Antifungal drug discovery for targeting Candida albicans morphogenesis through structural dynamics study.

In response to the escalating threat of drug-resistant fungi to human health, there is an urgent need for innovative strategies. Our focus is on addressing this challenge by exploring a previously untapped target, yeast casein kinase (Yck2), as a potential space for antifungal development. To identify promising antifungal candidates, we conducted a thorough screening of the diverse-lib drug-like molecule library, comprising 99,288 molecules. Five notable drug-like compounds with diverse-lib IDs 24334243, 24342416, 17516746, 17407455, and 24360740 were selected based on their binding energy scores surpassing 11 Kcal/mol. Our investigation delved into the interaction studies and dynamic stability of these compounds. Remarkably, all selected molecules demonstrated acceptable RMSD values during the 200 ns simulation, indicating their stable nature. Further analysis through Principal Component Analysis (PCA)-based Free Energy Landscape (FEL) revealed minimal energy transitions for most compounds, signifying dynamic stability. Notably, the two compounds exhibited slightly different behaviour in terms of energy transitions. These findings mark a significant breakthrough in the realm of antifungal drugs against C. albicans by targeting the Yck2 protein. However, it is crucial to note that additional experimental validation is imperative to assess the efficacy of these molecules as potential antifungal candidates. This study serves as a promising starting point for further exploration and development in the quest for effective antifungal solutions.Communicated by Ramaswamy H. Sarma.

The Prevalence and Associated Risk Factors for Neonatal Thrombocytopenia Among Newborns Admitted to the Neonatal Intensive Care Unit.

Background Thrombocytopenia is the most prevalent hematological condition in neonates that develops in the neonatal intensive care unit (NICU). This set of illnesses is caused by either decreased platelet production due to placental insufficiency, increased platelet breakdown (consumption), or a combination of the two causes. Based on platelet count, it is defined as mild, moderate, or severe thrombocytopenia, with early and late onset. Purpose The purpose of this study is to determine the prevalence of thrombocytopenia and the factors that contribute to it in newborns hospitalized in the neonatal critical care unit at the Maternity and Children Hospital in Al Ahsa, Saudi Arabia. Methods This descriptive retrospective cross-sectional study was carried out at the NICU of the Maternity and Children Hospital in Al Ahsa, Saudi Arabia, over the span of one year (August 2022 to August 2023) among hospitalized neonates with thrombocytopenia. Thrombocytopenia is defined as a platelet count of 150,000 or less. These patients were monitored until they recovered or died. Results The inclusion criteria were met by a total of 242 newborns with thrombocytopenia. Half of the neonates (57%) were full-term, with Apgar scores greater than 5 at the first (84%) and fifth (93%) minutes, respectively. The great majority of individuals (84%) experienced early-onset thrombocytopenia of mild severity (62%) and were asymptomatic (93%). The majority of the cases resolved spontaneously, with only 21% requiring platelet transfusion. There was a significant relationship discovered between gestational age and the severity of thrombocytopenia, with very preterm infants having moderate to severe thrombocytopenia, as well as birth weight (p=0.001). Furthermore, neonates with severe thrombocytopenia had a considerably higher mortality rate (p=0.001). Conclusion The mortality and morbidity of newborns with perinatal risk for neonatal thrombocytopenia can be reduced with timely detection of the cause and development of thrombocytopenia, as well as adequate and early care.

Assessing the Awareness and Understanding of Hospital Triage Among the General Population of Al-Ahsa, Saudi Arabia.

