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Vasogenic brain edema, a potentially life-threatening consequence following an acute ischemic stroke, is a major clinical problem. This research aims to explore the therapeutic benefits of nimodipine, a calcium channel blocker, in mitigating vasogenic cerebral edema and preserving blood-brain barrier (BBB) function in an ischemic stroke rat model. In this research, animals underwent the induction of ischemic stroke via a 60-min blockage of the middle cerebral artery and treated with a nonhypotensive dose of nimodipine (1 mg/kg/day) for a duration of five days. The wet/dry method was employed to identify cerebral edema, and the Evans blue dye extravasation technique was used to assess the permeability of the BBB. Furthermore, immunofluorescence staining was utilized to assess the protein expression levels of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). The study also examined mitochondrial function by evaluating mitochondrial swelling, succinate dehydrogenase (SDH) activity, the collapse of mitochondrial membrane potential (MMP), and the generation of reactive oxygen species (ROS). Post-stroke administration of nimodipine led to a significant decrease in cerebral edema and maintained the integrity of the BBB. The protective effects observed were associated with a reduction in cell apoptosis as well as decreased expression of MMP-9 and ICAM-1. Furthermore, nimodipine was observed to reduce mitochondrial swelling and ROS levels while simultaneously restoring MMP and SDH activity. These results suggest that nimodipine may reduce cerebral edema and BBB breakdown caused by ischemia/reperfusion. This effect is potentially mediated through the reduction of MMP-9 and ICAM-1 levels and the enhancement of mitochondrial function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Tracheoesophageal prosthesis (TEP) is a common method for post-laryngectomy speech rehabilitation. Despite its common use, some patients ultimately fail TEP rehabilitation. TEP dysfunction negatively affects quality of life due to poor voice quality and need for repeated interventions to restore TEP function. Occasionally, voice rehabilitation with TEP is completely unsuccessful. We performed a scoping review to characterize the main reasons for total TEP failure, in hopes of guiding selection of optimal TEP candidates., Study Design: Scoping review using PubMed of all English language articles from 1990 to 2020 addressing causes of TEP failure., Methods: This scoping review followed the population, intervention, comparison, outcome and study (PICOS) guidelines. Total TEP failure was defined as complete loss or abandonment of TEP voice or tract. A comprehensive search strategy using PubMed's MeSH subject headings and keywords was created. Causes and rates of failure were reviewed., Results: Among 544 peer-reviewed journal articles reviewed for inclusion. Seventy articles met inclusion criteria, resulting in a total of 4928 TEP voice restoration patients for analysis. 15.2% of these patients had total TEP failure. The most common reasons for failure were dissatisfaction with voice (26.3%), leakage (17.9%), inadequate patient motivation (14.7%), comorbidities (14.2%), stoma problems (11.6%), and abandonment of TEP after dislodgement (10.6%)., Conclusion: Common reasons for TEP failure included voice dissatisfaction, leakage, lack of patient motivation, patient comorbidities, and stoma problems. These factors should be considered when selecting candidates for TEP voice restoration., (© 2024 Wiley Periodicals LLC.)

