Junctional Modulation of Round Window Membrane Enhances Dexamethasone Uptake into the Inner Ear and Recovery after NIHL

Delivery of substances into the inner ear via local routes is increasingly being used in clinical treatment. Studies have focused on methods to increase permeability through the round window membrane (RWM) and enhance drug diffusion into the inner ear. However, the clinical applications of those methods have been unclear and few studies have investigated the efficacy of methods in an inner ear injury model. Here, we employed the medium chain fatty acid caprate, a biologically safe, clinically applicable substance, to modulate tight junctions of the RWM. Intratympanic treatment of sodium caprate (SC) induced transient, but wider, gaps in intercellular spaces of the RWM epithelial layer and enhanced the perilymph and cochlear concentrations/uptake of dexamethasone. Importantly, dexamethasone co–administered with SC led to significantly more rapid recovery from noise–induced hearing loss at 4 and 8 kHz, compared with the dexamethasone-only group. Taken together, our data indicate that junctional modulation of the RWM by SC enhances dexamethasone uptake into the inner ear, thereby hastening the recovery of hearing sensitivity after noise trauma.

Glycolytic Metabolism Is Critical for the Innate Antibacterial Defense in Acute Streptococcus pneumoniae Otitis Media

ObjectiveStreptococcus pneumoniae (S.pn) is a common respiratory pathogen and a frequent cause of acute otitis media (AOM) in children. However, little is known about the immunometabolism during AOM. This study was to assess the presence of glucose metabolic reprogramming during AOM and its underlying mechanism affecting inflammatory response and middle ear injury.MethodsThe levels of glycolytic metabolism were evaluated by measuring the expression of glycolysis-related genes and the production of metabolites. HE stain, immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and Western blot were performed to measure the effect of glucose metabolic reprogramming on inflammatory response, pneumococcal clearance, hypoxia-inducible factor 1 alpha (HIF-1α) expression and cytokine secretion during AOM, respectively.ResultsThe analysis of microarray revealed an increase of the expression of glycolysis-related genes during S.pn–induced AOM, which was verified by real-time PCR. Increased glycolysis promoted the production of IL-1β and TNF-α and facilitated the clearance of S.pn by enhancing phagocytosis and killing capability of neutrophils, but also aggravated the middle ear injury. Furthermore, these pathogenic effects could be reversed after glycolytic inhibitor 2DG treatment. Additionally, HIF-1α was observed to involve in glycolytic metabolism during AOM.ConclusionS.pn infection induced increased glycolysis conversion during AOM, which promoted inflammatory responses and bacterial clearance, but also aggravated tissue damage.

HEARING LOSS IN BLAST TRAUMA VICTIMS. A MULTICENTRE RETROSPECTIVE STUDY

Objective: To describe the resultant Otologic morbidity and report on the early outcomes following blasts occurring in twin cities of Quetta and Peshawar. Study Design: Case series. Place and Duration of Study: ENT department Tertiary Care Centre Quetta and Tertiary Care Hospital Peshawar. Study period was, from Jan 2013 to Dec 2013. Methodology: All bomb blast patients brought to the hospitals were included in study. Participants completed Symptom Assessment Forms followed by detailed ENT examination and Pure Tone Audiograms on arrival and after 6 weeks. Results: A total of 504 patients were included initially of which 80% of the patients were male. About 57.8% of the patients complained of ear injury, 21.6% of the total patients had tympanic membrane perforation on initial presentation. Chances of spontaneous closure of perforation were 20.9% in our study. Chances of hearing improvement were 17.9% in our study at the end of the study period. Conclusion: Blast related otologic injuries constituted a major source of morbidity The most common type of hearing loss following a blast trauma was mild to moderate conductive type. Chances of recovery of hearing following blast do exist (17.9%). Suspected patients should be regularly assessed and followed up. Much work needs to be done to study the impact of blast trauma on hearing in our country.

FBXO3 Downregulation Attenuates Noise-induced Hearing Loss by Suppressing ATG10 Degradation and Activating Autophagy

Noise induced hearing loss (NIHL) is a kind of hearing impairment, which is next to the age-related hearing loss. More and more evidences have verified that overproduction of reactive oxygen species is a common pathologic phenomenon of different inner ear injury including NIHL, and autophagy contributes to attenuate NIHL by reducing oxidative stress. However, the underlying mechanism by which noise exposure causes autophagy activation remains unclear. In this study, we found that NIHL was accompanied by autophagy in the rat cochlea. Furthermore, twelve common genes were found at the GEO datasets GSE85290 and GSE8342, and E3 ubiquitination ligase FBXO3 was confirmed significantly reduced in NIHL rat cochlea. Next, we demonstrated that FBXO3 can directly binding with autophagy-related protein 10 (ATG10), which is necessary for the initiation of autophagy, and mediate its degradation. In vivo animal model treatment with rapamycin, an autophagy activator, significantly reduced the NIHL. Based on these data, we confirmed that FBXO3 played an important role in autophagy caused by NIHL, may be a potential target of NIHL treatment.

