Sunday, December 13, 2020

Characterization of Sensorineural Hearing Loss in Adult Patients With Sickle Cell Disease: A Systematic Review and Meta-analysis

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imageObjectives and Main Outcome Measures: To determine the prevalence of sensorineural hearing loss (SNHL) attributable to sickle cell disease (SCD) in the global adult population and to identify factors contributing to its severity. Study Design: Systematic Review and Meta-analysis. Methods: We performed a comprehensive literature search for scientific articles in PubMed, Scopus, CINAHL, Web of Science, and the Cochrane Library that reported the incidence of hearing loss in populations over 18 years of age with SCD. Results: We identified 138 studies from the initial search, 12 of which met inclusion criteria and were utilized for data analysis. A total of 636 SCD patients and 360 controls were included in the Cochrane Review Manager 5.3 meta-analysis. There was a statistically significant increase in the prevalence of SNHL in adults with SCD compared with the general population with a cumulative risk ratio (RR) of 6.03. Conclusions: This is the first systematic investigation of the relationship between SCD and SNHL in adult patients across the globe. SNHL is more prevalent in patients with SCD, specifically those of the HbSS genotype, than the general population likely due to the pathophysiology of the disease and its effects on labyrinthine microvasculature. The increased prevalence of SNHL in the adult SCD population warrants future research into the predictors of SNHL severity and merits routine audiometric monitoring of adult SCD patients.
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Otosclerosis in an Urban Population

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imageObjective: To investigate the evolving prevalence of otosclerosis in a large urban population. Methods: A retrospective review of patients in a large, urban, public health system was conducted from January 2010 to August 2019 to identify subjects with otosclerosis. Diagnostic testing included audiometry and computed tomography scans. Sex, age at diagnosis, treatment received, race, ethnicity, and country of birth were analyzed for each subject and compared with all eligible patients in the reference population. Results: A total of 134 patients from a reference population of 672,839 were diagnosed with otosclerosis and analyzed. The otosclerosis patients were predominantly Hispanic (73%), of which the majority were foreign born (87%). The average age at onset was 46 years and 59% were women. The overall prevalence of otosclerosis was 20 of 100,000 patients. The crude prevalence of otosclerosis by ethnicity was 43 of 100,000 for Hispanics, 12.6 of 100,000 for Caucasians, and 3 of 100,000 for African Americans. Within the Hispanic population, the prevalence of otosclerosis was 60 of 100,000 for foreign-born individuals and 16 of 100,000 for those born in the USA (odds ratio [OR] = 3.69, [95% confidence interval [CI], 2.02–6.76], p 
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Quinine in Otology and Neurotology: Ototoxicity and Historic Role in Therapy

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imageObjectives/Hypothesis: Quinine, a cinchona bark-derived antimalarial alkaloid, is a known ototoxic. Isolated and named in 1820 by the French scientists Pierre-Joseph Pelletier and Joseph-Bienaimé Caventou, it has since been employed in the treatment of different maladies. Quinine was also recommended as a local anesthetic in surgical procedures in the early 20th century. This article aims to identify early ototoxicity reports regarding quinine and to investigate if quinine was previously used in otology as an anesthetic agent or as an actual therapy. Method: Historical review of medical and pharmaceutical literature from the 19th and 20th centuries in databases (PubMed; Web of Science), as well as medical books on ototoxic drugs, quinine, and therapies in otology. Results: The first identified reference of quinine ototoxicity was from 1824. Quinine also had a therapeutic role in otology and neurotology and was employed for its analgesic properties. It was used in Menière's disease, vertigo, otalgia, purulent otitis media, neuralgia of the plexus tympani, furuncles in the auditory canal, and herpes zoster in the auricle. Conclusion: Quinine was acknowledged as an ototoxic drug in the 19th century. Quinine was used in several otologic disorders, both as an analgesic (for herpes zoster, otalgia) and as a therapeutic agent (Menière's disease, vertigo, purulent otitis media, furuncles in the auditory canal). This research demonstrates that, analogously to gentamicin, quinine was used in Menière's disease specifically due to its ototoxic effects.
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Cochlear Dysfunction Is a Frequent Feature of Facioscapulohumeral Muscular Dystrophy Type 1 (FSHD1)