Objective: To validate the efficacy of a virtual, interdisciplinary workshop in improving HPV knowledge, and vaccination practices among primary care and dental trainees., Methods: A virtual platform was utilized to hold HPV educational workshops with primary care and dental trainees. Online surveys were distributed before and after the 1-h interactive workshop, led by otolaryngology residents. Surveys included the workshop's impact on (a) improving knowledge of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and (b) affecting change in HPV vaccination practices. The vaccination rates of trainees were recorded prior to and after workshop attendance., Results: After the workshop, participants demonstrated significantly improved scores related to knowledge of HPV in the head and neck (p = 0.003) and showed an increased comfort level with counseling on HPV vaccination (p = 0.002). Respondents were also more aware that the HPV vaccine is approved to prevent OPSCC (61% vs. 95%, p < 0.05). Ninety-seven percent of respondents stated that the workshop changed their HPV vaccination practices, and 95% of those not fully vaccinated stated they would now be more likely to receive the vaccine themselves. There was a significant increase in the average number of HPV vaccines administered at the studied trainee clinic, from 16.83 vaccines/month to 37.6 vaccines/month (percent increase = 123%) in 5 months following the workshop (p = 0.002)., Conclusion: The present interactive virtual workshop demonstrates efficacy in improving HPV-related knowledge and vaccination practices among trainees. The virtual nature of the course facilitates knowledge transfer and can be used to foster multi-institutional partnerships regarding medical education and vaccination efforts., Level of Evidence: 4 Laryngoscope, 134:3096-3101, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Racial and ethnic disparities exist in the prevalence and management of osteoporosis, metastatic cancer, and sickle cell disease. Despite being the most common metabolic bone disease, osteoporosis remains underscreened and undertreated among Black women. Skeletal-related events in metastatic cancer include bone pain, pathologic fractures, and spinal cord compression. Disparities in screening for and treating skeletal-related events disproportionately affect Black patients. Metabolic bone disease contributes significantly to morbidity in sickle cell disease; however, clinical guidelines for screening and treatment do not currently exist. Clinical care recommendations are provided to raise awareness, close health care gaps, and guide future research efforts., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Tracheal perforation is an extremely rare and potentially dangerous complication of a partial thyroidectomy. The current case represents a unique presentation of delayed tracheal perforation following an uncomplicated thyroid isthmusectomy for tissue diagnosis of an aggressive appearing thyroid mass in the setting of high-dose steroid administration and recent intubation and self-extubation. While conservative management of tracheal perforation can sometimes be appropriate, our patient was successfully managed via primary closure and infrahyoid muscle transposition flap to cover a 5 mm right lateral tracheal wall defect. We recommend caution be exercised following thyroid surgery in the setting of intubation and high-dose steroids.

Comprehensive education regarding human papillomavirus (HPV) pathogenesis, vaccination, and patient counseling are not routinely included in the medical school curriculum; consequently, student and provider knowledge, especially concerning head and neck pathology, remains low. The objective of this study was to demonstrate long-term retention of HPV knowledge and positive attitudes towards HPV vaccination after attending our novel HPV workshop, with a focus on knowledge of oropharyngeal cancer. A follow-up survey was administered to medical students 1.5 years after the initial completion of the workshop. HPV vaccination records from the student-led clinic were collected from the immunization information system. Awareness that HPV causes oropharyngeal cancer was present in 33% of medical students pre-curriculum; immediate and long-term post-curricular awareness of this association remained at 90% or higher (p < 0.0001). Comfort with HPV counseling, having enough information to recommend the vaccine, and knowledge of HPV malignancies, symptoms, transmission, and vaccination schedule remained persistently elevated over pre-curriculum scores (p < 0.05). Long-term knowledge scores were also higher than a control group of medical students at the same stage of training who had never participated in the workshop (p < 0.05). HPV vaccination rates at the medical school's student-run clinic also increased after the curriculum, from an average of 1.89 HPV vaccines given per clinic to 3.55 (p = 0.001). This study demonstrates that knowledge and positive attitudes were maintained 1.5 years after participating in this HPV curriculum during students' preclinical years of medical school. Additionally, an increase in HPV vaccination rates occurred at a student-led clinic, indicating a positive clinical impact on the curriculum., (© 2021. American Association for Cancer Education.)