Allocation of funding into blast injury-related research and blast traumatic brain injury between 2000 and 2019: analysis of global investments from public and philanthropic funders

IntroductionThere is little systematic tracking or detailed analysis of investments in research and development for blast injury to support decision-making around research future funding.MethodsThis study examined global investments into blast injury-related research from public and philanthropic funders across 2000–2019. Research databases were searched using keywords, and open data were extracted from funder websites. Data collected included study title, abstract, award amount, funder and year. Individual awards were categorised to compare amounts invested into different blast injuries, the scientific approaches taken and analysis of research investment into blast traumatic brain injury (TBI).ResultsA total of 806 awards were identified into blast injury-related research globally, equating to US$902.1 million (m, £565.9m GBP). There was a general increase in year-on-year investment between 2003 and 2009 followed by a consistent decline in annual funding since 2010. Pre-clinical research received $671.3 m (74.4%) of investment. Brain-related injury research received $427.7 m (47.4%), orthopaedic injury $138.6 m (15.4%), eye injury $63.7 m (7.0%) and ear injury $60.5m (6.7%). Blast TBI research received a total investment of $384.3 m, representing 42.6% of all blast injury-related research. The U.S. Department of Defense funded $719.3 m (80%).ConclusionsInvestment data suggest that blast TBI research has received greater funding than other blast injury health areas. The funding pattern observed can be seen as reactive, driven by the response to the War on Terror, the rising profile of blast TBI and congressionally mandated research.

Q-tip ear injury with stapes luxation into the vestibule-a case report

<p>Stapediovestibular luxation by Q-tip ear injury is a rare occurrence. The traumatic context associated with cochleovestibular symptoms should lead to a high index of suspiscion. Temporal bone CT scan confirms the diagnosis. The authors report a case of stapediovestibular luxation and discuss the management of this condition. An 8-year-old boy presented to our department for otalgia, hearing loss, and dizziness. The history revealed a penetrating right ear injury by Q-tip, which had occurred 5 days previously. ENT examination found a right peripheral vestibular syndrome with ipsilateral tympanic perforation. Tonal audiometry noted right cophosis. Temporal bone CT scan showed right side internal stapediovestibular dislocation. Middle ear inspection with oval window fistula repair and tympanic closure were performed. Postoperative outcomes showed complete resolution of vestibular symptoms without improvement of sensorineural hearing loss thresholds. Traumatic stapediovestibular dislocation by Q-tip ear injury is unusual. Early diagnosis, with precise lesion assessment and appropriate management resolve vestibular symptoms, prevent infectious complications. But, hearing outcomes are variable.</p><p> </p>

Yield, Insect-Derived Ear Injury, and Aflatoxin Among Developmental and Commercial Maize Hybrids Adapted to the North American Subtropics

The development of maize (Zea mays L.) hybrids that are adapted to subtropical areas of North America should consider yield potential under heat and moisture stress, and reduced susceptibility to insect herbivory and disease. To aid in this process, maize hybrids (43 developmental and seven non-Bt commercial hybrids) were evaluated for severity of ear injury to Helicoverpa zea (Boddie) and Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), susceptibility to Aspergillus flavus (Link) (Deuteromycetes: Moniliales), and yield. In subtropical Corpus Christi and College Station, TX, field experiments conducted over three years revealed significant differences among maize hybrids with the rank of the selected measurements differing across the two locations. When the location by maize hybrid interaction was not significant, variation across the main factors of maize hybrid genetics (in all cases) and location (in some cases) was detected. In 2014, a significant location by maize hybrid interaction in yield but not aflatoxin and ear injury were likely associated with differences in weather between locations. In Corpus Christi in 2015, a location by maize hybrid interaction was detected for ear injury only. Overall, experimental maize hybrids, containing the inbred line Tx777, displayed partial resistance to insect derived ear injury in both locations, and some hybrid testcrosses exhibited low rates of aflatoxin accumulation while maintaining relatively high yields. Tx777 was selected from populations originating in Bolivia and adapted to subtropical climates. The most promising hybrid testcrosses had lower ear injury and aflatoxin accumulation, and good yield under varying heat and moisture stress at the two subtropical maize growing areas in this study.