Clinical characteristics of patients diagnosed with bilateral sudden sensorineural hearing loss.

This study investigated the etiology, clinical features, and prognosis of patients diagnosed with bilateral sudden sensorineural hearing loss (BSSNHL). The clinical data of 100 patients with bilateral sudden hearing loss as a chief complaint treated at Xiangya Second Hospital of Central South University between January 2010 and August 2022, including clinical characteristics, audiometric data, and prognosis, were retrospectively analyzed. These 100 cases accounted for 8.09% (100/1235) of all patients admitted for sudden sensorineural hearing loss (SSNHL) during the same period. Of these, 71 were simultaneous cases and 29 were sequential cases of BSSNHL. Among the 200 ears analyzed in this study, 13, 36, 57, and 94 had mild, moderate, severe, and profound sensorineural hearing loss, respectively. The overall effective rate after comprehensive treatment was 32%, with significant differences in efficacy and prognosis among different degrees of hearing loss (p < 0.05). Comorbidities of hypertension (24 cases), diabetes (14 cases), and coronary heart disease (9 cases) significantly impacted therapeutic efficacy and prognosis in patients with BSSNHL (p < 0.05). Compared to unilateral SSNHL, BSSNHL exhibits distinctive characteristics.

N6-methyladenosine methylation analysis of circRNAs in acquired middle ear cholesteatoma.

Introduction: Middle ear cholesteatoma is a chronic middle ear disease characterized by severe hearing loss and adjacent bone erosion, resulting in numerous complications. This study sought to identify pathways involved in N6-methyladenosine (m6A) modification of circRNA in middle ear cholesteatoma. Methods: A m6A circRNA epitranscriptomic microarray analysis was performed in middle ear cholesteatoma tissues (n = 5) and normal post-auricular skin samples (n = 5). Bioinformatics analyses subsequently explored the biological functions (Gene Ontology, GO) and signaling pathways (Kyoto Encyclopedia of Genes and Genomes, KEGG) underlying middle ear cholesteatoma pathogenesis. Methylated RNA immunoprecipitation qPCR (MeRIP-qPCR) was performed to verify the presence of circRNAs with m6A modifications in middle ear cholesteatoma and normal skin samples. Results: Microarray analysis identified 3,755 circRNAs as significantly differentially modified by m6A methylation in middle ear cholesteatoma compared with the normal post-auricular skin. Among these, 3,742 were hypermethylated (FC ≥ 2, FDR < 0.05) and 13 were hypomethylated (FC ≤ 1/2, FDR < 0.05). GO analysis terms with the highest enrichment score were localization, cytoplasm, and ATP-dependent activity for biological processes, cellular components, and molecular functions respectively. Of the eight hypermethylated circRNA pathways, RNA degradation pathway has the highest enrichment score. Peroxisome Proliferator-Activated Receptor (PPAR) signaling pathway was hypomethylated. To validate the microarray analysis, we conducted MeRIP-qPCR to assess the methylation levels of five specific m6A-modified circRNAs: hsa_circRNA_061554, hsa_circRNA_001454, hsa_circRNA_031526, hsa_circRNA_100833, and hsa_circRNA_022382. The validation was highly consistent with the findings from the microarray analysis. Conclusion: Our study firstly presents m6A modification patterns of circRNAs in middle ear cholesteatoma. This finding suggests a direction for circRNA m6A modification research in the etiology of cholesteatoma and provides potential therapeutic targets for the treatment of middle ear cholesteatoma.

Current progress towards prevention of Nipah and Hendra disease in humans: A scoping review of vaccine and monoclonal antibody candidates being evaluated in clinical trials.

OBJECTIVES: Nipah and Hendra are deadly zoonotic diseases with pandemic potential. To date, no human vaccine or monoclonal antibody (mAb) has been licensed to prevent disease caused by these pathogens. The aim of this scoping review was to identify and describe all Phase I, II, and III clinical trials of vaccine candidates or mAbs candidates designed to prevent Nipah and Hendra in humans and to compare the characteristics of the vaccine candidates to characteristics outlined in the Target Product Profile drafted by the World Health Organisation as part of the WHO Research & Development Blueprint for Action to Prevent Epidemics. METHODS: We searched 23 clinical trial registries, the Cochrane Central Register of Clinical Trials, and grey literature up to June 2023 to identify vaccine and mAb candidates being evaluated in registered clinical trials. Vaccine candidate and trial characteristics were double-extracted for evaluation and the vaccine candidate characteristics were compared with the preferred and critical criteria of the World Health Organisation's Target Product Profile for Nipah virus vaccine. RESULTS: Three vaccine candidates (Hendra Virus Soluble Glycoprotein Vaccine [HeV-sG-V], PHV02, and mRNA-1215) and one mAb (m102.4) had a registered human clinical trial by June 2023. All trials were phase 1, dose-ranging trials taking place in the United States of America or Australia and enrolling healthy adults. Although all vaccine candidates meet the dose regimen and route of administration criteria of the Target Product Profile, other criteria such as measures of efficacy and reactogenicity will need to be evaluated in the future as evidence becomes available. CONCLUSION: Multiple vaccine candidates and one mAb candidate have reached the stage of human clinical trials and are reviewed here. Monitoring progress during evaluation of these candidates and candidates entering clinical trials in the future can help highlight many of the challenges that remain.

Access to Burn Care in the US.

This cross-sectional study examines burn incidence rates and accessibility of American Burn Association­verified or self-designated burn centers from 2013 to 2019.

Natural Products Lysobactin and Sorangicin A Show In Vitro Activity against Mycobacterium abscessus Complex.

