First-generation amperometric glucose biosensors incorporating alkanethiolate-protected gold nanoparticles, monolayer protected clusters (MPCs), within a xerogel matrix are investigated as model systems for nanomaterial-assisted electrochemical sensing strategies. The xerogel biosensors are comprised of platinum electrodes modified with composite films of (3-mercaptopropyl)trimethoxy silane xerogel embedded with glucose oxidase enzyme, doped with Au225(C6)75 MPCs, and coated with an outer polyurethane layer. Electrochemistry and scanning/transmission electron microscopy, including cross-sectional TEM, show sensor construction, humidity effects on xerogel structure, and successful incorporation of MPCs. Analytical performance of the biosensor scheme with and without MPC doping of the xerogel is determined from direct glucose injection during amperometry. MPC-doped xerogels yield significant enhancement of several sensor attributes compared to analogous films without nanoparticles: doubling of the linear range, sensitivity enhancement by an order of magnitude, and 4-fold faster response times accompany long-term stability and resistance to common interfering agents that are competitive with current glucose biosensing literature. Ligand chain length and the MPC/silane ratio studies suggest the MPC-induced enhancements are critically related to structure-function relationships, particularly those affecting interparticle electronic communication where the MPC network behaves as a three-dimensional extension of the working electrode into the xerogel film, reducing the system's dependence on diffusion and maximizing efficiency of the sensing mechanism. The integration of MPCs as a functional component of amperometric biosensor schemes has implications for future development of biosensors targeting clinically relevant species.

Background Little is known about the relationships between SARS-CoV-2, the respiratory virus responsible for the ongoing COVID-19 pandemic, and the upper respiratory tract (URT) microbiome. Objective Our objectives were 1) to compare the URT microbiome between SARS-CoV-2-infected and -uninfected adults, and 2) to examine the association of SARS-CoV-2 viral load with the URT microbiome during COVID-19. Methods We characterized the URT microbiome using 16S ribosomal RNA sequencing in 59 adults (38 with confirmed, symptomatic, mild-to-moderate COVID-19 and 21 asymptomatic, uninfected controls). In those with COVID-19, we measured SARS-CoV-2 viral load using quantitative reverse transcription PCR. We then examined the association of SARS-CoV-2 infection status and its viral load with the ⍺-diversity, β-diversity, and abundance of bacterial taxa of the URT microbiome. Our main models were all adjusted for age and sex. Results The observed species index was significantly higher in SARS-CoV-2-infected than in -uninfected adults (β linear regression coefficient=7.53, 95%CI=0.17-14.89, p =0.045). In differential abundance testing, 9 amplicon sequence variants (ASVs) were significantly different in both of our comparisons, with Peptoniphilus lacrimalis , Campylobacter hominis , Prevotella 9 copri , and an Anaerococcus unclassified ASV being more abundant in those with SARS-CoV-2 infection and in those with high viral load during COVID-19, whereas Corynebacterium unclassified, Staphylococcus haemolyticus , Prevotella disiens , and 2 Corynebacterium_1 unclassified ASVs were more abundant in those without SARS-CoV-2 infection and in those with low viral load during COVID-19. Conclusion Our findings suggest complex associations between SARS-CoV-2 and the URT microbiome in adults. Future studies are needed to examine how these viral-bacterial interactions can impact the clinical progression, severity, and recovery of COVID-19.

How to Cite this Article Kimura KS Freeman MH Wessinger BC et al Interim analysis of an open-label randomized controlled trial evaluating nasal irrigations in non-hospitalized patients with coronavirus disease Int Forum Allergy Rhinol-Response to the coronavirus disease 2019 (COVID-19) pandemic has primarily focused on pharmacologic and medical interventions, including antivirals, 1 convalescent sera, 2 and vaccinations, 3 with each potentially critical in the fight against COVID-19, particularly among high-risk and hospitalized populations. Non-hospitalized patients with mild to moderate disease comprise an estimated 81% of those affected with COVID-19, 4 and there are currently no widely available interventions with proven ability to hasten symptom resolution or reduce viral shedding. We started an open-label randomized controlled trial (RCT) to evaluate the effect of nasal irrigation with hypertonic saline (HTS) or saline with surfactant on upper respiratory symptoms and viral load. Viral shedding is highest in the nasal

