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The ultracytochemical localization of adenylate cyclase (AC) and guanylate cyclase B (GC-B) and C (GC-C) activity was studied after stimulation with pituitary adenylate cyclase activating peptide, C-type natriuretic peptide and guanylin, respectively, in normal human respiratory nasal mucosa and mucosa of nasal polyps. To demonstrate these enzymatic activities, we employed enzyme-ultracytochemical methods for electron microscopy. Both normal and pathologic nasal mucosa contained AC, GC-B and GC-C activity. In the upper portion of respiratory epithelium, the enzymes were detected on ciliary and microvillar membranes. In ciliary membranes, GC-B was the predominant form expressed. In goblet cells and in glands of the lamina propria, enzymatic activities were localized mainly on plasma membranes and on membranes lining secretory granules. The results did not reveal any evident differences between the enzymatic activities in normal and pathological nasal mucosa and suggest complementary activities for these enzymes and their stimulators in the regulation of mucociliary transport and glandular secretion.

Objective: Tinnitus Retraining Therapy (TRT) is a rehabilitation approach for tinnitus that is currently considered an effective treatment with an elevated response rate. TRT is usually delivered through sound generators; however, they are often difficult to find and expensive. Recently, mobile apps have been proposed for TRT. This study aims to verify the effectiveness of TRT performed using mobile apps in reducing the adverse effects of tinnitus on the quality of life., Patients and Methods: A total of 80 patients affected by tinnitus in category 0 (mild tinnitus) and category 1 (moderate tinnitus), according to the Jastreboff classification, were included in the study. Patients of both classes were subsequently differentiated into two homogeneous groups; the first (Group A) was treated with a traditional sound generator, and the second (Group B) using a mobile app. The Tinnitus Handicap Inventory - the Italian version of the questionnaire - was used to investigate the impact of tinnitus on the quality of life in enrolled patients and evaluate their response to TRT., Results: A significant improvement was found in THI scores in category 0 patients for both sound generator and mobile app groups; no difference was found between the two-treatment delivery technology (-1.186, p=0.783); conversely, tinnitus improvements in category 1 patients were only reported for subjects treated using a sound generator (-14.529, p<0.001), while no significant improvement was found in patients treated using the mobile app., Conclusions: This study confirms the value of TRT, which in patients with mild tinnitus (category 0), can also be delivered through mobile apps with results comparable to traditional sound generators. Further studies are necessary to confirm the effects of the different tinnitus treatments available and improve the knowledge on this topic.

