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There is emerging evidence suggesting that vitamin D and fibrinogen play contrasting roles in ACS pathophysiology and their combined impact, expressed as the vitamin D/fibrinogen ratio, can be a potential biomarker for ACS severity. This study aimed to investigate the relationship between vitamin D, fibrinogen, and their ratio with ACS types, and assess their potential as risk stratification biomarkers. This multicenter observational study was conducted in tertiary care hospitals in Afghanistan, Egypt, and Pakistan, including 300 ACS patients. Serum vitamin D and fibrinogen levels were measured using electrochemiluminescence immunoassay and the Clauss method, respectively. Statistical analyses included ANOVA, Kruskal-Wallis, post-hoc Games-Howell tests, Spearman's correlation, Fisher's Z-test, and multivariable logistic regression. Vitamin D levels were significantly lower (p < 0.001) and fibrinogen levels significantly higher (p < 0.001) in STEMI patients compared to NSTEMI and UA. The vitamin D/fibrinogen ratio showed a stronger correlation with ACS severity (Spearman's rho = -0.45, p = 0.01) than vitamin D alone (-0.41, p = 0.01), but this difference was not statistically significant (Fisher Z = 0.34, p = 0.73). Logistic regression revealed that a 1 nmol/L increase in vitamin D reduced ACS severity by 7.1% (p = 0.043), while a unit increase in the vitamin D/fibrinogen ratio reduced severity by 6.2% (p = 0.048). The contrasting effects of vitamin D and fibrinogen can prove useful biomarkers and modifiable risk factors for ACS. The superiority of the vitamin D/fibrinogen ratio over vitamin D only, however, needs further validation in larger studies.

Malnutrition increases bleeding risk by reducing thrombogenicity, impairing platelet aggregation, prolonging bleeding time, and promoting systemic inflammation, which affects vascular permeability and angiogenesis. The Prognostic Nutritional Index (PNI), calculated from serum albumin and lymphocyte count, reflects both nutritional and inflammatory status. This study aimed to assess PNI's association with bleeding risk in acute coronary syndrome (ACS) patients on dual antiplatelet therapy (DAPT). This prospective, single-center observational cohort study enrolled 1843 patients presenting with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). ROC analysis determined 42.7 as the optimal PNI cut-off value for risk stratification. Participants were stratified into distinct groups based on Prognostic Nutritional Index (PNI) cut-off values, a composite marker derived from serum albumin levels and peripheral lymphocyte counts, reflecting both nutritional and inflammatory status. Patients were prospectively followed for 12 months post-discharge to assess the occurrence of actionable bleeding events, with the aim of evaluating the association between PNI and post-PCI bleeding risk. The study cohort had a mean age of 66.4, with 65.16% male. After PCI, 98.04% were on DAPT. Patients were divided into Group I (PNI ≥ 42.7, n = 1290) and Group II (PNI < 42.7, n = 553). During follow-up, 5.58% of patients experienced actionable bleeding, with 3.5% in Group I and 10.3% in Group II (p < 0.0001). Multivariable Cox regression analysis revealed that PNI < 42.7 was a significant independent predictor of bleeding (HR: 1.7; 95% CI: 1.1-2.5; p < 0.003). Baseline PNI is an independent predictor of post-discharge bleeding in ACS patients on DAPT after PCI, suggesting it could be a valuable tool for risk stratification of bleeding in these patients.

Purpose: Coronary artery disease (CAD), clinically manifested as coronary syndrome (CS), is the leading cause of death and a significant contributor to morbidity worldwide. Elevated serum homocysteine levels have been associated with an increased risk of cardiovascular diseases, including CAD. Despite extensive research, the relationship between serum homocysteine and coronary syndromes with related short-term mortality is still under-studied. The main objective of this study is to evaluate the correlation between serum homocysteine levels and various types of CS, as well as in-hospital mortality in these patients. Patients and Methods: This multicenter study included 381 CS patients from Afghanistan, Egypt, and Pakistan tertiary care hospitals. The relation of serum homocysteine levels with different types of CS as well as with in-hospital mortality was measured and analyzed using inferential statistics (ANOVA, Kruskal--Wallis test, Tukey's post-hoc, Pearson correlation, etc.) and regression analysis (Binary regression). Results: Among 381 patients from both genders, 160 were from Pakistan, 130 from Egypt, and 91 from Afghanistan. There was no significant difference in baseline characteristics, like age, gender, homocysteine level, CS type, and mortality, among the three countries (p > 0.05). The one-way ANOVA, the Kruskal Wallis Test, and Tukey's post hoc test showed a significant difference among different CS groups based on serum homocysteine levels, and Pearson correlation showed a strong correlation between serum homocysteine and CS (r = 0.4). Binary regression analysis showed a 10.5% increase in in-hospital mortality for each 1 [micro]mol/L increase in homocysteine levels. Conclusion: Serum homocysteine could serve as a valuable biomarker and mortality predictor in CS patients. Keywords: serum homocysteine, coronary artery disease (CAD), coronary syndromes (CS), cardiac biomarkers, risk factors of CAD