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imageIntroduction: Facioscapulohumeral muscular dystrophy type 1 (FSHD) represents one of the most common forms of muscular hereditary diseases and it is characterized by a great clinical variability with the typical muscular symptoms and other clinical features, including hearing impairment. However, etiopathogenetic mechanisms of auditory dysfunction are still not completely understood and it has been suggested that it could be assigned to a cochlear alteration that is present even in those subjects with a normal pure tonal audiometry (PTA) examination. Methods: We found out the cochlear function in 26 patients with molecular diagnosis of FSHD1 and in healthy controls. All patients underwent complete neurological and audiological examinations, including FSHD clinical score, pure-tone audiometry (PTA), and otoacoustic emissions (OAEs), in particular transient evoked otoacoustic emissions (TEOAEs) and distortion product evoked otoacoustic emissions (DPOAEs). Results: All FSHD1 patients showed significantly reduced DPOAEs and TEOAEs, bilaterally and at all frequencies, even when considering only subjects with a normal PTA or a mild muscular involvement (FSHD score ≤ 2). No correlation between OAEs and FSHD clinical score was found. Discussion: Cochlear echoes represent a sensitive tool in detecting subclinical cochlear dysfunction in FSHD1 even in subjects with normal hearing and/or subtle muscle involvement. Our study is focused on the importance of evaluating the cochlear alteration through OAEs and, in particular, by performing TEOAEs and DPOAEs sequentially, to evaluate more frequent specificities of cochlear dysfunction with a wider spectrum of analysis.
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A Comparison of Dizziness Handicap Inventory Scores by Categories of Vestibular Diagnoses

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imageObjective: The Dizziness Handicap Inventory (DHI) is a 25-item self-report quantifying dizziness-related physical and emotional symptoms and restrictions in daily activities. DHI scores do not correlate with severity of structural vestibular deficits; thus, high DHI scores may reflect other causes of morbidity. This study investigated the relationship between total DHI scores and the presence of structural, functional, and psychiatric disorders in tertiary neurotology patients. Study Design: Retrospective. Setting: Tertiary center. Patients: Eighty-five patients who underwent multidisciplinary neurotologic evaluations. Intervention: Diagnostic. Main Outcome Measure(s): Active illnesses identified by a multidisciplinary neurotology team were abstracted from medical records, cataloged as structural, functional, or psychiatric disorders, and used to group patients into diagnostic categories: structural (structural disorders only), functional (functional disorders with/without structural disorders), and psychiatric (psychiatric disorders with/without other conditions). DHI scores were compared across diagnostic categories. Sensitivities and specificities of DHI scores for identifying structural versus functional or psychiatric disorders were calculated. Results: Mean DHI scores differed significantly by diagnostic category (structural 35 ± 18, functional 64 ± 15, and psychiatric 65 ± 19), before and after adjusting for age and sex (p 1.62 for structural versus functional and psychiatric categories). DHI≤30 (mild handicap) had specificity = 0.98 for structural disorders alone, whereas DHI>60 (severe handicap) had specificity = 0.88 for functional or psychiatric disorders. Conclusions: In this tertiary cohort, categories of illnesses had large effects on total DHI scores. Patients with scores ≤30 were likely to have structural disorders alone, whereas those with scores >60 were likely to have functional or psychiatric disorders, with or without coexisting structural conditions.
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Within-Subject Comparisons of the Auditory Brainstem Response and Uncomfortable Loudness Levels in Ears With and Without Tinnitus in Unilateral Tinnitus Subjects With Normal Audiograms

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imageObjective: To evaluate whether cochlear synaptopathy is a common pathophysiologic cause of tinnitus in individuals with normal audiograms. Study Design: Prospective study. Setting: Tertiary referral center. Methods: We enrolled 27 subjects with unilateral tinnitus and normal symmetric hearing thresholds, and 27 age- and sex-matched control subjects with normal symmetric hearing thresholds. We measured 1) the amplitudes of waves I and V with 90 dB nHL click stimuli in quiet conditions; 2) the latency shift of wave V with 80 dB nHL click stimuli in background noise, varying from 40 dB HL to 70 dB HL; and 3) uncomfortable loudness levels (UCLs) at 500 Hz and 3000 Hz pure tones. Results: There were no significant differences in the wave V/I amplitude ratio or the latency shift in wave V with increasing noise levels among the tinnitus ears (TEs), nontinnitus ears (NTEs), and control ears. There were no significant differences in UCLs at 500 Hz or 3000 Hz between TEs and NTEs, but the UCLs were lower in TEs (mean 111.3 dB or 104.1 dB) and NTEs (mean 109.4 dB or 100.6 dB) than in control ears (mean 117.9 dB or 114.1 dB, p 
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Pharmacological Prevention of Noise-induced Hearing Loss: A Systematic Review

