Glioblastoma (GBM) is the most frequent and inevitably lethal primary brain cancer in adults. It is recognized that the overexpression of the endosomal Na+/H+ exchanger NHE9 is a potent driver of GBM progression. Patients with NHE9 overexpression have a threefold lower median survival relative to GBM patients with normal NHE9 expression, using available treatment options. New treatment strategies tailored for this GBM subset are much needed. According to the prevailing model, NHE9 overexpression leads to an increase in plasma membrane density of epidermal growth factor receptors (EGFRs) which consequently enhances GBM cell proliferation and migration. However, this increase is not specific to EGFRs. In fact, the hallmark of NHE9 overexpression is a pan‐specific increase in plasma membrane receptors. Paradoxically, we report that this gain of function in NHE9 can be exploited to effectively target GBM cells for destruction. When exposed to gold nanoparticles, NHE9 overexpressing GBM cells accumulated drastically high amounts of gold via receptor‐mediated endocytosis, relative to control. Irradiation of these cells with near‐infrared light led to apoptotic tumour cell death. A major limitation for delivering therapeutics to GBM cells is the blood‐brain barrier (BBB). Here, we demonstrate that macrophages loaded with gold nanoparticles can cross the BBB, deliver the gold nanoparticles and effect the demise of GBM cells. In combination with receptor tyrosine kinase inhibition, we show this approach holds great promise for a new GBM‐targeted therapy.

Author contributionsNE performed tissue isolation, whole mount preparation and imaging/analysis, and ECG recordings. RRM performed intracardiac recordings, ECG recordings, patch clamp electrophysiology, and analysis of echocardiography and provided mentoring support to NE. SH and CS performed RNA isolations and qPCR experiments and analyses. SW performed cardiac myocyte isolation, picrosirius red staining, imaging, and analysis, and qPCR and analysis. AAB performed the RNA isolation for RNA-Seq. CC performed picrosirius red staining and analysis. LJ and WRA contributed to whole mount image analysis. SN mentored and trained NE in whole mount preparation and imaging analysis. NRM and MSR provided mentorship and funding to RRM. LLI contributed to experimental design and interpretation and provided funding. LFLS provided mentoring and training to NE. NE, RRM, LFLS, and LLI cowrote the manuscript. NE and RRM are recognized as co-first authors. NE and RRM performed equal amounts of work and so their authorship is listed in alphabetical order.

Purpose The aim of the study was to investigate whether olfactory fluctuations (OF) are pronounced in patients with sinonasal olfactory dysfunction (OD). Methods The retrospective investigation included patients aged 18 years or older, who consulted a tertiary referral center for olfactory loss. Patients with normal smell function were excluded. Patients answered a structured questionnaire about their olfactory symptoms, with specific questions related to the presence of OF and its average frequency, amplitude, duration, time since most recent OF, and associated symptoms of self-reported OF. Patients also underwent clinical evaluation including a structured medical history and physical examination including nasal endoscopy. In addition, we assessed orthonasal olfactory function using Sniffin’ Sticks, and gustatory function using “taste sprays”. Results Participants included 131 men and 205 women (n = 336), aged 18 to 86 years (mean 50, SD 16). Patient-reported fluctuations occurred most frequently in sinonasal (38%), idiopathic (29%), and postviral (29%) OD. Amplitude of OF was highest in postviral OD (p = 0.009). Average frequency, duration, and the time since the most recent fluctuation were not significantly different between groups (all p’s > 0.42). Odor discrimination (p = 0.002) and identification (p = 0.017) scores were higher among those individuals with OF. Conclusion Amplitude of OF may help distinguish postviral from other causes of OD, especially in patients presenting with equivocal symptoms of sinonasal disease.

PURPOSE: Despite faster healing and reduced risk of rejection, some surgeons are hesitant to adopt Descemet membrane endothelial keratoplasty (DMEK) due to difficult intraoperative tissue preparation. Use of eye bank prestripped, prestained, and preloaded (p 3 ) DMEK tissue can reduce the learning curve and risk of complications. MATERIALS AND METHODS: We conducted a prospective study including 167 eyes undergoing p 3 DMEK and compared outcomes to a retrospective chart review of 201 eyes that underwent standard DMEK surgery. The primary outcomes were graft failure, detachment, and re-bubbling frequency. The secondary outcomes included baseline and postoperative visual acuity at months 1, 3, 6, and 12. Baseline and postoperative central corneal thickness (CCT) and endothelial cell counts (ECC) were collected. RESULTS: ECC decrease for p 3 DMEK at 3, 6, and 12 months were 15.0%, 18.0%, and 21.0%, respectively. Forty (24%) of p 3 DMEK and 72 (35.8%) of standard DMEK eyes had at least a partial graft detachment. There was no difference in CCT, graft failures, or re-bubble frequency. At 6 months, mean visual acuity was 20/26 and 20/24 for standard and p 3 DMEK, respectively. Mean case time for p 3 DMEK with phaco or p 3 DMEK alone was 33 and 24 min, respectively. Mean case time for eyes undergoing DMEK with phaco or DMEK alone was 59 and 45 min, respectively. CONCLUSION: P 3 DMEK tissue is safe and can provide excellent clinical outcomes that are comparable to standard DMEK tissue. Eyes undergoing p 3 DMEK may have lower graft detachment and ECC loss.