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( ) is the world's most deadly infectious pathogen and new drugs are urgently required to combat the emergence of multi-(MDR) and extensively-(XDR) drug resistant strains. The bacterium specifically upregulates sterol uptake pathways in infected macrophages and the metabolism of host-derived cholesterol is essential for long-term survival Here, we report the development of antitubercular small molecules that inhibit the cholesterol oxidases CYP125 and CYP142, which catalyze the initial step of cholesterol metabolism. An efficient biophysical fragment screen was used to characterize the structure-activity relationships of CYP125 and CYP142, and identify a non-azole small molecule that can bind to the heme cofactor of both enzymes.
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Tuberculosis Diagnosis and Treatment Center, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
Background: Immune checkpoint inhibitors (ICIs) have emerged as the first-line treatment for driver-negative advanced non-small cell lung cancer (NSCLC). However, there is uncertainty regarding the availability and timing of ICI initiation in patients with NSCLC combined with pulmonary tuberculosis (TB). Additionally, the implementation of dual therapy for anti-TB and anti-tumor treatment poses significant challenges in terms of avoiding drug-drug interactions and reducing adverse reactions during clinical diagnosis and treatment.
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Department of Internal Medicine, Osmania Medical College, Hyderabad, IND.
Intramedullary spinal tuberculomas constitute a small percentage of spinal tuberculosis. These, in combination with brain tuberculomas, are an uncommon manifestation of central nervous system (CNS) tuberculosis. This report details a unique case of a 32-year-old retroviral disease-positive male who presented with a two-month history of symmetrical quadriparesis and recent seizures.
View Article and Find Full Text PDFTuberculous Subclavian Artery Pseudoaneurysm in a Young Male With Hemoptysis.
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Vascular Surgery, Unidade Local de Saúde São José, Lisbon, PRT.
Subclavian artery pseudoaneurysms (SAPs) are rare and most often secondary to trauma. On the contrary, a mycotic origin is exceedingly rare, and defining this etiology can become challenging. We present a rare case of a tuberculous SAP in a young patient.
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Maimonides Medical Center, Brooklyn, NY, USA.
An 85-year-old woman with a history of total knee replacements for osteoarthritis in the past, presented with left knee swelling and pain that persisted for 14 months. An initial diagnosis of synovial cyst was made, and she underwent multiple aspirations and symptomatic treatments without improvement. Repeat arthrocentesis showed a WBC of 56,000/μL with 61 % neutrophils and 34 % lymphocytes.
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