Purpose: Nasal pathologies are characterized by a symptomatology that hardly allows to distinguish allergic rhinitis (AR), non-allergic rhinitis (NAR), and chronic rhinosinusitis (CRS). Nasal cytology (NC) has shown increasing importance in helping the clinician to differentiate the various phenotypes of rhinitis. NC allows us to evaluate nasal cellularity by distinguishing AR and various types of NAR. The objective of the study is to assess the diagnostic performance of the NC by evaluating its sensitivity, specificity, and predictive value., Methods: We recruited 387 patients with persistent rhinitis symptoms, and nasal cytology was performed. The rhinocytogram was obtained by reading for fields and the cellular count was made using quantitative and semi-quantitative grading together., Results: Two hundred and fifteen patients (55.5%; 38 had acute rhinitis, 24 acute sinusitis, 153 chronic rhinosinusitis) out of 387 referred nasal symptoms. Cytological specimen showed a mean of 94 ± 4% ciliated cells, 29 ± 0.2% mucinous cells, 16 ± 0.1% neutrophils, 11 ± 0.08% eosinophils, 4 ± 0.03 lymphocytes, 4 ± 0.03% mast cells, and 4 ± 0.01% other cells. NC was positive in 271 cases (70%). After revision of medical history, 153 patients (39%) were considered positive for NAR. Test sensibility was 100% (95% CI 97-100), specificity was 49.6% (95% CI 43-56%). Positive predictive value (PPV) was 56% (95% CI 50-62%), and negative predictive value (NPV) was 100% (95% CI 96-100%). The positive likelihood ratio was 1.98 (95% CI 1.75-2.25). Accuracy of the test was 69.5% (95% CI 64.6-74.0%)., Conclusion: Our data showed ability to identify the true-positive patients with NAR but a low ability to identify the true-negative patients, with a global accuracy of 69.5%., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The awareness of audio-vestibular side effects of drugs, such as hearing loss, tinnitus, dizziness and vertigo, has widely increased in the recent years. The present guide represents an update of the previous documents published by the authors in 2005 and 2011 on drug-induced ototoxicity and vestibulotoxicity., Materials and Methods: The authors performed a comprehensive analysis of audio-vestibular side effects of commercially available drugs based on the British National Formulary, a pharmaceutical reference book that contains a wide range of useful information and advice on prescription and pharmacology., Results: Commercially available drugs and their active principles have been classified based on their audio-vestibular side effects, as reported by the pharmaceutical companies and/or health agencies. Drugs have been categorized based on the field of application, the therapeutic indication and the pharmacological properties., Conclusions: General practitioners, otolaryngology, neurology and audiology specialists should be aware of possible audio-vestibular side effects of drugs, such as hearing loss, tinnitus, dizziness and vertigo. The present guide represents a practical tool to rapidly identify potential audio-vestibular side effects of drugs as reported by the pharmaceutical companies and/or health agencies.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, accounting for approximately 6% of all cancer cases and responsible for an estimated 1-2% of all cancer deaths. Much research evidence has accumulated in the recent years on the changes in the expression of pro-inflammatory and, to a lesser extent, anti-inflammatory cytokines, that (i) may have a role in the malignant transformation of HNSCC, (ii) may be used as diagnostic markers in the sera of patients because of their excessive production by the tumor cells and (iii) may act as possible immunotherapeutic targets. Among pro-inflammatory cytokines, interleukin-8 (IL--8) has been reported to have an important role in cancer invasion, angiogenesis and metastasis. Recent studies have shown an increased concentration of IL--8 in patients with HNSCC and a positive association with lymph node metastasis and tumor classification, although IL--8 was not significantly associated with shorter overall survival and cancer progression-free survival. Additional evidence on the pathological mechanism of origin, invasion, and metastasis of HNSCC, as well as a better understanding of the implications of cytokines, chemokines and growth factors, are of paramount importance for the advancement of research in head and neck oncology.

The association between hyperacusis and developmental disorders such as autism spectrum disorders has been extensively reported in the literature; however, the specific prevalence of hyperacusis in attention deficit hyperactivity disorder (ADHD) has never been investigated. In this preliminary study, we evaluated the presence of hyperacusis in a small sample of children affected by ADHD compared to a control group of healthy children. Thirty normal hearing children with a diagnosis of ADHD and 30 children matched for sex and age were enrolled in the study. All children underwent audiological and multidisciplinary neuropsychiatric evaluation. Hearing was assessed using pure tone audiometry and immittance test; ADHD was diagnosed following the Diagnostic and Statistical Manual of Mental Disorder criteria. Hyperacusis was assessed through the administration of a questionnaire to parents and an interview with children. Hyperacusis was diagnosed in 11 children (36.7%) in the study group and in four children (13.3%) in the control group; this difference was statistically significant ( p = 0.03). The preliminary results of this study suggest a higher presence of hyperacusis in children with attention deficit hyperactivity disorder compared to control children. More studies on larger samples are necessary to confirm these results., Competing Interests: The authors declare no conflict of interest.

