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Remdesivir, a competitive inhibitor of viral RNA-dependent RNA polymerase, is the drug of choice for anti-COVID-19 treatment. However, the instability of these substances in plasma raises doubts about their therapeutic potency. Additionally, SARS-CoV-2-infected cells may exhibit a variety of antiviral behaviors due to intricate activation pathways. Therefore, this study aimed to develop a synthesis for the remdesivir derivative. The remdesivir derivative was synthesized using acetyl chloride as a reagent in a ratio of 1:3 in dichloromethane and tetrahydrofuran solvent at 30°C for 6 h. Thin-layer chromatography and spectrophotometers (1H NMR and 13C NMR) were used to identify the produced molecule, which was a brownish-yellow crystalline powder. The results of the synthesis yielded 0.8 gr (77.34%), and the Rf value of the remdesivir derivate was 0.54. The characterization with 1H NMR at δ2.5 ppm (3H, s) indicated the presence of a proton in the H-C-C=O structure caused by the substitution of the acetyl group in the remdesivir structure. The 13C NMR data indicated the presence of aromatic carbons, alkenes, C≡N, and carbon bonds with electronegative O. This remdesivir derivate chemical can be a potential candidate for an anti-COVID-19 drug that has more potency because it has substitutions of acetyl groups at positions 2' and 3' in the structure of remdesivir. [ABSTRACT FROM AUTHOR]

Gout is a pathological condition caused by monosodium urate crystal deposition in tissues. Allopurinol, the first-line therapy, inhibits xanthine oxidase but may be ineffective due to reduced conversion to oxypurinol (OXY). Current delivery routes for OXY, including oral and intravenous routes, have drawbacks such as poor solubility and patient discomfort. This study developed a delivery system integrating thermosensitive gel (TRG) containing OXY with polymeric solid microneedles (PSMNs). Molecular docking demonstrated high-affinity binding interactions between OXY and Pluronic (-2.5). The TRG, formulated with Pluronic F127 and F68, was assessed for gelation temperature, pH, spreadability, and bioadhesive strength. PSMN, made from poly(vinyl alcohol) and polyvinylpyrrolidone K-30 with citric acid, was evaluated for mechanical strength and skin penetration. In vitro hemolysis activity, drug release, and ex vivo permeation studies were conducted. Molecular docking results showed stable binding with an affinity of -2.5 between the ligands of OXY and Pluronic. The TRG formulation exhibited promising characteristics for transdermal drug delivery. PSMN demonstrated good mechanical strength and was able to penetrate up to 504 μm. Hemolysis testing showed that PSMN and TSG were safe with a hemolysis ratio of less than 5%. In vitro drug release studies showed a high OXY release of 2.24 ± 0.26 mg with the highest concentration of Pluronic F68, displaying a sustained release profile. Ex vivo permeation studies showed a significant difference ( p < 0.05) between OXY permeation without and with PSMN combination. PSMN increased OXY permeation by 79-81% compared to permeation without PSMN. This study successfully developed a TRG formulation combined with PSMN to enhance transdermal delivery of OXY. These results suggest a promising new route for OXY delivery, potentially offering a more efficient and user-friendly treatment for chronic gout. Further in vivo studies are needed to evaluate the efficacy, pharmacokinetics, pharmacodynamics, drug interactions, and toxicity for further clinical applications., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Anomalous aortic origin of the right coronary artery (RCA) is a rare anatomic anomaly that is present in ~1% of the general population, and is often discovered incidentally through imaging performed for another purpose. Despite being an uncommon phenomenon, aberrant right coronary arterial origins can have devastating manifestations in half of affected patients. These include myocardial infarction, arrhythmias, heart failure, syncope, and sudden cardiac death secondary to ischemia of the cardiac tissue. This report describes a case of a 48-year-old female patient that was initially found to have ST-elevation myocardial infarction. During cardiac catheterization, the patient was discovered to have a type A aortic dissection. Cardiothoracic surgery was consulted, and she was immediately transferred to the operating room for repair. During the procedure, an anomalous RCA was discovered with its origin in the dissected tissue, which was initially ligated and then bypassed using greater saphenous vein graft., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

This brief report discusses the diagnosis, management and surgical intervention of a man in his 30s presenting with a rare traumatic sternal manubrium dislocation following a motorcycle crash, accompanied by multiple concomitant rib fractures. The severity and complexity of the patient's injuries necessitated an operative approach for his sternomanubrial dislocation, emphasising the importance of multidisciplinary coordination, accurate diagnosis and prompt surgical intervention. The report provides valuable insights into the successful application of open reduction and internal fixation with plating in a real-world setting, which resulted in positive patient outcomes, despite the rarity and severity of this type of trauma. It further underscores the need for additional research to advance best practices for managing traumatic sternal manubrium dislocations in the context of high-impact injuries., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

We present the case of a 41-year-old man with an anterior mediastinal mass and constellation of clinical symptoms, including dyspnea, pleural effusions, pericardial effusions, renal insufficiency, and pancytopenia. After inconclusive results on several laboratory tests and a nondiagnostic surgical biopsy specimen, a specimen from a second surgical biopsy identified the patient's condition as Castleman disease associated with TAFRO (thrombocytopenia, anasarca, fevers, reticulin myelofibrosis, organomegaly) syndrome. This case highlights the importance of obtaining large tissue biopsy samples, interval follow-up, and acknowledging cognitive biases.