Objectives/hypothesis: Phonation threshold pressure (P th ) is the minimum subglottic pressure required to reach phonation onset and is considered a marker for vocal efficiency and health. We investigated the effects of intrinsic laryngeal muscle (ILM) activation on P th ., Study Design: In vivo animal study., Methods: In an in vivo canine phonation model, laryngeal adductor muscles were activated together by stimulation of the recurrent laryngeal nerves (RLNs) and individually via stimulation of respective terminal nerve branches. Cricothyroid (CT) muscles were activated via stimulation of the superior laryngeal nerves. ILMs were activated in a graded manner at various combinations as transglottal airflow was gradually increased. Aerodynamic and glottal posture parameters were measured at phonation onset., Results: Graded RLN stimulation decreased glottal distance and increased P th . Thyroarytenoid (TA) muscle activation alone increased P th . Lateral cricoarytenoid (LCA) muscle activation alone had minimal effects. However, graded TA activation as a function of LCA activation level revealed a synergistic relationship between the two muscles in increasing P th . Effects of CT activation were dependent on adductor stimulation level: CT activation increased P th at low RLN stimulation levels and decreased P th at high RLN levels., Conclusions: The effects of ILM activation on P th were consistent with their expected effects on vocal fold stiffness and tension. TA was the primary adductor controlling P th . While LCA alone had minimal effects on P th , it enhanced the role of TA in controlling P th . TA and CT have antagonistic roles in controlling P th . These relationships should be considered in clinical efforts to improve ease of phonation and vocal efficiency., Level of Evidence: NA, basic science Laryngoscope, 132:1427-1432, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: We aim to clarify the national scope of unmet pediatric hearing care needs and identify specific barriers to hearing care., Study Design: Cross-sectional study of a nationally representative data set., Setting: This study is based on the combined 2016 and 2017 National Survey of Children's Health. This survey covers the physical and emotional health, access to care, and social context of US children and adolescents aged 0 to 17 years., Methods: Analysis of parent-reported responses of children's hearing status, access to care, and perceived barriers., Results: Overall, 0.3% (n = 206,200) of US children surveyed reported needing hearing care, which was not received. A further 1.3% (n = 934,000) reported deafness or problems with hearing, and of these, 6.4% (n = 60,000) reported not receiving necessary hearing care. Rates of insurance coverage between children with deafness/hearing problems and the general population were similar (91.7% vs 93.9%); however, deaf or hard-of-hearing children with unmet hearing care needs were more likely to be from non-White backgrounds (P = .009) and to lack health insurance coverage (P = .001). Rates of unfulfilled hearing care by reason were as follows: 57.5% without eligibility for the service, 45.4% reporting the service was not available in their area, 53.7% with difficulty obtaining an appointment, and 53.5% reporting issues with cost., Conclusion: Over 200,000 children annually do not receive necessary hearing-related care despite high rates of insurance coverage, and nearly 60,000 of these children are deaf or hard of hearing. Cost, eligibility for and distribution of services, and timely appointments are the primary barriers to hearing health care.

Objectives: Laryngeal vibratory asymmetry occurring with paresis may result in a perceptually normal or abnormal voice. The present study aims to determine the relationships between the degree of vibratory asymmetry, acoustic measures, and perception of sound stimuli., Study Design: Animal Model of Voice Production, Perceptual Analysis of Voice., Methods: In an in vivo canine model of phonation, symmetric and asymmetric laryngeal vibration were obtained via graded unilateral recurrent laryngeal nerve (RLN) stimulation simulating near paralysis to full activation. Phonation was performed at various contralateral RLN and bilateral superior laryngeal nerve stimulation levels. Naïve listeners rated the perceptual quality of 182 unique phonatory samples using a visual sort-and-rate task. Cepstral peak prominence (CPP) was calculated for each phonatory condition. The relationships among vibratory symmetry, CPP, and perceptual ratings were evaluated., Results: A significant relationship emerged between RLN stimulation and perceptual rating, such that sound samples from low RLN levels were preferred to those from high RLN levels. When symmetric vibration was achieved at mid-RLN stimulation, listeners preferred samples from symmetric vibration over those from asymmetric vibration. However, when symmetry was achieved at high RLN levels, a strained voice quality resulted that listeners dispreferred over asymmetric conditions at lower RLN levels. CPP did not have a linear relationship with perceptual ratings., Conclusions: Laryngeal vibratory asymmetry produces variable perceptual differences in phonatory sound quality. Though CPP has been correlated with dysphonia in previous research, its complex relationship with quality limits its usefulness as clinical marker of voice quality perception., Level of Evidence: NA, basic science Laryngoscope, 131:2740-2746, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Lipomas are common benign mesenchymal neoplasms. Although 13% of lipomas are found in the head and neck, only 0.6% have been reported in the larynx. Of all lipomas, the spindle cell variant is the least common. In the present study, we report a case of supraglottic spindle cell lipoma and review the literature of laryngeal spindle cell lipoma. A 35-year-old male presented with dysphagia and dyspnea and was found to have bilateral supraglottic lesions causing airway obstruction. The masses were resected endoscopically. Final pathology demonstrated mature adipocytes and spindle cells, with immunohistochemical patterns supportive of spindle cell lipoma. Spindle cell lipomas have rarely been reported in the upper airway. To our knowledge, this is the youngest patient reported to date. These lipomas are uncommon benign neoplasms and should be distinguished from aggressive mesenchymal neoplasms such as liposarcoma variants to guide appropriate conservative but curative therapy., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To understand national trends in 30-day postoperative readmission following inpatient pediatric tonsillectomy and adenoidectomy., Study Design: Retrospective cohort study., Setting: Nationwide Readmissions Database., Methods: We used the Nationwide Readmissions Database to identify and analyze 30-day readmissions following inpatient tonsillectomy from 2010 to 2015. Using the International Classification of Disease codes, we identified 66,652 patients and analyzed the incidence, causes, risk factors, and costs of 30-day readmission., Results: Of 66,652 patients who underwent inpatient tonsillectomy, 2660 (4.0%) experienced a readmission. Readmitted patients were more commonly aged <2 years (23.4 vs 10.6%, P = .01) and had a greater burden of comorbidities, including preoperative anemia (3.9 vs 1.3%, P < .001), coagulopathy (3.5 vs 1.4%, P < .001), and neurologic disorders (19.1 vs 6.6%, P < .001). Readmitted patients experienced higher rates of postoperative complications (17.4 vs 9.0%, P < .001) and had a longer length of stay (4.5 vs 2.2 days, P < .001). Index cost of hospitalization was higher among readmitted patients ($14,129 vs $7307, P < .001), and each readmission cost an additional $7576. Postoperative hemorrhage (21.3%) and dehydration (17.7%) were the 2 most common causes for readmission. Independent predictors of readmission included age <3 years, multiple comorbidities, and postoperative neurologic complications. The incidences of tonsillectomies and readmissions declined during the study period, most notably between 2010 and 2012., Conclusion: Readmission after inpatient tonsillectomy and adenoidectomy places a substantial financial burden on the health care system. Targeted strategies to improve preoperative assessment and optimize postoperative care may prevent readmission, reduce unnecessary health care expenditures, and improve patient outcomes.