Background Hospital triage is a critical process in emergency departments (EDs) worldwide. The efficiency of the triage process significantly impacts the overall functioning of the ED and patient outcomes. However, the effectiveness of triage is not solely dependent on the healthcare professionals conducting it. The awareness and understanding of the triage process among the general population also play a crucial role. Methods This study aimed to assess the awareness and understanding of hospital triage among the general population of Al-Ahsa. A cross-sectional design was conducted in Al-Ahsa, Saudi Arabia, from July to September 2023. Data were collected using an online questionnaire. Results This study examined the awareness, understanding, attitude, and socio-demographic factors of hospital triage among 389 participants in Al-Ahsa, Saudi Arabia. Results showed that 59.4% (n=231) of participants were aware of emergency triage, with 91.8% (n=457) agreeing with patient classification based on deterioration. Expectations for waiting time varied, with 38.8% (n=151) expecting 5-10 minutes. Participants expressed positive attitudes, with 91% (n=354) believing triage improves patient care. Socio-demographic analysis revealed higher awareness among younger age groups, males, and highly educated individuals. Educational level was associated with participants' attitudes. These findings emphasize the importance of targeted awareness campaigns and improved waiting room amenities for effective hospital triage. Conclusion The study found that public awareness of emergency triage is average, with high satisfaction with the concept of patient classification based on deterioration. Periodic health education sessions regarding the importance of ER triage are recommended for healthcare visitors and staff.

Right ventricle to pulmonary artery conduit: a comparison of long-term graft-related events between bovine jugular vein conduit, aortic homograft, and porcine-valved conduits.

Background: The optimal conduit for right ventricle to pulmonary artery (RV-PA) reconstruction does not exist. Reinterventions are common due to conduit stenosis and endocarditis. Tailoring conduit choice according to patients' characteristics could improve the outcomes. The study aimed to compare graft-related events (infective endocarditis, transcatheter pulmonary valve replacement (PVR), transcatheter conduit dilatation, surgical conduit replacement, and transcatheter pulmonary branch intervention for RV-PA reconstruction using bovine jugular vein, aortic homograft, and porcine-valved conduits. Methods: In a retrospective cohort study, 155 patients with 193 procedures that were done in King Faisal Specialist Hospital and Research Center-Jeddah (KFSHRC JED) for implanting RV-PA conduits from 1999 to 2021 were included. The patients were grouped according to the type of conduit into 3 groups; Group 1 (n=153) received bovine jugular vein (BJVs) grafts, Group 2 (n=29) received aortic homografts, Group 3 (n=11) received porcine-valved conduits. Factors associated with graft-related events were evaluated using stepwise Cox regression analysis. Results: Patients with BJVs were significantly younger than those with porcine-valved conduits 3 (P=0.009). The weight of BJVs patients was significantly lower than homografts (P=0.002) and porcine-valved conduits patients 3 (P<0.001). The conduit size was as expected significantly lower in BJVs patients than patients who received porcine-valved conduits (P<0.001) and patients who received aortic homografts (P<0.001). There was no difference between Group 2 and 3 (P=0.084). Operative mortality occurred in 13 patients: 12 (7.84%) with BJV conduit and 1 (9.09%) with porcine valved conduit (P=0.351). Male gender [odds ratio (OR): 10.04; 95% confidence interval (CI): 1.28-78.86; P=0.028] and smaller conduit size (OR: 0.78; 95% CI: 0.61-0.99; P=0.048) were associated with increased operative mortality. Freedom from graft-related events at 5 and 10 years was 67% and 52% in BJVs patients, 74% and 36% in patients who received aortic homografts, and 53% in patients who received porcine-valved conduits. Factors associated with increased graft-related events were male gender (HR: 1.58; 95% CI: 1.004-2.50, P=0.048) and younger age (HR: 0.995; 95% CI: 0.991-0.999, P=0.041). Conclusions: RV-PA reconstruction was associated with low mortality, unrelated to the conduit type. Reinterventions for graft-related events were common. The durability and graft-related events might be comparable among BJV grafts, aortic homografts, and porcine-valved conduits. Factors associated with increased graft-related events in this study were male gender and younger age.

∆Np63α inhibits Rac1 activation and cancer cell invasion through suppression of PREX1.