Gradenigo syndrome comprises a clinical triad: retro-orbital pain, sixth cranial nerve palsy, and purulent otorrhea. This clinical syndrome often arises secondary to petrous apicitis, which is an infection of the petrous apex that may result from the contiguous spread of infection from the ear or mastoid. This syndrome is very rare, and based on the existing literature, the initial approach for treatment involves long-term administration of IV antibiotics, which may resolve the underlying infection related to petrous apicitis, mastoiditis, and/or otitis media. In this case, the patient, a 69-year-old male, had a progression of several symptoms, including recurrent headaches, diplopia, hearing loss, and dysphagia, despite long-term antibiotic therapy and a prior mastoidectomy. Thus, the neurosurgical team decided to intervene via anterior petrous bone resection via the Kawase approach, which unfortunately did not result in the resolution of the patient's symptoms. The patient continued to have symptoms of Gradenigo syndrome, including sixth cranial nerve palsy and was subsequently referred to outpatient follow-up for further management. In this report, we present the patient's case and a brief review of the literature concerning various treatment modalities for Gradenigo syndrome., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Rifai et al.)

Objective: Acne vulgaris (AV) is a common problem with a relatively high incidence rate among Asian people. The potential antimicrobial and anti-inflammatory properties of banana peels have been demonstrated in previous studies but have not been studied in cases of AV. Therefore, this study was aimed at investigating the protective effects of banana ( Musa balbisiana ) peel extract (MBPE) against AV., Methods: Thirty rats were divided into five groups (n = 6 rats per group): an AV group, AV group treated with 0.15% MBPE, AV group administered 0.30% MBPE, AV group administered 0.60% MBPE, and AV group administered clindamycin (the standard drug treatment). We assessed nodule size, bacterial count, histopathology, and cytokine levels (IL-1α, IFN-γ, tumor necrosis factor (TNF)-α, and IL-8). Enzyme linked immunoassays were used to measure the cytokine levels. In addition, we performed molecular docking studies to determine the interactions between phytochemicals (trigonelline, vanillin, ferulic acid, isovanillic acid, rutin, and salsolinol) via the Toll-like receptor 2 (TLR2) and nuclear factor-kappa B (NF-κB) pathways., Results: All MBPE treatment groups, compared with the AV group, showed suppression of both bacterial growth and proinflammatory cytokine production, as well as resolved tissue inflammation. The nodule size was significantly suppressed in the groups receiving the two highest doses of MBPE, compared with the AV group. However, the pharmacological action of MBPE remained inferior to that of clindamycin. Docking studies demonstrated that rutin was the phytocompound with the most negative interaction energy with TLR2 or NF-κB., Conclusions: Our results indicated that MBPE has anti-inflammatory effects against AV, by suppressing nodule formation, inhibiting bacterial growth, and decreasing proinflammatory cytokine production., (© 2023 The Authors.)

This article discusses the prevalence of depression in patients with intracranial hemorrhage (ICH) and the relationship of selective serotonin reuptake inhibitor (SSRI) use with bleeding risk. A detailed account of the patient's psychiatric history and current hospital admission is also provided. This article then further explores the pathophysiological mechanisms that contribute to depression in ICH patients, the effect of SSRIs on outcomes in patients with ICH, and ways to treat depression in ICH patients. Based on the literature, the conclusion is that practitioners should avoid SSRIs in ICH patients with certain genetic markers and treat depression as seriously as one would treat a physical ailment. Ultimately, more research is necessary to explore how to treat depression in this patient population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Rifai et al.)

3',6-dimethoxy-3'',4''-(methylenedioxy)-2,5-epoxylignan-4'-ol (DMEO), an epoxylignan isolated from Piper nigrum , has currently captured attention for its potential antitumor effect. However, low stability is limiting its therapeutic application. The application of nanocapsulation would be the main strategy for overcoming this problem. DMEO-loaded nanocapsules were prepared by an emulsion-diffusion method using Eudragit RL 100 (at concentrations of 1, 1.5 and 2%) and polyvinyl alcohol. As the polymer content increased, the encapsulation efficiency and mean particle size also increased. After 6 months of storage at 25°C (0% RH), no crystalline peaks were observed in the diffraction patterns of all nanocapsules, thereby suggested that the physical stability of nanoencapsulated DMEO was not affected by the concentration ratio of the polymer-stabilizer combinations., Competing Interests: No competing interests were disclosed.

Acute pancreatitis (AP) is associated with significant morbidity and mortality; however, there is no specific treatment for this disease. A novel salivary tripeptide analog, feG, reduces inflammation in several different animal models of inflammation. The aims of this study were to determine whether feG reduced the severity of AP and modifies the expression of pancreatic ICAM-1 mRNA during AP in a mouse model. AP was induced in mice by hourly (x12) intraperitoneal injections of caerulein. A single dose of feG (100 microg/kg) was coadministered with caerulein either at time 0 h (prophylactic) or 3 h after AP induction (therapeutic). Plasma amylase and pancreatic MPO activities and pancreatic ICAM-1 mRNA expression (by RT-PCR) were measured. Pancreatic sections were histologically assessed for abnormal acinar cells and interstitial space. AP induction produced a sevenfold increase in plasma amylase, a tenfold increase in pancreatic MPO activity, and a threefold increase in interstitial space, and 90% of the acinar cells were abnormal. Prophylactic treatment with feG reduced the AP-induced plasma amylase activity by 45%, pancreatic MPO by 80%, the proportion of abnormal acinar cells by 30%, and interstitial space by 40%. Therapeutic treatment with feG significantly reduced the AP-induced abnormal acinar cells by 10% and the interstitial space by 20%. Pancreatic ICAM-1 mRNA expression was upregulated in AP and was reduced by 50% with prophylactic and therapeutic treatment with feG. We conclude that feG ameliorates experimental AP acting at least in part by modulating ICAM-1 expression in the pancreas.