were men, and 96.9% were Saudi citizens. Approximately one-third of the studied participants had diabetes (34.1%), while 29.3%, 25.2%, 15.1%, and 12.3% had hypertension, obesity, asthma, and gastrointestinal tract disease, respectively. The prevalence of herb and natural supplement use was 89.2%. The most commonly used herbs and natural supplements were ginger (55.5%), honey and its derivatives (53.4%), cinnamon (45.4%), and frankincense (33.4%). Of the studied participants, 36.1% and 6.5% reported undergoing cupping and acupuncture, respectively. No statistically significant differences were found between the use of herbs and acupuncture or any of the studied factors. Further, the use of acupuncture exhibited no significant differences. However, the use of cupping displayed statistically significant differences in age, sex, and income among the participants. CONCLUSION: The prevalence of CAM use among patients with chronic diseases in Al-Madinah is high. It appears to play an essential role in health care, particularly in treating patients with chronic diseases in this population. Therefore, promoting research in the field of CAM is warranted.

Exploring factors influencing patient activation in Saudi rheumatoid arthritis patients: A Nationwide Cross-Sectional Survey-Results from the COPARA study.

OBJECTIVES: To evaluate patient activation in rheumatoid arthritis (RA) patients using patient activation measure 13 (PAM-13) on a national level in Saudi Arabia. METHOD: A national survey was administered across multiple centers in Saudi Arabia. Patient activation was assessed using the PAM-13. The Compliance Questionnaire for Rheumatology (CQR) and the RA Impact of Disease (RAID) tool were also administered. The data from the survey were analyzed, and the results were stratified based on activation level. All factors affecting patient activation were explored and reported. RESULTS: A total of 1241 participants were included. Most of the patients were females (85%), the mean age was 47 (±14), and most patients lived in the central region (47%). The mean (±standard deviation) patient activation score was 578.7 (±13.0). Patient activation was affected by multiple factors: demographic characteristics, such as education, with a beta value of 1.11 (95% confidence interval [CI] 0.64 ̶1.58, p < .001). Higher CQR scores were associated with higher activation levels, with a beta value of 2.61 (95% CI 0.80 ̶4.44, p = .005), and higher RAID scores were associated with lower activation levels, with a beta value of 3.13 (95% CI 1.36 ̶4.91, p = .001). CONCLUSIONS: Patient activation was affected by several demographic characteristics and the impact of RA. A higher activation may improve compliance. Future longitudinal studies are required to confirm these findings and should explore the underlying mechanism of these effects.

Exploring Impact of Multidisciplinary Care on Patient Activation in Saudi Rheumatoid Arthritis Patients: A Cross-Sectional Survey-Extended Results from the COPARA National Project.

Introduction: Multidisciplinary setting in healthcare provide positive patient outcomes. Objective: To evaluate the impact of specialized rheumatology clinics (multidisciplinary settings) on the activation and engagement of rheumatoid arthritis (RA) patients. Material and Methods: This cross-sectional survey assessed patient activation using the patient activation measure-13. Participants attending Specialized Rheumatology Clinics (SRC multidisciplinary clinics) were compared with age- and sex-matched patients attending Standard of Care (SOC). The study was observational in nature, assessing several demographic and therapeutic options and their relation to the clinical setting and patient activation. Results: This study included 117 SRC matched RA patients with 117 SOC. The majority of the included patients were female (n=211, 90.2%), >40 years of age (n=177, 75.6%), and had intermediate-to-high education (n=147, 62.8%). Patients in the SRC were also more likely to have activation levels 3 and 4 with an odds ratio of 3.194 (95% confidence interval [CI] 1.835-5.562, p<0.001). In addition, SRC participants were more likely to be in levels 3 and 4 activation, even after adjustment for confounding variables, with an adjusted odds ratio of 2.401 (95% CI 1.121-4.758, p=0.012) and 2.175 (95% CI 1.127-4.196, p=0.020), respectively. Conclusion: Establishing SRC for RA patients seems to have a positive impact on patient activation and engagement and adds to the previously explored benefits of multidisciplinary care in chronic disease management.

Role of prostanoids, nitric oxide and endothelin pathways in pulmonary hypertension due to COPD.