ΔNp63α, a member of the p53 family of transcription factors, plays a critical role in maintaining the proliferative potential of stem cells in the stratified epithelium. Although ΔNp63α is considered an oncogene and is frequently overexpressed in squamous cell carcinoma, loss of ΔNp63α expression is associated with increased tumor cell invasion and metastasis. We recently identified a ΔNp63α/miR-320a/PKCγ signaling axis that regulates cancer cell invasion by inhibiting phosphorylation of the small GTPase Rac1, a master switch of cell motility that positively regulates cell invasion in multiple human cancers. In this study, we identified a novel mechanism by which ΔNp63α negatively regulates Rac1 activity, by inhibiting the expression of the Rac-specific Guanine Exchange Factor PREX1. ΔNp63α knockdown in multiple squamous cell carcinoma cell lines leads to increased Rac1 activation, which is abrogated by treatment with the Rac1 inhibitor NSC23766. Furthermore, ΔNp63α negatively regulates PREX1 transcript and protein levels. Using a Rac-GEF activation assay, we also showed that ΔNp63α reduces the levels of active PREX1. The inhibition of the PREX1-Rac1 signaling axis by ΔNp63α leads to impaired cell invasion, thus establishing the functional relevance of this link. Our results elucidated a novel molecular mechanism by which ΔNp63α negatively affects cancer cell invasion and identifies the ΔNp63α/Rac1 axis as a potential target for metastasis.

Transcription of a centromere-enriched retroelement and local retention of its RNA are significant features of the CENP-A chromatin landscape.

Centromeres depend on chromatin containing the conserved histone H3 variant CENP-A for function and inheritance, while the role of centromeric DNA repeats remains unclear. Retroelements are prevalent at centromeres across taxa and represent a potential mechanism for promoting transcription to aid in CENP-A incorporation or for generating RNA transcripts to maintain centromere integrity. Here, we probe into the transcription and RNA localization of the centromere-enriched retroelement G2/Jockey-3 (hereafter referred to as Jockey-3 ) in Drosophila melanogaster , currently the only in vivo model with assembled centromeres. We find that Jockey-3 is a major component of the centromeric transcriptome and produces RNAs that localize to centromeres in metaphase. Leveraging the polymorphism of Jockey-3 and a de novo centromere system, we show that these RNAs remain associated with their cognate DNA sequences in cis , suggesting they are unlikely to perform a sequence-specific function at all centromeres. We show that Jockey-3 transcription is positively correlated with the presence of CENP-A, and that recent Jockey-3 transposition events have occurred preferentially at CENP-A-containing chromatin. We propose that Jockey-3 contributes to the epigenetic maintenance of centromeres by promoting chromatin transcription, while inserting preferentially within these regions, selfishly ensuring its continued expression and transmission. Given the conservation of retroelements as centromere components through evolution, our findings have broad implications in understanding this association in other species.

Retraction: A Giant Porencephaly: A Rare Etiology of Pediatric Seizures.

[This retracts the article DOI: 10.7759/cureus.19623.].

Role of Arctiin in Fibrosis and Apoptosis in Experimentally Induced Hepatocellular Carcinoma in Rats.

Background and objectives Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor with a poor prognosis. It is currently the second most common cause of cancer-related mortality. Arctiin, a compound found in plants commonly used as a vegetable in Asian countries and as an ingredient in traditional European dishes, possesses various properties, including anti-proliferative, anti-senescence, anti-oxidative, anti-tumor, toxic, anti-adipogenic, and anti-bacterial effects. Our study aims to investigate the potential antitumor activity of arctiin against HCC in rats by inhibiting cell fibrosis and apoptosis. Methods Rats were induced with HCC by administering thioacetamide. Arctiin was orally administered to some rats twice a week for 16 weeks at a dose of 30 mg/kg. The liver impairment was evaluated by measuring serum α-fetoprotein (AFP) and examining liver sections stained with Masson trichrome or anti-hypoxia-induced factor-1α (HIF-1α) antibodies. The hepatic expression of messenger RNA and protein levels of HIF-1α, protein kinase C (PKC), extracellular signal-regulated kinase (ERK), ß-catenin, and mothers against decapentaplegic homolog 4 (SMAD4) were analyzed. Results Our study demonstrated that arctiin can potentially increase the survival rate of rats. This is achieved through a reduction in serum AFP levels and hepatic nodules. We also observed that arctiin has the ability to inhibit the formation of fibrotic tissues and necrotic nodules in HCC rats. Additionally, arctiin can significantly decrease the expression of HIF-1α, PKC, ERK, ß-catenin, and SMAD4. Conclusion Arctiin has demonstrated potential anti-tumor properties that could ameliorate HCC. Studies have shown that it may increase survival rates and reduce the number of tumors and AFP levels. Arctiin works by inhibiting HCC-induced hypoxia, thus blocking the expression of HIF-1α. It also helps to slow down tumor fibrosis by decreasing the expression of ß-catenin and SMAD4. Furthermore, arctiin has been found to downregulate PKC and ERK, reducing hepatic tissue apoptosis.