Manipulation of the phosphatase and tensin homolog (PTEN) pathway has been suggested as a therapeutic approach to treat or prevent vision loss due to retinal disease. In this study, we investigated the effects of deleting one copy of Pten in a well-characterized class of retinal ganglion cells called α-ganglion cells in the mouse retina. In Pten +/- retinas, α-ganglion cells did not exhibit major changes in their dendritic structure, although most cells developed a few, unusual loop-forming dendrites. By contrast, α-ganglion cells exhibited a significant decrease in heterologous and homologous gap junction mediated cell coupling with other retinal ganglion and amacrine cells. Additionally, the majority of OFF α-ganglion cells (12/18 cells) formed novel coupling to displaced amacrine cells. The number of connexin36 puncta, the predominant connexin that mediates gap junction communication at electrical synapses, was decreased by at least 50% on OFF α-ganglion cells. Reduced and incorrect gap junction connectivity of α-ganglion cells will affect their functional properties and alter visual image processing in the retina. The anomalous connectivity of retinal ganglion cells would potentially limit future therapeutic approaches involving manipulation of the Pten pathway for treating ganglion cell degeneration in diseases like glaucoma, traumatic brain injury, Parkinson's, and Alzheimer's diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Azar, Harris, Brecha and Pérez de Sevilla Müller.)

The transcription factor Prox1 is expressed in multiple cells in the retina during eye development. This study has focused on neuronal Prox1 expression in the inner nuclear layer (INL) of the adult mouse retina. Prox1 immunostaining was evaluated in vertical retinal sections and whole mount preparations using a specific antibody directed to the C-terminus of Prox1. Strong immunostaining was observed in numerous amacrine cell bodies and in all horizontal cell bodies in the proximal and distal INL, respectively. Some bipolar cells were also weakly immunostained. Prox1-immunoreactive amacrine cells expressed glycine, and they formed 35 ± 3% of all glycinergic amacrine cells. Intracellular Neurobiotin injections into AII amacrine cells showed that all gap junction-coupled AII amacrine cells express Prox1, and no other Prox1-immunostained amacrine cells were in the immediate area surrounding the injected AII amacrine cell. Prox1-immunoreactive amacrine cell bodies were distributed across the retina, with their highest density (3887 ± 160 cells/mm 2 ) in the central retina, 0.5 mm from the optic nerve head, and their lowest density (3133 ± 350 cells/mm 2 ) in the mid-peripheral retina, 2 mm from the optic nerve head. Prox1-immunoreactive amacrine cell bodies comprised ~9.8% of the total amacrine cell population, and they formed a non-random mosaic with a regularity index (RI) of 3.4, similar to AII amacrine cells in the retinas of other mammals. Together, these findings indicate that AII amacrine cells are the predominant and likely only amacrine cell type strongly expressing Prox1 in the adult mouse retina, and establish Prox1 as a marker of AII amacrine cells.