Noise is a well-known risk factor in occupational medicine. Several studies have been performed in workplaces with noise sources, especially in the industrial field; on the contrary, only a few studies have been carried to evaluate the noise exposure effects in non-industrial workplaces such as small factories, handicraft laboratories, and dental laboratories. The aims of this study were to evaluate workplace noise exposure and hearing thresholds in dental technicians. Four laboratories and 51 dental technicians were included in the study. Noise exposure levels during a nominal eight-hour working day (LEX, 8 h) were assessed in the included laboratories. Audiometric thresholds with pure tone audiometry were performed in 51 dental technicians, and results were compared with those expected in subjects not exposed to noise. The environmental noise measures showed moderate differences of the LEX, 8 h among the four laboratories (range 71.4 to 76.2); average LEX, 8 h was 73.9 ± 2.2 dB(A). The audiometric results showed a progressive increase of hearing threshold values at the frequencies mostly involved in noise-induced hearing loss (3, 4 and 6 kHz) and a correlation with age and working seniority especially in males (p<0.005). Nevertheless, in the 92.1% of subjects the threshold increases were in line with those expected in subjects of the same age and sex not exposed to noise and in the remaining 7.8% were not statistically significant (p>0.05). In 3.9% of the cases the increases were bilateral, typical of noise-induced hearing loss, and only 1.9% showed involvement of several frequencies with worsening of expected thresholds >25 dB. In conclusion, our study showed that exposure to noise in dental laboratories was not sufficient to represent a hazard to hearing, as demonstrated by the LEX, 8 h, which were below 80 dB(A) and therefore below the European exposure limit values and exposure action values for workers.

Giant Cell Arteritis (GCA), or Horton's Arteritis, is a chronic form of vasculitis of the large and medium vessels, especially involving the extracranial branches of the carotid arteries, in particular, the temporal artery, with the involvement of the axillary, femoral and iliac arteries too. Arterial wall inflammation leads to luminal occlusion and tissue ischemia, which is responsible for the clinical manifestations of the disease. A substantial number of patients affected by GCA present head and neck symptoms, including ocular, neurological and otorhinolaryngological manifestations. The aim of this article is to present pathogenesis, clinical aspects and treatment approaches of GCA manifestations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Determine in a cohort of patients with normal hearing and chronic tinnitus if self-reported history for temporomandibular joint (TMJ) dysfunction and a positive modulation of tinnitus in the TMJ region could be suggestive of an underlying TMJ disorder., Patients and Methods: The study included 226 patients presenting to the Head and Neck Service of our University Hospital. Following audiological and somatic tinnitus evaluation, patients were divided into two groups. The study group (n = 134) included subjects that met both the following criteria: A) a self-reported history for TMJ dysfunction and B) a positive modulation of tinnitus following somatic maneuvers in the TMJ region. The control group (n = 92) included patients with similar demographic and tinnitus characteristics that did not meet the proposed criteria for somatic tinnitus. Afterwards, patients underwent clinical TMJ evaluation in the Service of Clinical Gnathology of our University., Results: One hundred thirty-one patients (57.9%) received a clinical diagnosis of TMJ disorder according to DC/TMD Axis I; 79.1% in the study group and 27.2% in the control group. Ninety-five (42.1%) patients were negative for TMJ disorders; 20.9% in the study group and 72.8% in the control group. A significantly higher number of TMJ disorders was found in patients in the study group compared to the control group (p<0.0001). Most patients had joint disorders (67.2%), followed by other (29.8%) and pain disorders (29%). Logistic regression analysis in the study group showed that female gender was more prevalent in patients with TMJ disorders., Conclusion: Our findings in patients with chronic tinnitus and normal hearing suggest that self-reported history for somatic dysfunction and modulation of tinnitus, when occurring simultaneously in the TMJ region, can be useful to preliminarily identify patients with TMJ disorders., Competing Interests: The authors have declared that no competing interests exist

There is a growing awareness that children may experience hyperacusis, a condition that is often associated with behavioral and developmental disorders. This preliminary study was aimed to investigate the effects of hyperacusis alone on various components of speech and language in children without developmental disorders. This study was conducted on 109 children aged between 4 and 7 years attending kindergarten and primary school. Hyperacusis was assessed through behavioral observation of children and questionnaires for parents. Different components of speech and language were assessed through specific tests. Hyperacusis was diagnosed in fifteen children (13.8%); ten (66.7%) were attending primary school and five (33.3%) kindergarten. A significant difference between children with and without hyperacusis was found for tests evaluating the average number of words in a sentence and phonemic fluency; older children appeared to have more difficulties. Several differences in education profiles were found: parents of children with hyperacusis spent less time with their children compared to parents of children without hyperacusis. Our preliminary results suggest some difficulties in lexical access and the use of shorter sentences by children with hypersensitivity to sound; however, the small size of our sample and the largely unknown interactions between hyperacusis and developmental disorders suggest caution when interpreting these results. Further studies on larger samples are necessary to gain additional knowledge on the effects of hyperacusis on speech and language in children without developmental disorders.

