A direct correlation between brain iron and Alzheimer’s disease (AD) raises questions regarding the transport of non-transferrin-bound iron (NTBI), a toxic but less researched pool of circulating iron that is likely to increase due to pathological and/or iatrogenic systemic iron overload. Here, we compared the distribution of radiolabeled-NTBI (59Fe-NTBI) and transferrin-bound iron (59Fe-Tf) in mouse models of iron overload in the absence or presence of inflammation. Following a short pulse, most of the 59Fe-NTBI was taken up by the liver, followed by the kidney, pancreas, and heart. Notably, a strong signal of 59Fe-NTBI was detected in the brain ventricular system after 2 h, and the brain parenchyma after 24 h. 59Fe-Tf accumulated mainly in the femur and spleen, and was transported to the brain at a much slower rate than 59Fe-NTBI. In the kidney, 59Fe-NTBI was detected in the cortex after 2 h, and outer medulla after 24 hours. Most of the 59Fe-NTBI and 59Fe-Tf from the kidney was reabsorbed; negligible amount was excreted in the urine. Acute inflammation increased the uptake of 59Fe-NTBI by the kidney and brain from 2–24 hours. Chronic inflammation, on the other hand, resulted in sequestration of iron in the liver and kidney, reducing its transport to the brain. These observations provide direct evidence for the transport of NTBI to the brain, and reveal a complex interplay between inflammation and brain iron homeostasis. Further studies are necessary to determine whether transient increase in NTBI due to systemic iron overload is a risk factor for AD.

Converging observations from disparate lines of inquiry are beginning to clarify the cause of brain iron dyshomeostasis in sporadic Creutzfeldt-Jakob disease (sCJD), a neurodegenerative condition associated with the conversion of prion protein (PrPC), a plasma membrane glycoprotein, from α-helical to a β-sheet rich PrP-scrapie (PrPSc) isoform. Biochemical evidence indicates that PrPC facilitates cellular iron uptake by functioning as a membrane-bound ferrireductase (FR), an activity necessary for the transport of iron across biological membranes through metal transporters. An entirely different experimental approach reveals an evolutionary link between PrPC and the Zrt, Irt-like protein (ZIP) family, a group of proteins involved in the transport of zinc, iron, and manganese across the plasma membrane. Close physical proximity of PrPC with certain members of the ZIP family on the plasma membrane and increased uptake of extracellular iron by cells that co-express PrPC and ZIP14 suggest that PrPC functions as a FR partner for certain members of this family. The connection between PrPC and ZIP proteins therefore extends beyond common ancestry to that of functional cooperation. Here, we summarize evidence supporting the facilitative role of PrPC in cellular iron uptake, and implications of this activity on iron metabolism in sCJD brains.

Neonatal airway abnormalities are commonly encountered by the neonatologist, general pediatrician, maternal fetal medicine specialist, and otolaryngologist. This review article discusses common and rare anomalies that may be encountered, along with discussion of embryology, workup, and treatment. This article aims to provide a broad overview of neonatal airway anomalies to arm those caring for these children with a broad differential diagnosis and basic knowledge of how to manage basic and complex presentations.

Background Our study examined some of the social and medical factors associated with receiving pain palliation alone over more aggressive cytoreductive palliative measures, such as surgery, chemotherapy, or radiation among patients with head and neck cancer. Methods This retrospective study used the National Cancer Database 2016 for data analysis. Patient and tumor characteristics were examined using bivariate analysis and logistic regression to identify their association with receiving pain palliation alone versus cytoreductive palliation treatment. Results Using multivariate logistic regression analysis, insurance status (odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.15–0.50, p < 0.001), urbanity (OR: 1.73, 95%CI: 1.21–2.46, p = 0.002), and Charlson–Deyo scores greater than 3 (OR: 2.49, 95%CI: 1.38–4.47, p = 0.002) were significantly associated with receipt of pain palliation alone. Conclusions Clinicians should be aware of non‐health‐related factors, such as insurance status, that may influence patients' receipt of treatments in head and neck cancer.

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