Methicillin-Resistant Staphylococcus aureus Sepsis and Orbital Cellulitis Leading to a Combined Central Retinal Artery and Vein Occlusion: A Case Report.

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.

Leflunomide-Induced Immune-Mediated Necrotizing Myopathy in a Patient With Rheumatoid Arthritis: A Case Report.

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.

Nutrient Signaling, Stress Response, and Inter-organelle Communication Are Non-canonical Determinants of Cell Fate.

Isogenic cells 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 undergoes 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, senescence occurs even in the absence of lipid droplets. Importantly, we identify the nutrient-sensing kinase Rim15 as a key biomarker predicting cell fates before AGR stress. We propose that isogenic yeast challenged with acute nutrient shortage contains determinants influencing post-stress fate and demonstrate that specific nutrient signaling, stress response, trafficking, and inter-organelle biomarkers are early indicators for long-term fate outcomes.

IL-26 mediated human cell activation and antimicrobial activity against Borrelia burgdorferi.

Lyme disease is an inflammatory disease caused by infection with Borrelia burgdorferi (Bb). Inflammatory sequelae of Bb infection appear to be refractory to antibiotics. An antimicrobial peptide with the ability to bind the DNA in the tissue could serve as a viable option of treatment for chronic complications of Lyme borreliosis. DNA of Bb can remain in tissues causing a prolonged inflammatory response that lead to chronic joint pain. Here we examined the effect of IL-26, a newly reported antimicrobial protein, against Bb DNA. An antimicrobial effect of IL-26 on the spirochete was observed. In human macrophages, IL-26 treated cells showed an increase in IRF activation upon Bb stimulation. Moreover, IL-26 treated macrophages showed an increased in phagocytic activity compared to untreated cells. Although no Bb DNA degradation was observed using a TUNEL assay run in an agarose gel, a Comet assay on whole bacteria showed cellular and Bb DNA degradation by IL-26. Our results showed that IL-26 (monomer and dimer) has not only the potential to control Bb growth in vitro, but it also enhances the anti-borrelial response of human macrophages. Further research aiming to characterize the role of IL-26 in controlling other aspects of the inflammatory response that could provide insight of its potential therapeutic applications are needed.

Integration of Multiple Metabolic Signals Determines Cell Fate Prior to Commitment.

Cell-fate decisions are central to the survival and development of both uni- and multicellular organisms. It remains unclear when and to what degree cells can decide on future fates prior to commitment. This uncertainty stems from experimental and theoretical limitations in measuring and integrating multiple signals at the single-cell level during a decision process. Here, we combine six-color live-cell imaging with the Bayesian method of statistical evidence to study the meiosis/quiescence decision in budding yeast. Integration of multiple upstream metabolic signals predicts individual cell fates with high probability well before commitment. Cells "decide" their fates before birth, well before the activation of pathways characteristic of downstream cell fates. This decision, which remains stable through several cell cycles, occurs when multiple metabolic parameters simultaneously cross cell-fate-specific thresholds. Taken together, our results show that cells can decide their future fates long before commitment mechanisms are activated.