Background/Objectives: Oncogenic KRAS drives ~30% of solid tumours, yet the only approved G12C-specific drugs benefit ≈ 13% of KRAS-mutant patients, leaving a major clinical gap. We sought mutation-agnostic natural ligands from Ziziphus lotus, whose stereochemically rich phenolics may overcome this limitation by occupying the SI/II (Switch I/Switch II) groove and locking KRAS in its inactive state. Methods: Phytochemical mining yielded five recurrent phenolics, such as (+)-catechin, hyperin, astragalin, eriodictyol, and the prenylated benzoate amorfrutin A, benchmarked against the covalent inhibitor sotorasib. An in silico cascade combined SI/II docking, multi-parameter ADME/T (Absorption, Distribution, Metabolism, Excretion, and Toxicity) filtering, and 100 ns explicit solvent molecular dynamics simulations. Pharmacokinetic modelling predicted oral absorption, Lipinski compliance, mutagenicity, and acute-toxicity class. Results: Hyperin and astragalin showed the strongest non-covalent affinities (−8.6 kcal mol−1) by forging quadridentate hydrogen-bond networks that bridge the P-loop (Asp30/Glu31) to the α3-loop cleft (Asp119/Ala146). Catechin (−8.5 kcal mol−1) balanced polar anchoring with entropic economy. ADME ranked amorfrutin A the highest for predicted oral absorption (93%) but highlighted lipophilic solubility limits; glycosylated flavonols breached Lipinski rules yet remained non-mutagenic with class-5 acute-toxicity liability. Molecular dynamics trajectories confirmed that hyperin clamps the SI/II groove, suppressing loop RMSF below 0.20 nm and maintaining backbone RMSD stability, whereas astragalin retains pocket residence with transient re-orientation. Conclusions: Hyperin emerges as a low-toxicity, mutation-agnostic scaffold that rigidifies inactive KRAS. Deglycosylation, nano-encapsulation, or soft fluorination could reconcile permeability with durable target engagement, advancing Z. lotus phenolics toward broad-spectrum KRAS therapeutics.

Purpose. To assess the visual, ocular, extraocular, and multifocal electroretinography (mfERG) outcomes of computer vision syndrome (CVS) among medical students. Methods. This study was designed as a cross-sectional case-control study that included 733 medical students. All students completed a specially designed and validated CVS questionnaire survey (CVS-F3). Students from the control (No-CVS) and CVS groups underwent comprehensive ophthalmic examinations including the mfERG examinations. Our main outcome measures included uncorrected and corrected distance visual acuity (UDVA and CDVA, resp.) measurements, subjective and cycloplegic refractions, slit-lamp examination, intraocular pressure measurement, pupillary reflexes tests, ocular movements’ tests, dry eye disease tests, and fundus and mfERG examinations. Results. The CVS-F3 identified that 87.9% of students had complaints that might be related to CVS. We documented a 76% prevalence rate in students undergoing an ophthalmologic exam. The most common ocular and extraocular complaints included visual blur and headache (40.9% and 46.8%, resp.). Statistical logistic and linear regression analyses showed that refractive errors, prolonged screen-hours, close eye-screen distance, improper gaze angle, poor screen-resolution, and screen-glare were risk factors for developing CVS and influencing its severity. In the mfERG subgroup, 42.5% demonstrated reduced amplitudes of mfERG rings and quadrants, indicating reduced foveal responses. Conclusion. Surveys cannot yield an accurate CVS prevalence. However, they help to identify subjects at risk who should be comprehensively assessed to confirm or exclude CVS diagnosis. Smartphone misuse primarily caused CVS among users. Our mfERG findings might be a sign of potential CVS visual sequelae; however, future studies are warranted. Clinicians need to understand these sequelae to appropriately identify and treat CVS.