Prevalence of Hepatocellular Carcinoma in Hepatitis B Population within Southeast Asia: A Systematic Review and Meta-Analysis of 39,050 Participants.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a significant complication of hepatitis B and still poses a global public health concern. This systematic review and meta-analysis provide adequate details on the prevalence of HCC in the HBV population within Southeast Asian countries. METHOD: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria, a thorough search for literature discussing the prevalence of HCC in the HBV population within southeast Asia was performed. Eligible studies were subjected to a meta-analysis utilising a DerSimonian and Laird approach and a random effect model. A protocol was registered with PROSPERO (CRD42023423953). RESULT: Our study meticulously recovered 41 articles from seven countries in Southeast Asia, namely Cambodia, Indonesia, Malaysia, the Philippines, Singapore, Thailand, and Vietnam. A total of 39,050 HBV patients and 7479 HCC cases in southeast Asia were analysed. The pooled prevalence of HCC in HBV cases within southeast Asia was 45.8% (95% CI, 34.3-57.8%, I2 = 99.51%, p < 0.001). Singapore (62.5%, CI: 42.4-79.1) had the highest pooled prevalence of HCC in the HBV population compared to Vietnam, with the lowest estimate (22.4%, CI: 9.9-44.9). There was a drop in the pooled prevalence of HCC in HBV from 2016 until now (37.6%, CI: 19.2-60.5). CONCLUSION: The findings of this review reveal a high pooled prevalence of HCC in the HBV population and therefore stir the need for routine screening, management, and surveillance.

Characterizing Protein-Protein Interactions and Viscosity of a Monoclonal Antibody from Low to High Concentration Using Small-Angle X-ray Scattering and Molecular Dynamics Simulations.

Understanding protein-protein interactions and formation of reversible oligomers (clusters) in concentrated monoclonal antibody (mAb) solutions is necessary for designing stable, low viscosity (η) concentrated formulations for processing and subcutaneous injection. Here we characterize the strength (K) of short-range anisotropic attractions (SRA) for 75-200 mg/mL mAb2 solutions at different pH and cosolute conditions by analyzing structure factors (Seff(q)) from small-angle X-ray scattering (SAXS) using coarse-grained molecular dynamics simulations. Best fit simulations additionally provide cluster size distributions, fractal dimensions, cluster occluded volume, and mAb coordination numbers. These equilibrium properties are utilized in a model to account for increases in viscosity caused by occluded volume in the clusters (packing effects) and dissipation of stress across lubricated fractal clusters. Seff(q) is highly sensitive to K at 75 mg/mL where mAbs can mutually align to form SRA contacts but becomes less sensitive at 200 mg/mL as steric repulsion due to packing becomes dominant. In contrast, η at 200 mg/mL is highly sensitive to SRA and the average cluster size from SAXS/simulation, which is observed to track the cluster relaxation time from shear thinning. By analyzing the distribution of sub-bead hot spots on the 3D mAb surface, we identify a strongly attractive hydrophobic patch in the complementarity determining region (CDR) at pH 4.5 that contributes to the high K and consequently large cluster sizes and high η. Adding NaCl screens electrostatic interactions and increases the impact of hydrophobic attraction on cluster size and raises η, whereas nonspecific binding of Arg attenuates all SRA, reducing η. The hydrophobic patch is absent at higher pH values, leading to smaller K, smaller clusters, and lower η. This work constitutes a first attempt to use SAXS and CG modeling to link both structural and rheological properties of concentrated mAb solutions to the energetics of specific hydrophobic patches on mAb surfaces. As such, our work opens an avenue for future research, including the possibility of designing coarse-grained models with physically meaningful interacting hot spots.

Parent Awareness and Perceived Barriers Regarding Hearing Impairment among School Age Children in Taif Region of Saudi Arabia.

