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The two polar clinical forms of leprosy, termed tuberculoid and lepromatous, have polarized cellular immune responses with complex immunological distinctions. The predominance of DCs in tuberculoid leprosy has been reported, while the lepromatous pattern of illness is associated with weak activation of local populations of DCs. TiO2 nanoparticles have previously been shown to induce maturation of these cells, leading to an inflammatory response similar to adjuvant usage in vaccine administration. We aimed to evaluate the effect of potassium-incorporated Ti oxide nanostructures, namely KTiOxs, in the response of human monocyte-derived DCs to live M. leprae. Human monocytic cell line dual THP-1, which harbors two inducible reporter plasmid systems for transcription factor activation of NF-κB and interferon regulating factor (IRF), was treated with titanium control or with 1 mol/L KOH-treated Ti or 10 mol/L KOH for 24 h. Subsequently, cells were infected with M. leprae. KTiOx nanoparticles increase DC phagocytic activity without inflammation. KTiOx exposure of DCs led to an increase in IRF activation with modulation of the inflammatory response to live M. leprae. It also led to differential secretion of the critical components of innate immune response and the development of cell-mediated immunity against intracellular pathogens. This study demonstrates the effect of nanostructures of KTiOxs and the usefulness of nanoparticle technology in the in vitro activation of human DCs against an infectious disease with a puzzling immune spectrum. Our findings may prompt future therapeutic strategies, such as DC immunotherapy for disseminated and progressive lepromatous lesions.

Immune-mediated necrotizing myopathy (IMNM) is a subtype of inflammatory myopathy that is characterized by proximal muscle weakness, markedly elevated serum creatine kinase, myopathic electromyographic findings, and muscle biopsies revealing necrosis or regeneration with sparse inflammatory infiltrate. IMNM tends to be idiopathic but has been associated with certain medications. This supports the possibility for other pharmacotherapies to induce IMNM—particularly leflunomide. Leflunomide is used in the treatment for rheumatoid arthritis and has been shown to induce autoimmune diseases—including autoimmune hepatitis and polymyositis. After an extensive review of history and workup of muscle weakness, we conclude that leflunomide induced an IMNM in our patient. As this is the first case of leflunomide-induced IMNM, it is important for clinicians to suspect an inflammatory myopathy in the setting of myositis while on leflunomide.

Combined central retinal artery and vein occlusion (CCRAVO) is a rare entity characterized by features of tortuous retinal veins, retinal hemorrhage, optic disk edema and pallor, macula edema, cherry-red spot, and cotton-wool spots. The occurrence of CCRAVO in the adult population is often in the setting of systemic disease; while CCRAVO in the pediatric population is frequently associated with infection of the sinuses, preseptal cellulitis, or orbital cellulitis. It has been hypothesized that CCRAVO can result from methicillin-resistant Staphylococcus aureus (MRSA) sepsis-induced coagulation disturbances, orbital cellulitis, and even orbital compartment syndrome; however, there are insufficient reports of this complication. This case report sheds light on one such case with irreversible vision loss as a sequela.

Combined central retinal artery and vein occlusion (CCRAVO) is a rare entity characterized by features of tortuous retinal veins, retinal hemorrhage, optic disk edema and pallor, macula edema, cherry-red spot, and cotton-wool spots. The occurrence of CCRAVO in the adult population is often in the setting of systemic disease; while CCRAVO in the pediatric population is frequently associated with infection of the sinuses, preseptal cellulitis, or orbital cellulitis. It has been hypothesized that CCRAVO can result from methicillin-resistant Staphylococcus aureus (MRSA) sepsis-induced coagulation disturbances, orbital cellulitis, and even orbital compartment syndrome; however, there are insufficient reports of this complication. This case report sheds light on one such case with irreversible vision loss as a sequela.

Isogenic cells can manifest distinct cellular fates for a single stress, however the nongenetic mechanisms driving such fates remain poorly understood. Here, we implement a robust multi-channel live-cell imaging approach to uncover noncanonical factors governing cell fate. We show that in response to acute glucose removal (AGR), budding yeast undergo distinct fates becoming either quiescent or senescent. Senescent cells fail to resume mitotic cycles following glucose replenishment but remain responsive to nutrient stimuli. Whereas quiescent cells manifest starvation-induced adaptation, senescent cells display perturbed endomembrane trafficking and defective nucleus-vacuole junction (NVJ) expansion. Surprisingly, we also show senescence occurs in the absence of lipid droplets. Importantly, we identify the nutrient-sensing linked kinase Rim15 as a key biomarker that predicts cell fates before AGR stress. We propose that isogenic yeast challenged with acute nutrient shortage contain determinants that influence their post-stress fate, and demonstrate that specific nutrient signaling, stress-response, endomembrane trafficking, and inter-organelle tether biomarkers are early indicators for long-term fate outcomes. Competing Interest Statement The authors have declared no competing interest.