Ototoxic side effects of cisplatin and aminoglycosides have been extensively studied, but no therapy is available to date. Sensory hair cells, upon exposure to cisplatin or aminoglycosides, undergo apoptotic and necrotic cell death. Blocking these cell death pathways has therapeutic potential in theory, but incomplete protection and lack of therapeutic targets in the case of necrosis, has hampered the development of clinically applicable drugs. Over the past decade, a novel form of necrosis, termed necroptosis, was established as an alternative cell death pathway. Necroptosis is distinguished from passive necrotic cell death, in that it follows a cellular program, involving the receptor-interacting protein kinase (RIPK) 1 and RIPK3. In this study, we used pharmacological and genetic interventions in the mouse to test the relative contributions of necroptosis and caspase-8-mediated apoptosis toward cisplatin and aminoglycoside ototoxicity. We find that ex vivo, only apoptosis contributes to cisplatin and aminoglycoside ototoxicity, while in vivo, necroptosis as well as apoptosis are involved in both sexes. Inhibition of necroptosis and apoptosis using pharmacological compounds is thus a viable strategy to ameliorate aminoglycoside and cisplatin ototoxicity.

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BackgroundThe upper respiratory tract (URT) is the portal of entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-CoV-2 likely interacts with the URT microbiome. However, understanding of the associations between the URT microbiome and the severity of coronavirus disease 2019 (COVID-19) is still limited.ObjectiveOur primary objective was to identify URT microbiome signature/s that consistently changed over a spectrum of COVID-19 severity.MethodsUsing data from 103 adult participants from two cities in the United States, we compared the bacterial load and the URT microbiome between five groups: 20 asymptomatic SARS-CoV-2-negative participants, 27 participants with mild COVID-19, 28 participants with moderate COVID-19, 15 hospitalized patients with severe COVID-19, and 13 hospitalized patients in the ICU with very severe COVID-19.ResultsURT bacterial load, bacterial richness, and within-group microbiome composition dissimilarity consistently increased as COVID-19 severity increased, while the relative abundance of an amplicon sequence variant (ASV), Corynebacterium_unclassified.ASV0002, consistently decreased as COVID-19 severity increased.ConclusionsWe observed that the URT microbiome composition significantly changed as COVID-19 severity increased. The URT microbiome could potentially predict which patients may be more likely to progress to severe disease or be modified to decrease severity. However, further research in additional longitudinal cohorts is needed to better understand how the microbiome affects COVID-19 severity.

Objective To characterize the incidence of sigmoid sinus occlusion (SSO) following translabyrinthine (TL) surgery for posterior fossa tumor resection and determine the association with cerebrospinal fluid (CSF) leak. Study Design Retrospective case series. Setting Tertiary referral center. Methods Patients undergoing TL surgery for vestibular schwannoma from 2012 to 2020 were included. Demographic data, medical history, preoperative tumor length and volume, and postoperative complications including CSF leak were recorded. Neuroradiology review of postoperative magnetic resonance imaging was used to determine the presence or absence of flow through the sigmoid sinus. Results Of 205 patients undergoing TL, 21 (10.2%) experienced CSF leak postoperatively. Overall 56 (27%) demonstrated SSO on immediate postoperative magnetic resonance imaging. CSF leaks were more likely in those with SSO (19.6%) than those without SSO (6.7%; odds ratio, 3.54 [95% CI, 1.25-10.17]). Tumor volume and body mass index were not significantly associated with CSF leak. In total, 105 (51%) patients had some degree of sigmoid sinus thrombosis, but nonocclusive thrombosis was not associated with CSF leak. Conclusion SSO after TL approaches is common and appears to be significantly associated with postoperative CSF leak development. Minimizing manipulation of the sigmoid sinus during TL surgery and compression after surgery may have a role in preventing CSF leak.

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