Background: Hearing impairment (HI) is the most common global disabling condition. It is a considerable public health condition in childhood that is associated with long-term socio-emotional-academic, and communication difficulties. The current study explored the knowledge and awareness of HI among school-age children and its related factor in Taif, Saudi Arabia. Materials and Methods: A cross-sectional study was done on 268 Saudi school-age children in the population of the Taif region of Saudi Arabia. A predesigned questionnaire was used to collect their demographic data, consanguinity, education level, and academic performance. Results: About 45.9% of parents had good awareness related to hearing loss and its impact on children's life. Only 19% (n = 51) of parents reported that their children encountered language problems in communicating with others. When we assessed the relationship between this language problem and academic performance, it was found that children with language problems had below-average academic performance (P < 0.001). Conclusion: The study showed that parents' awareness about children's hearing was not that satisfactory, and there was a considerable amount of difficulties faced by the children in their personal and social life due to these hearing problems. It is imperative to create awareness among the public regarding various modifiable risk factors of HI by conducting health awareness campaigns.

The Potential and Concerns of Using AI in Scientific Research: ChatGPT Performance Evaluation.

BACKGROUND: Artificial intelligence (AI) has many applications in various aspects of our daily life, including health, criminal, education, civil, business, and liability law. One aspect of AI that has gained significant attention is natural language processing (NLP), which refers to the ability of computers to understand and generate human language. OBJECTIVE: This study aims to examine the potential for, and concerns of, using AI in scientific research. For this purpose, high-impact research articles were generated by analyzing the quality of reports generated by ChatGPT and assessing the application's impact on the research framework, data analysis, and the literature review. The study also explored concerns around ownership and the integrity of research when using AI-generated text. METHODS: A total of 4 articles were generated using ChatGPT, and thereafter evaluated by 23 reviewers. The researchers developed an evaluation form to assess the quality of the articles generated. Additionally, 50 abstracts were generated using ChatGPT and their quality was evaluated. The data were subjected to ANOVA and thematic analysis to analyze the qualitative data provided by the reviewers. RESULTS: When using detailed prompts and providing the context of the study, ChatGPT would generate high-quality research that could be published in high-impact journals. However, ChatGPT had a minor impact on developing the research framework and data analysis. The primary area needing improvement was the development of the literature review. Moreover, reviewers expressed concerns around ownership and the integrity of the research when using AI-generated text. Nonetheless, ChatGPT has a strong potential to increase human productivity in research and can be used in academic writing. CONCLUSIONS: AI-generated text has the potential to improve the quality of high-impact research articles. The findings of this study suggest that decision makers and researchers should focus more on the methodology part of the research, which includes research design, developing research tools, and analyzing data in depth, to draw strong theoretical and practical implications, thereby establishing a revolution in scientific research in the era of AI. The practical implications of this study can be used in different fields such as medical education to deliver materials to develop the basic competencies for both medicine students and faculty members.

Prodromal Symptoms in Patients Presenting With Myocardial Infarction.

Background Prodromal symptoms are warning signs of an impending acute myocardial infarction (AMI). However, they are often overlooked by both patients and primary clinicians, and little is known about them. Therefore, this study aims to assess the frequency and types of prodromal symptoms in patients with AMI. Methodology This descriptive cross-sectional study was conducted at a tertiary care cardiac center. Consecutive patients diagnosed with AMI within the last week were evaluated for prodromal symptoms. The prodromal symptoms included chest pain, chest heaviness, chest burning, palpitations, fatigue, sleep disturbance, shortness of breath (SOB), dizziness, anxiety, sudden heat or cold, back pain, and vomiting. Results In a sample of 242 patients, 79.6% were males, with a mean age of 54.7 ± 12.2 years, and 179 (74%) were diagnosed with ST-segment elevation myocardial infarction (STEMI). Among the participants, 142 (58.7%) showed no prodromal symptoms. Among those with prodromal symptoms, chest pain was the predominantly reported prodromal symptom with a frequency of 68%, followed by chest heaviness at 44%, palpitations at 42%, shortness of breath at 34%, and chest burning at 27%. Unusual fatigue in 23% and sleep disturbance in 22% of the patients were also reported. Conclusion The findings from this study revealed that prodromal symptoms were present in a significant proportion of acute myocardial infarction (MI) cases, with more than four in 10 patients reporting these early warning signs. The most commonly observed prodromal symptoms were chest pain, chest heaviness, palpitations, shortness of breath, and chest burning. The timely identification of these symptoms can help prevent infarction, thereby reducing the burden of heart failure and other related mortalities.