Background: Hepatitis B virus (HBV) is a key factor for hepatocellular carcinoma (HCC). About 350 million people are affected by chronic infection which is related to the rapid development of liver diseases as well as hepatitis, cirrhosis and hepatocellular carcinoma. Expression of tumor necrosis factor alpha (TNFα) in the liver demonstrates a major genetic polymorphism which is involved in resistance or susceptibility to chronic HBV infection., Materials and Methods: In this study, two populations were studied by the sequence specific primerpolymerase chain reaction (SSPPCR) method: HBV cases (n=409), who were HBSAg+, and healthy controls (n=483)., Results: The results shown that the frequency of TNFα 308 G/G genotype in healthy controls (47.2%) was significantly higher than in HBV infected patients (28%) (CI = 1.292.61, OR = 1.83, P = 0.0004). Also TNFα 308 A/A and A/G genotype frequencies in the healthy controls were 4.6% and 48.2% and in patient group were 19.5% and 52.5% (CI = 2.237.12, p: 0.0001, OR: 3.94) respectively., Conclusions: We found that among Iranian people TNFα 308A allele not only has the highest genotype frequency but also it has the highest frequency in the world population. In addition, TNFα308 G/G polymorphism was associated with HBV resistance, whereas TNFα308A (A/A or A/G) polymorphism appeared to associated with chronic HBV infection. These data suggested that among the Iranian population, the 308 G/G polymorphism of TNFα gene promoter region has the potential to influence the susceptibility to HBV infection and it may be responsible for viral antigen clearance.

Background: Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Cytokines play an important role in the regulation of immune responses and defense against viral infections. Human interleukin 6 (IL6) is a multifunctional cytokine that participates in these processes., Objective: The aim of this study was to assess the IL6-174 gene polymorphism in patients with chronic hepatitis B virus (HBV) infection as compared with healthy controls in an Iranian population., Materials and Methods: Totals of 297 HBV patients and 368 control individuals were evaluated. Genomic DNA was extracted from peripheral blood and the SSP-PCR (sequence specific primer-polymerase chain reaction) method was applied for genotyping., Results: The frequencies of genotypes C/C, G/G and C/G in HBV cases were 4.7%, 34.3%, 60.9% and in controls were 12.8%, 39.7% and 47.6%, respectively. The frequencies of G and C allele in patients and controls were 78.1%, 21.9% and 67.4%, 32.6 % respectively. There was a significant difference in the frequencies of G/G genotype (CI=1.8-7.1, OR=3.47, P=0.00001) and G allele (CI=1.34-2.23, OR=1.72, P=0.0001) between HBV patients and the control group., Conclusions: These findings suggest that the IL6-174 C/G genotype and the G allele are strongly associated with susceptibility to HBV infection. Demographic information showed that most of the subjects were male (74.4%). According to high frequency of G/G genotype in male participants (63.1%) men probably are more susceptible to hepatitis than women.

Enterotoxin-producing Escherichia coli are major causes of pediatric diarrhea in developing countries. The heat-stable enterotoxin of Escherichia coli (STa) causes diarrhea by virtue of its ability to bind to and stimulate intestinal membrane-bound guanylate cyclase, generating cyclic GMP (cGMP). Previous work showed that a fucosylated oligosaccharide fraction of human milk was able to protect suckling mice from the secretory effects of STa, but the mechanism of the protection could not be determined. Oligosaccharide fractions from human milk were tested for their ability to block the biochemical effects of STa in T84 cells, a human colon carcinoma line responsive to the toxin. Total and fucosylated oligosaccharide fractions were found to inhibit STa-stimulated guanylate cyclase activity in T84 cell membranes and cGMP production in intact T84 cells by 60-80%. In addition, the total oligosaccharide fraction and the fucosylated oligosaccharide fraction inhibited 125I-STa binding significantly (17% and 27% inhibition, respectively). These findings demonstrate the protective activity of human milk oligosaccharides against STa in a human-derived cell line and show that the biochemical step blocked by oligosaccharides is STa-mediated stimulation of guanylate cyclase. This represents a novel mechanism by which human milk oligosaccharides protect against diarrhea.