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imageObjective: This study aims to explore and determine the effectiveness of current pharmacologic agents for the prevention of noise-induced hearing loss (NIHL) via a systematic review. Databases Reviewed: The PubMed, Scopus, ClinicalTrials.gov, and Cochrane Library databases were searched from inception through February 6, 2020. Methods: Full-text, English-language articles detailing prospective randomized and nonrandomized clinical trials with pharmacological interventions administered to prevent NIHL were included in accordance with PRISMA guidelines. The detailed search terms are included in the Appendix, http://links.lww.com/MAO/B67. Results: Eleven articles were included in this review with 701 patients receiving a pharmacologic prevention for various noise exposures. Various regimens included administration of alpha-lipoic acid, ambient oxygen, beta-carotene, carbogen, ebselen, Mg-aspartate, N-acetylcysteine, and vitamins C, E, and B12. A number of studies demonstrated statistically significant amelioration of NIHL with pharmacologic intervention. Two studies demonstrated significantly better hearing outcomes for pharmacological prophylaxis with carbogen or ebselen as compared with placebo for the 4 kHz frequency, where the noise-notch is most likely to be encountered. Given the considerable heterogeneity in agents and methodologies, however, it was not possible to conduct a meta-analysis. Conclusions: While several heterogenous articles demonstrated promising results for Mg-aspartate, carbogen, vitamin B12, and alpha-lipoic acid, the clinical significance of these pharmaceuticals remains unclear. Initial data from this study alongside future clinical trials might potentially contribute to the generation of clinical practice guidelines to prevent NIHL. Level of Evidence: 2
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Endoscopic Intervention of Aberrant Carotid Artery in the Middle Ear

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imageObjective: To describe surgical management for transcanal endoscopic ear surgery (TEES) in two patients with aberrant internal carotid artery (ICA) in the middle ear. Patients: A young girl who complained of pulsatile tinnitus and an elderly man who presented with ear bleeding. Otoendoscopy examination revealed a pulsatile reddish mass protruding through the tympanic membrane in both patients. Interventions: A combination of clinical assessments and imaging supported the diagnosis of aberrant ICA in the middle ear. Transcanal endoscopic reinforcement of the artery was performed; tragal cartilage was used as a shield to strengthen the carotid canal defect. Results: Assisted by fine endoscopic instruments, the protruding arteries were separated without damage to the surrounding structures and reinforced using tragal cartilage. Both patients' symptoms improved postoperatively; they reported tinnitus relief and hearing improvement. Conclusion: To prevent catastrophic events, diagnosis of aberrant ICA is important before any surgical intervention. With appropriate management, surgical intervention using transcanal endoscopic ear surgery offers a clear view of the surgical field and is an excellent choice for management of aberrant ICA.
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Mutations in DNA Repair Genes and Clinical Outcomes of Patients With Metastatic Colorectal Cancer Receiving Oxaliplatin or Irinotecan-containing Regimens