The prevalence of lung disease caused by Mycobacterium abscessus is increasing among patients with cystic fibrosis. M. abscessus is a multidrug resistant opportunistic pathogen that is notoriously difficult to treat due to a lack of efficacious therapeutic regimens. Currently, there are no standard regimens, and treatment guidelines are based empirically on drug susceptibility testing. Thus, novel antibiotics are required. Natural products represent a vast pool of biologically active compounds that have a history of being a good source of antibiotics. Here, we screened a library of 517 natural products purified from fermentations of various bacteria, fungi, and plants against M. abscessus ATCC 19977. Lysobactin and sorangicin A were active against the M. abscessus complex and drug resistant clinical isolates. These natural products merit further consideration to be included in the M. abscessus drug pipeline. IMPORTANCE The many thousands of people living with cystic fibrosis are at a greater risk of developing a chronic lung infection caused by Mycobacterium abscessus. Since M. abscessus is clinically resistant to most anti-TB drugs available, treatment options are limited to macrolides. Despite macrolide-based therapies, cure rates for M. abscessus lung infections are 50%. Using an in-house library of curated natural products, we identified lysobactin and sorangicin A as novel scaffolds for the future development of antimicrobials for patients with M. abscessus infections.

The Use of Panitumumab-IRDye800CW in a Novel Murine Model for Conjunctival Squamous Cell Carcinoma.

Purpose: Conjunctival squamous cell carcinoma (SCC) is a sight-threatening ocular surface malignancy with the primary treatment modality being surgical resection. To evaluate surgical imaging modalities to improve surgical resection, we established a novel murine model for conjunctival SCC to demonstrate the utility of panitumumab-IRDye800, a fluorescently labeled anti-epidermal growth factor receptor (EGFR) antibody. Methods: NOD-scid IL2Rgammanull (NSG) mice received subconjunctival injection of UM-SCC-1 or SCC-9, head and neck SCC cell lines. On tumor growth, mice were injected with Panitumumab-IRDye800CW, and imaged with a small animal imaging system and optical coherence tomography (OCT). Immunohistochemistry for SCC markers were used to confirm tumor origin. Results: Seventy-five percent (N = 4) of the UM-SCC-1 group developed aggressive, rapidly growing tumors that were P40 and EGFR positive within two weeks of inoculation. The SCC-9 tumors failed to demonstrate any growth (N = 4). Ocular tumors demonstrated high fluorescence levels with a tumor to background ratio of 3.8. Conclusions: Subconjunctival injections are an appropriate technique to create in vivo models for assessing treatment modalities and novel therapies in conjunctival SCC. Translational Relevance: This model demonstrates Panitumumab-IRDye800CW's utility in the ophthalmic setting and suggests that clinical trials may be warranted.

The Health Impact Fund: making the case for engagement with pharmaceutical laboratories in Brazil, Russia, India, and China.

Despite progress in global health, the general disease burden still disproportionately falls on low- and middle-income countries. The health needs of these countries' populations are unmet because there is a shortage in drug research and development, as well as a lack of access to essential drugs. This health disparity is especially problematic for diseases associated with poverty, namely neglected tropical diseases and microbial infections. Currently, the pharmaceutical landscape focuses on innovations determined by profit margins and intellectual property protection. To expand drug accessibility and catalyze research and development for neglected diseases, a team of researchers proposed the Health Impact Fund as a potential solution. However, the fund is predominantly considering partnerships with pharmaceutical giants in high-income countries. This commentary explores the limitations and benefits in partnering with pharmaceutical companies based in Brazil, Russia, India, and China (BRIC), with the goal of expanding the Health Impact Fund's vision to incorporate long-term, local partnerships. Identified limitations to a BRIC country partnership include lower levels of drug development expertise compared to their high-income pharmaceutical counterparts, and whether the Health Impact Fund and the participating stakeholders have the financial capability to assist in bringing a new drug to market. However, potential benefits include the creation of new incentives to fuel competitive local innovation, more equitable routes to drug discovery and development, and a product pipeline that could involve stakeholders in lower- and middle-income countries. Our commentary explores how partnership with pharmaceutical firms in BRIC countries might be advantageous for all: The Health Impact Fund, pharmaceutical companies in BRIC economies, and stakeholders in low- and middle- income countries.

Development of High-Throughput Methods for Sodium-Ion Battery Cathodes.

Combinatorial synthesis of Li-ion batteries has proven extremely powerful in screening complex compositional spaces for next-generation materials. To date, no Na-ion counterpart exists wherein Na-ion cathodes can be synthesized in such a way to be comparable to that obtained in bulk synthesis. Herein, we develop a synthesis route wherein hundreds of milligram-scale powder samples can be made in a total time of 3 days. We focus on materials in the Na-Fe-Mn-O pseudoternary system of high immediate interest. Using a sol-gel method, developed herein, yields both phase-pure combinatorial samples of Na2/3Fe1/2Mn1/2O2 and NaFe1/2Mn1/2O2, consistent with previous reports on bulk samples of interest commercially. By contrast, the synthesis route used for Li-ion cathodes (namely coprecipitations) does not yield phase pure materials, suggesting that the sol-gel method is more effective in mixing the Na, Fe, and Mn than coprecipitation. This has important consequences for all attempts to make these materials, even in bulk. Finally, we demonstrate that these milligram-scale powder samples can be tested electrochemically in a combinatorial cell. The resulting cyclic voltammograms are in excellent agreement with those found on bulk samples in the literature. This demonstrates that the methodology developed here will be effective in characterizing the hundreds of samples needed to understand the complex ternary systems of interest and that such results will scale-up well to the gram and kilogram scale.