Pulmonary hypertension (PH) due to chronic obstructive pulmonary disease (COPD) is classified as Group 3 PH, with no current proven targeted therapies. Studies suggest that cigarette smoke, the most risk factor for COPD can cause vascular remodelling and eventually PH as a result of dysfunction and proliferation of pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs). In addition, hypoxia is a known driver of pulmonary vascular remodelling in COPD, and it is also thought that the presence of hypoxia in patients with COPD may further exaggerate cigarette smoke-induced vascular remodelling; however, the underlying cause is not fully understood. Three main pathways (prostanoids, nitric oxide and endothelin) are currently used as a therapeutic target for the treatment of patients with different groups of PH. However, drugs targeting these three pathways are not approved for patients with COPD-associated PH due to lack of evidence. Thus, this review aims to shed light on the role of impaired prostanoids, nitric oxide and endothelin pathways in cigarette smoke- and hypoxia-induced pulmonary vascular remodelling and also discusses the potential of using these pathways as therapeutic target for patients with PH secondary to COPD.

Association Between Musculoskeletal Pain and Studying Hours Among Medical Students in Jeddah, Saudi Arabia.

Introduction Musculoskeletal (MSK) disorders are one of the common health issues affecting people of various ages. The main risk factors for musculoskeletal pain are age, obesity, gender, level of education, psychosocial factors, occupational factors, decreased mobility and flexibility, and common factors such as consuming TV and video games. College students, especially medical students, are at a higher risk of these complaints as they have longer hours of studying than most faculties due to the competitiveness of their specialty. The objective of this study was to identify the relationship between musculoskeletal pain and studying hours in medical students in Jeddah, Saudi Arabia, and to increase awareness of this problem. Methods This cross-sectional study was conducted in 2022. Data was collected using an online questionnaire. A total of 314 participants were included in this study. The demographic variables, studying hours, studying locations, and postures were collected and analyzed. Results A total of 314 medical students were included in this study. The majority were males (71.0%) and, the mean age was 22.05±2.13 years. Most of them were sixth-year students, and most of them reported studying between three and four hours (40.1%), with the most common studying location reported being the students' home or residence (79.3%). The number of daily studying hours had no significant effect on the occurrence of musculoskeletal problems. Conclusion There was no significant relationship between the number of studying hours and the MSK pain. Clinical trials could be used to evaluate the most effective approaches to alleviate MSK pain in medical students.

Investigation of Simultaneous and Sequential Cooperative Homotropic Inhibitor Binding to the Catalytic Chamber of SARS-CoV-2 RNA-dependent RNA Polymerase (RdRp).

In our previous report, the unique architecture of the catalytic chamber of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), which harbours two distinctive binding sites, was fully characterized at molecular level. The significant differences in the two binding sites BS1 and BS2 in terms of binding pockets motif, as well as the preferential affinities of eight anti-viral drugs to each of the two binding sites were described. Recent Cryogenic Electron Microscopy (Cryo-EM) studies on the RdRp revealed that two suramin molecules, a SARS-CoV-2 inhibitor, bind to RdRp in two different sites with distinctive interaction landscape. Here, we provide the first account of investigating the combined inhibitor binding to both binding sites, and whether the binding of two inhibitors molecules concurrently is "Cooperative binding" or not. It should be noted that the binding of inhibitors to different sites do not necessary constitute mutually independent events, therefore, we investigated two scenarios to better understand cooperativity: simultaneous binding and sequential binding. It has been demonstrated by binding free energy calculations (MM/PBSA) and piecewise linear potential (PLP) interaction energy analysis that the co-binding of two suramin molecules is not cooperative in nature; rather, when compared to individual binding, both molecules adversely affect one another's binding affinities. This observation appeared to be primarily due to RdRp's rigidity, which prevented both ligands from fitting comfortably within the catalytic chamber. Instead, the suramin molecules showed a tendency to change their orientation within the binding pockets in order to maintain their binding to the protein, but at the expense of the ligand internal energies. Although co-binding resulted in the loss of several important key interactions, a few interactions were conserved, and these appear to be crucial in preserving the binding of ligands in the active site. The structural and mechanistic details of this study will be useful for future research on creating and developing RdRp inhibitors against SARS-CoV-2.