New Pyrimidinone Bearing Aminomethylenes and Schiff Bases as Potent Antioxidant, Antibacterial, SARS-CoV-2, and COVID-19 Main Protease MPro Inhibitors: Design, Synthesis, Bioactivities, and Computational Studies.

New 2-thioxopyrimidinone derivatives (A1-A10) were synthesized in 87-96% yields via a simple three-component condensation reaction. These compounds were screened extensively through in vitro assays for antioxidant and antibacterial investigations. The DPPH assays resulted in the excellent potency of A6-A10 as antioxidants with IC50 values of 0.83 ± 0.125, 0.90 ± 0.77, 0.36 ± 0.063, 1.4 ± 0.07, and 1.18 ± 0.06 mg/mL, which were much better than 1.79 ± 0.045 mg/mL for the reference ascorbic acid. These compounds exhibited better antibacterial potency against Klebsiella with IC50 values of 2 ± 7, 1.32 ± 8.9, 1.19 ± 11, 1.1 ± 12, and 1.16 ± 11 mg/mL for A6-A10. High-throughput screenings (HTS) of these motifs were carried out including investigation of drug-like behaviors, physiochemical property evaluation, and structure-related studies involving DFT and metabolic transformation trends. The radical scavenging ability of the synthesized motifs was validated through molecular docking studies through ligand-protein binding against human inducible nitric oxide synthase (HINOS) PDB ID: 4NOS, and the results were promising. Furthermore, the antiviral capability of the compounds was examined by in silico studies using two viral proteins PDB ID: 6Y84 and PDB ID: 6LU7. Binding poses of ligands were discussed, and amino acids in the protein binding pockets were investigated, where the tested compounds showed much better binding affinities than the standard inhibitors, proving to be suitable leads for antiviral drug discovery. The stabilities of the molecular docked complexes in real systems were validated by molecular dynamics simulations.

Investigating the Impact of Cu2+ Doping on the Morphological, Structural, Optical, and Electrical Properties of CoFe2O4 Nanoparticles for Use in Electrical Devices.

This study investigated the production of Cu2+-doped CoFe2O4 nanoparticles (CFO NPs) using a facile sol-gel technique. The impact of Cu2+ doping on the lattice parameters, morphology, optical properties, and electrical properties of CFO NPs was investigated for applications in electrical devices. The XRD analysis revealed the formation of spinel-phased crystalline structures of the specimens with no impurity phases. The average grain size, lattice constant, cell volume, and porosity were measured in the range of 4.55-7.07 nm, 8.1770-8.1097 Å, 546.7414-533.3525 Å3, and 8.77-6.93%, respectively. The SEM analysis revealed a change in morphology of the specimens with a rise in Cu2+ content. The particles started gaining a defined shape and size with a rise in Cu2+ doping. The Cu0.12Co0.88Fe2O4 NPs revealed clear grain boundaries with the least agglomeration. The energy band gap declined from 3.98 eV to 3.21 eV with a shift in Cu2+ concentration from 0.4 to 0.12. The electrical studies showed that doping a trace amount of Cu2+ improved the electrical properties of the CFO NPs without producing any structural distortions. The conductivity of the Cu2+-doped CFO NPs increased from 6.66 × 10-10 to 5.26 × 10-6 ℧ cm-1 with a rise in Cu2+ concentration. The improved structural and electrical characteristics of the prepared Cu2+-doped CFO NPs made them a suitable candidate for electrical devices, diodes, and sensor technology applications.

Disseminated Cryptococcus in an immunocompetent patient due to prison yard pigeon exposure.

Opportunistic infection by Cryptococcus is one of the most common occurrences in patients with Human Immunodeficiency Virus (HIV) disease or Acquired Immunodeficiency Syndrome (AIDS); however, it is a very rare discovery in the immunocompetent. This encapsulated, aerobic fungus can be found in bird droppings, the soil, or on trees, and breathing the spores can lead to pneumonia, meningitis, sepsis, skin lesions, or disseminate throughout the body. We discuss the unique presentation of an immunocompetent former inmate who was admitted to the hospital due to symptoms of dyspnea and fever. After a thorough history, physical exam, and diagnostic testing, the patient was diagnosed with disseminated cryptococcosis. The patient has since made a complete recovery and was discharged home after receiving careful medical management.