Subclass Effects on Self-Association and Viscosity of Monoclonal Antibodies at High Concentrations.

The effects of a subclass of monoclonal antibodies (mAbs) on protein-protein interactions, formation of reversible oligomers (clusters), and viscosity (η) are not well understood at high concentrations. Herein, we quantify a short-range anisotropic attraction between the complementarity-determining region (CDR) and CH3 domains (KCDR-CH3) for vedolizumab IgG1, IgG2, or IgG4 subclasses by fitting small-angle X-ray scattering (SAXS) structure factor Seff(q) data with an extensive library of 12-bead coarse-grained (CG) molecular dynamics simulations. The KCDR-CH3 bead attraction strength was isolated from the strength of long-range electrostatic repulsion for the full mAb, which was determined from the theoretical net charge and a scaling parameter ψ to account for solvent accessibility and ion pairing. At low ionic strength (IS), the strongest short-range attraction (KCDR-CH3) and consequently the largest clusters and highest η were observed with IgG1, the subclass with the most positively charged CH3 domain. Furthermore, the trend in KCDR-CH3 with the subclass followed the electrostatic interaction energy between the CDR and CH3 regions calculated with the BioLuminate software using the 3D mAb structure and molecular interaction potentials. Whereas the equilibrium cluster size distributions and fractal dimensions were determined from fits of SAXS with the MD simulations, the degree of cluster rigidity under flow was estimated from the experimental η with a phenomenological model. For the systems with the largest clusters, especially IgG1, the inefficient packing of mAbs in the clusters played the largest role in increasing η, whereas for other systems, the relative contribution from stress produced by the clusters was more significant. The ability to relate η to short-range attraction from SAXS measurements at high concentrations and to theoretical characterization of electrostatic patches on the 3D surface is not only of fundamental interest but also of practical value for mAb discovery, processing, formulation, and subcutaneous delivery.

Coexistence of Oncocytic (Hürthle cell) carcinoma with foci of anaplastic carcinoma and a metastasizing papillary carcinoma in one thyroid gland: Rare case report.

INTRODUCTION AND IMPORTANCE: Anaplastic thyroid cancer is considered one of the most fatal aggressive malignancies with a survival duration estimated in months. When compared to anaplastic thyroid cancer, a well-differentiated thyroid tumor has a better prognosis and a longer survival duration even if it metastasized. Left untreated, the transformation of well-differentiated thyroid carcinoma to aggressive anaplastic malignancy has been considered one of the most devastating complications. CASE PRESENTATION: A 60-year-old male presented with a complaint of anterior neck swelling and hoarseness examination revealed a huge left thyroid swelling that was mobile, not tender, not attached to the underlying structures. Ultrasonographic examination of the thyroid gland showed a massively enlarged left thyroid lobe. Fine needle aspiration revealed undifferentiated (anaplastic) thyroid carcinoma. Preoperative CT excluded invasion or metastasis, and patient underwent total thyroidectomy and level 6 lymph node dissection. Histopathology showed anaplastic carcinoma foci within a background of Oncocytic (Hürthle cell) carcinoma and an incidental papillary thyroid carcinoma metastasizing into one lymph node. CLINICAL DISCUSSION: The predominance of an anaplastic thyroid tumor with a few foci of well-differentiated thyroid malignancy, although rare, is the known commonly observed histopathological finding. However, it is extremely rare to find Oncocytic (Hürthle cell) thyroid carcinoma within the anaplastic component. It's presumed that patients who have coexisting well-differentiated thyroid cancer with the anaplastic component are at an overall survival advantage when compared to those who have pure anaplastic thyroid cancer. Our patients had a predominantly well-differentiated component, with a ratio of 80/20, the lesser being anaplastic, which might explain his 10 months cancer free outcome. CONCLUSION: It's extremely rare to encounter a predominant Oncocytic (Hürthle cell) carcinoma with foci of anaplastic tumor and a separate papillary carcinoma that metastasized to one lymph node. This rare histopathological finding supports that theory of anaplastic transformation from a pre-existing well differentiated thyroid tumor.