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Objectives: First-line regimens in the treatment of metastatic colorectal cancer (mCRC) combine a fluoropyrimidine with oxaliplatin (FOLFOX/XELOX) or irinotecan (FOLFIRI). There is limited efficacy data to guide the selection of one treatment over the other. This study investigated whether mutations affecting DNA damage response (DDR) could differentially influence the response to oxaliplatin and irinotecan-containing regimens. Methods: We retrospectively analyzed 49 patients with mCRC for whom treatment outcomes and results of comprehensive genomic profiling of tumors were available. Specimens with at least 1 pathogenic mutation involving BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L were classified as DDR-mutated, while those without mutations were DDR-wild-type (WT). We compared the overall survival (OS), disease control rate, and response rate (RR) between the DDR-mutated and DDR-WT groups. Results: DDR mutations occurred in 11 patients (22%). First-line treatment with an oxaliplatin-containing regimen was administered to 33 patients (31 FOLFOX, 2 XELOX), while 16 patients received FOLFIRI. Among DDR-mutated cases, first-line treatment with FOLFOX/XELOX correlated with a statistically significant improvement in median OS compared with FOLFIRI (3.4 vs.1.8 y; P=0.042) and numerically higher RR (50% vs. 33%; P=0.58). No significant difference in OS (2.4 vs. 2.5 y; P=0.42), RR, disease control rate was observed between the 2 regimens in patients with DDR-WT tumors. Conclusions: Mutations in DDR genes were present in 22% of patients with mCRC. In patients with DDR-mutated tumors, initial treatment with FOLFOX/XELOX correlated with improved OS and a numerically higher RR compared with FOLFIRI. The authors declare no conflicts of interest. Reprints: Benedito A. Carneiro, MD, MS, Division of Hematology/Oncology, Lifespan Cancer Institute, The Warren Alpert Medical School of Brown University, 593 Eddy Street, George Building 302, Providence, RI 02903. E-mail: benedito_carneiro@brown.edu. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
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Tyrosinase deficiency increases protein carbonyl content in substantia nigra of mice administered retinol palmitate

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Tyrosinase is a key enzyme for the biosynthesis of melanin pigments in peripheral tissues such as skin and retina. Although tyrosinase activity is specifically detected in melanocytes, several studies have shown the expression and enzymatic activity of tyrosinase in the central nervous system, especially in the midbrain substantia nigra. In the present study, we investigated the antioxidative effects of tyrosinase on protein damage in the substantia nigra of mice. C57BL/10JMsHir (B10) and tyrosinase-deficient albino B10.C-Tyrc/Hir (B10-c) mice were intraperitoneally administered retinol palmitate to in duce oxidative stress, and the protein carbonyl content, a hallmark of protein oxidative damage, was examined in the substantia nigra. Retinol palmitate administration was found to decrease catalase activity in the substantia nigra of both B10 and B10-c mice, suggesting the induction of oxidative stress due to imbalanced antioxidant systems. In this model, we found that tyrosinase deficiency markedly increases the protein carbonyl content in the substantia nigra. Thus, we concluded that tyrosinase activity prevents protein damage in the substantia nigra of mice that were challenged with oxidative stress. These findings provide novel insight into the physiological role of tyrosinase in the central nervous system. Received 2 November 2020 Accepted 11 November 2020 Correspondence to Shu Aizawa, PhD, Laboratory of Animal Genetics and Physiology, Department of Animal Science, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-0880, Japan, Tel/fax: +81(466)84 3654; e-mail: aizawa.shu@nihon-u.ac.jp © 2020 Wolters Kluwer Health | Lippincott Williams & Wilkins
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Induced brain magnetic activities related to salient birdsong under noisy conditions

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Objective Birdsong sounds are often used to inform visually-challenged people about the presence of basic infrastructures, and therefore need to be salient in noisy urban environments. How salient sounds are processed in the brain could inform us about the optimal birdsong in such environments. However, brain activity related to birdsong salience is not yet known. Methods Oscillatory magnetoencephalographic (MEG) activities and subjective salience induced by six birdsongs under three background noise conditions were measured. Thirteen participants completed the MEG measurements and 11 participants took part in the paired-comparison tests. We estimated the power of induced oscillatory activities, and explored the relationship between subjective salience of birdsongs and the power of induced activities using sparse regression analysis. Results According to sparse regression analysis, the subjective salience was explained by the power of induced alpha (8–13 Hz) in the frontal region, induced beta (13–30 Hz) in the occipital region, and induced gamma (30–50 Hz) in the parietal region. The power of the frontal alpha and parietal gamma activities significantly varied across both birds and noise conditions. Conclusion These results indicate that frontal alpha activity is related to the salience of birdsong and that parietal gamma activity is related to differences in salience across noisy environments. These results suggest that salient birdsong under a noisy environment activates the bottom-up attention network. Received 5 October 2020 Accepted 15 November 2020 Correspondence to Yoshiharu Soeta, PhD, Medical and Biological Engineering Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Midorigaoka, Ikeda, Osaka 563-8577, Japan, Tel: +81 72 751 9496; e-mail: y.soeta@aist.go.jp © 2020 Wolters Kluwer Health | Lippincott Williams & Wilkins
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