Pharyngitis Workup Leads to the Discovery of Massive Tricuspid Vegetation.

Infective endocarditis (IE) is one of the leading causes of life-threatening infections and is most often observed among patients who use intravenous (IV) drugs. We discuss the unique presentation of a 31-year-old gentleman with a two-week history of sore throat and shortness of breath, who returned to his community emergency room with persistent symptoms of streptococcal pharyngitis. A thorough history, physical examination, and diagnostic workup were conducted, where a large, protruding, highly mobile vegetation was observed on echocardiogram. His blood cultures grew methicillin-resistant Staphylococcus aureus. A vegetation measuring over 5 cm was surgically removed from his tricuspid valve. Following the operation, he underwent six weeks of extensive in-patient medical management with IV antibiotics to treat IE. This patient made a complete recovery and has since returned home.

Syncope: An Atypical Presentation of Pulmonary Embolism Secondary to Occult Uterine Malignancy.

All syncopal patients who present to the emergency department should be considered for pulmonary embolism (PE) as part of their differential diagnosis. PE presenting as a syncopal episode and associated with occult uterine malignancy is uncommon. Review of the literature indicates that up to 10% of patients with unprovoked venous thromboembolism (VTE) are diagnosed with cancer in the year following that first episode of VTE. In patients suspected of having a PE who do not manifest any source of an embolism require eventual workup to screen for an occult malignancy. Here, we report a 74-year-old female who presented to the emergency department following an unexplained sudden loss of consciousness and eventually was found to have a massive saddle embolus caused by a uterine malignancy-induced VTE.

May-Thurner Syndrome Presenting as Acute Unexplained Deep Venous Thrombosis.

May-Thurner syndrome (MTS) is a rare cause of deep venous thrombosis and occurs due to an anatomic anomaly which produces chronic compression of the left common iliac vein by the overlying right common iliac artery when it passes between the right common iliac artery and the spine. Prolonged compression on the vein potentiates thrombus formation by impairing the intima and by leading to the development of membranes within the lumen that may decrease and/or block venous flow. In this case presentation, we elaborate on a case of a 43-year-old woman who presented with worsening left leg swelling and pain. The patient was diagnosed with MTS and underwent successful stent placement to relieve the compressed vein.

Methamphetamine-Induced Cardiomyopathy (MACM) in a Middle-Aged Man; a Case Report.

The development of methamphetamine-associated cardiomyopathy (MACM) represents a severe complication of chronic methamphetamine abuse. MACM-induced irreversible structural and functional changes in the heart can eventually lead to decompensated heart failure, ultimately requiring heart transplantation. In this case report we present a 47-year old male with a previous history of chronic amphetamine abuse who presented to the emergency room with severe dyspnea at rest associated with mild substernal non-radiating chest pain. He denied any previous cardiac history but had a positive urinary toxicology for methamphetamine. A complete cardiac workup ruled out all other etiologies. The patient required a 3-week intensive pharmacotherapy intervention to stabilize acute heart failure symptoms. At discharge he was classified as having New York Association Class III (NYHA-III) heart failure. His medical symptoms did not improve and he was considered for heart transplantation. With the increase in availability and abuse of methamphetamine, case of MACM such as ours are more frequently being encountered in the emergency departments. In addition to raising awareness, our case provides an outline of how MACM patients likely may present and the subsequent morbid sequela. Clinicians should maintain a high degree of suspicion when assessing all patients with a history of methamphetamine abuse. Early cardiac evaluation can help identify ventricular compromise in asymptomatic patients providing an opportunity to intervene prior to the development of irreversible MACM.