Refeeding Syndrome Awareness among Physicians of King Abdullah Medical City in Makkah, Saudi Arabia.

BACKGROUND: Refeeding syndrome (RFS) is a lethal condition of metabolic disturbances that arise from the sudden switch of metabolism from a state of starvation to one of nourishment. Quick recognition would reduce health complications. Physicians who are unaware of the syndrome will not identify and treat it. As nutritional risk is associated with the risk of RFS, physicians should be aware of it. AIM: To determine whether the physicians of King Abdullah Medical City (KAMC) in Makkah know of RFS and, if so, have skills in diagnosis and managing the syndrome. METHODS: One hundred and fifty-nine physicians of KAMC were recruited in a cross-sectional study. They were asked to complete a questionnaire by face-to-face interview. The questionnaire was designed to capture physicians' knowledge and ability to manage RFS based on the awarding of certain scoring points. RESULTS: The level of knowledge among physicians had a significant association between knowledge and age (p = 0.021) and medical specialty (p = 0.010). Additionally, the most knowledgeable physicians were those who work in critical care (21.4%). Around 18% of physicians were not able to manage RFS. CONCLUSIONS: Lacking knowledge of RFS and how to manage it leads to critical life-threatening complications. Physicians need nutritional education to help them diagnose RFS and consult dietitians to avoid its complications.

Association between proton pump inhibitors and rhabdomyolysis risk: a post-marketing surveillance using FDA adverse event reporting system (FAERS) database.

Background: This research aims to explore and compare the signals of rhabdomyolysis from the use of Proton pump inhibitors (PPIs) using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Rhabdomyolysis and related terms submitted between 2013 and 2021 were retrieved from the FAERS database. The data were analyzed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Empirical Bayes Geometric Mean (EBGM) and the information component (IC). The signals of rhabdomyolysis associated with PPIs use were detected in both 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) utilizers and non-utilizers. Results: A total of 7,963,090 reports were retrieved and analyzed. Fifty-seven reports linked PPIs to rhabdomyolysis out of 3670 reports from other drugs (non-statin included). The association of rhabdomyolysis and PPIs was significant in both statins included, and non-statin-included reports, although with varying degrees of association. The ROR was 2.5 (95% confidence interval [CI] 1.9-3.2) for PPIs in non-statin-included reports and 2 (95% CI: 1.5-2.6) for PPIs in statin-included reports. Conclusion: Significant signals of rhabdomyolysis were associated with PPIs. However, its signals were higher in non-statin-included reports compared to statin-included reports. Plain Language Summary: Plain language summaryProton Pump Inhibitors and rhabdomyolysis risk Background: The FDA created the FDA Adverse Event Reporting System (FAERS) database to support post-marketing surveillance programs. The FAERS is a computerized database with more than nine million adverse event reports, including all reports from 1969 to the present. This research aims to explore and compare the signals of rhabdomyolysis from the use of proton pump inhibitors (PPIs) using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.Research design and methods: We retrieved rhabdomyolysis and related terms submitted between 2013 and 2021 from the FAERS database. Then, we analyzed the data that we found. We detected the signals of rhabdomyolysis associated with PPIs use in both statins utilizers and non-utilizers.Results: We retrieved and analyzed a total of 7,963,090 reports. We found 57 reports linked PPIs to rhabdomyolysis out of 3670 reports from other drugs (non-statin included). The association of rhabdomyolysis and PPIs was significant in both statins included, and non-statin-included reports, although with varying degrees of association.Conclusion: Significant signals of rhabdomyolysis were associated with PPIs. However, its signals were higher in non-statin-included reports than in statin-included reports.