Inducible nitric oxide synthase (iNOS) remains a demanding metallo-enzyme target because the catalytic heme shapes both geometry and electrostatics at the binding site. We evaluated the dietary flavonol glycoside isorhamnetin-3-O-glucoside (I3OG) against mouse (3E6T) and human (3E7G) iNOS oxygenase domains using a heme-aware, auditably validated docking workflow. we centered the docking grids at the crystallographic Fe position and validated the protocol by re-docking the native co-crystallized inhibitors (3E6T: AR-C118901/1A2; 3E7G: AR-C95791/AT2), reproducing the crystal poses with heavy-atom RMSD = 1.093 Å and 0.327 Å, respectively (≤ 2.0 Å criterion). Explicit-solvent 100-ns MD confirmed stable complexes for both systems; 3E6T showed tighter ligand RMSD, lower pocket Cα-RMSF, and a more persistent H-bond network. MM/GBSA over equilibrated frames (60−100 ns) yielded ΔG_bind ≈ −44.9 ± 3.9 kcal·mol −1 (3E6T) vs −36.1 ± 3.7 kcal·mol −1 (3E7G), with per-residue hot spots matching docking contacts. Principal-component free-energy maps indicated more focused minima for 3E6T and a broader low-energy valley for 3E7G, consistent with the MD metrics. we performed an apo-form heme-cavity test (heme removed, grid kept at Fe; proximal Cys re-protonated) to probe pocket occupancy/flexibility without claiming a catalytic model. Collectively, the heme-centred, co-crystal-validated protocol plus the apo-cavity readout support I3OG as a plausible scaffold for iNOS engagement and provide a transparent template for future metallo-enzyme docking studies.

BackgroundConcurrent neoadjuvant chemo-radiation (nCRT) with total mesorectal excision (TME) alone sometimes fails to cure lateral lymph node metastasis (LLNM). Therefore, additional lateral lymph node dissection (LLND) can help in the treatment of these patients. This is what we refer to as extended total mesorectal excision (eTME). Such operations (TME alone or eTME) can be performed using conventional laparoscopic techniques and robotic-assisted techniques as well. Our meta-analysis aims to compare the results of robot-assisted (R-eTME) versus laparoscopic-assisted extended mesorectal excision (L-eTME) in terms of short- and long-term outcomes.MethodologyDatabases searched using title and abstract included Medline (via PubMed), Web of Science, Scopus, and Embase, up to February 20, 2024. All studies that documented robotic versus laparoscopic procedures for extended total mesorectal excision (R-eTME versus L-eTME) and reported more than two relevant outcomes, were included in the study.ResultsOur meta-analysis demonstrates four significant outcomes (operative time, urinary complications, overall recurrence, and admission days) between the laparoscopic and robotic groups. The robotic approach shows advantages over the laparoscopic approach in these outcomes except for the operative time (minute), which was longer in the robotic group compared to the laparoscopic group. The laparoscopic group is associated with a higher overall recurrence than the robotic group with an Odds Ratio of 2(95% CI, 1–4, p = 0.05).ConclusionThis meta-analysis study showed that the R-eTME group had a lower recurrence rate compared to the L-eTME group. Additionally, hospital admission days increased significantly in the laparoscopic group. Other long-term outcomes did not differ significantly between the two groups. Short-term outcomes were similar, except for more urinary complications in the laparoscopic group. In conclusion, the study suggests that robotic surgery may offer advantages over laparoscopic surgery for eTME. Further research and analysis could provide further insight into the potential benefits of robotic surgery in this procedure, particularly when surgeon experience, center volume, and learning curve are taken into consideration.

Inflammatory processes are increasingly attributed to macrophage polarization. Proinflammatory macrophages promote T helper (Th) 1 response, tissue repair, and Th2 responses. Detection of macrophages in tissue sections is facilitated by CD68. Our study is focused on the expression of CD68 and the estimation of proinflammatory cytokines in children’s patients with chronic tonsillitis secondary to vitamin D supplementation. This hospital-based Randomized prospective case–control study was conducted on 80 children with chronic tonsillitis associated with vitamin D deficiency where (40 received vitamin D 50,000 IU weekly for 3–6 months and 40 received 5 ml distilled water as placebo). The serum 25-hydroxyvitamin D [25(OH)D] was measured using an Enzyme-linked immunosorbent assay on all included children. Different histological and immunohistochemical studies for the detection of CD68 were done. There was a significantly lower serum level of 25(OH)D in the placebo group versus the vitamin D group ( P  < 0.001). The levels of pro-inflammatory cytokines, TNFα, and IL-2 significantly increased in the placebo group as compared to the vitamin D group ( P  < 0.001). The increased level of IL-4 and IL-10 in the placebo group as compared to the vitamin D group was insignificant ( P  = 0.32, 0.82) respectively. Vitamin D supplementation alleviated the deleterious effect of chronic tonsillitis on the histological structure of the tonsil. Tonsillar tissues of the children in the control and vitamin D groups demonstrated a highly statistically significantly lower number of CD68 immunoexpressing cells compared with those in the placebo group ( P  < 0.001). Low vitamin D may play a role in chronic tonsillitis. Vitamin D supplementation could help reduce the occurrence of chronic tonsillitis in susceptible children.