Comparison of Different Antiviral Regimens in the Treatment of Patients with Severe COVID-19: A Retrospective Cohort.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disorders, with disease severity ranging from asymptomatic to critical manifestations. The current retrospective study compared the efficacies of different antiviral regimens used in patients suffering from severe COVID-19 disease from 19 January 2020 to December 2021 in a single center in Saudi Arabia. In total, 188 patients were enrolled in the current study, including 158 patients treated with different antiviral regimens, and 30 who did not receive any antiviral treatment. Different antiviral regimens, including favipiravir, remdesivir, oseltamivir, favipiravir/remdesivir, and favipiravir/oseltamivir were adopted. The effects of using different antivirals and antibiotics on the survival rate were evaluated, as well as the presence of comorbidities. Among all severely affected patients, 39/188 (20.7%) survived. Both age and comorbidities, including diabetes and hypertension, were significantly correlated with high case fatality following SARS-CoV-2 infection. Remdesivir alone and the combination of favipiravir and remdesivir increased the survival rate. Surprisingly, both imipenem and linezolid helped in the deterioration of disease outcome in the patients. A negative correlation was detected between increased mortality and the use of favipiravir and the use of either imipenem or linezolid. Among the compared antiviral regimens used in the treatment of severe COVID-19, remdesivir was found to be an effective antiviral that reduces COVID-19 case fatality. Antibiotic treatment using imipenem and/or linezolid should be carefully re-evaluated.

Co-exposure to commercial food product ingredient E341 and E551 triggers cytotoxicity in human mesenchymal stem cells.

Several nano-toxicological studies have assessed the prospective health risks of engineered nanostructures. Still, nanoscale ingredients from food products are not explored well, and only a few have attended to the possible effects of food additive-based nanoparticles in food. The physicochemical properties of food additives and their fate on human health are still unknown. To fill this knowledge gap, we examined the physicochemical characteristics of food product isolate E341/E551. Additionally, we assessed the consequence of these nanoscale E341 and E551 as co-exposure on human mesenchymal stem cells (hMSCs). The transmission electron microscope (TEM) images revealed that food product isolate (E341/E551) consists of nanoscale particles. The E551 and E341 have 20-50 nm and 70-200 nm diameters, respectively. Co-exposure of food additives SiO2 (E551) and Tricalcium phosphate (E341) effect on the cell viability, morphology, mitochondrial membrane potential, and reactive oxygen species (ROS) level of hMSCs were studied. The cell viability reduction, mitochondrial membrane potential loss, and ROS generation in E341/E551 co-exposed cells were observed. Our study suggests that E341/E551 co-exposure elevated the ROS level and mitochondrial membrane potential depletion at a high dose. The oxidative stress-related genes MDM3, TNFSF10, and POR have exhibited significant upregulation in the E341/E551 treatment group. These results conclude that long-term over-exposure to E341/E551 may be triggers health risks in a human. Further in vivo studies are required for food industry implications due to nanoscale ingredients in E341 and E551.

Comparing Surgical Techniques for Meniscal Tears: A Systematic Review of Radiographic and Functional Outcomes.

Meniscal tears are a common orthopedic injury. The management approaches for meniscal tears include both surgical and non-surgical procedures; however, the majority of the surgeons opt for various surgical interventions. This systematic review aimed to compare the outcomes of different surgical techniques for meniscal tears. The systemic search was carried out in various databases including PubMed, Web of Science, CINAHL, and Scopus. Studies that investigated surgical techniques for meniscal repair and published between 2010 to 2023 were included. Out of the 7,421 potential studies identified from databases and Google Scholar search, only 17 studies were included in our systemic review. The follow-up periods ranged from 6 weeks to 123 months. Adverse effects were reported in some studies, including joint line tenderness, swelling, and loss of flexion, while others reported no significant adverse events. Pull-out repair and refixation techniques demonstrated better clinical outcomes and slower arthritic progression than partial meniscectomy. Mason-Allen stitches and simple stitches yielded comparable results, and both inside-out and all-inside techniques had similar clinical and functional outcomes. This systematic review provides valuable insights into the outcomes of different surgical techniques for meniscal tears. Further studies with longer follow-up periods may help assess the long-term effectiveness of these surgical techniques.