The study aimed to compare the distortion-product otoacoustic emissions (DPOAEs) with the pure-tone audiometry and to analyze the changes in participants exposed to noise. The results show a prevalence of participants with impaired DPOAEs higher than the prevalence of participants with impaired audiometries in the total sample, in men, and in outdoor workers and a prevalence of impaired DPOAEs and of impaired audiometries in men higher than in women and in outdoor workers higher than in indoor workers. The comparison of mean values between outdoor and indoor workers shows a significant difference only on some frequencies, in the DP-gram. The results suggest a higher effectiveness of DPOAEs compared with the pure-tone audiometry in identifying the presence of any damage in individuals exposed to noise at an early stage.

Objective: To evaluate olfactory function and clinical-neurological characteristics in a group of patients with mild head trauma., Methods: A total of 352 patients with MTBI underwent olfactory function evaluation. The site of head trauma, loss of consciousness <20 min, memory loss, subjective presence or absence of olfaction and other clinical, neurological and radiological aspects were evaluated and compared with the olfactory dysfunction., Results: A total of 33.5% patients enrolled in the study had an olfactory dysfunction. Eighty-seven percent of the patients had a diagnosis of anosmia whereas 13% had a diagnosis of hyposmia. Statistical analysis did not show a correlation between radiologically detected head lesions and different types of olfactory dysfunction (p > 0.05). Besides, no difference between head lesion site and different olfactory dysfunction was reported (p = 0.5). Regarding olfactory sub-tests a low detection threshold was present in these patients., Conclusion: The possibility of olfactory dysfunction should be considered in any case of MTBI appears differently than expected, a minor head injury causes anosmia much more frequently than hyposmia.

Vestibular schwannoma and endolymphatic hydrops are two conditions that may present with similar audio-vestibular symptoms. The association of the two in the same patient represents an unusual finding that may lead clinicians to errors and delays in diagnosis and clinical management of affected subjects. We discuss the case of a patient with an intrameatal vestibular schwannoma reporting symptoms suggestive for ipsilateral endolymphatic hydrops. The patient presented with fluctuating hearing loss, tinnitus, and acute rotatory vertigo episodes, and underwent a full audiological evaluation and imaging of the brain with contrast-enhanced Magnetic Resonance Imaging. Clinical audio-vestibular and radiological examination confirmed the presence of coexisting vestibular schwannoma and endolymphatic hydrops. Hydrops was treated pharmacologically; vestibular schwannoma was monitored over time with a wait and scan protocol through conventional MRI. The association of vestibular schwannoma and endolymphatic hydrops is rare, but represents a possible finding in clinical practice. It is therefore recommended investigating the presence of inner ear disorders in patients with vestibular schwannoma and, similarly, to exclude the presence of this condition in patients with symptoms typical of inner ear disorders.

Objective: Determine if somatic tinnitus patients with hyperacusis have different characteristics from those without hyperacusis., Patients and Methods: 172 somatic tinnitus patients with (n = 82) and without (n = 90) hyperacusis referred to the Tinnitus Unit of Sapienza University of Rome between June 2012 and June 2016 were compared for demographic characteristics, tinnitus features, self-administered questionnaire scores, nature of somatic modulation and history., Results: Compared to those without hyperacusis, patients with somatic tinnitus and hyperacusis: (a) were older (43.38 vs 39.12 years, p = 0.05), (b) were more likely to have bilateral tinnitus (67.08% vs 55.56%, p = 0.04), (c) had a higher prevalence of somatic modulation of tinnitus (53.65% vs 36.66%, p = 0.02) and (d) scored significantly worse on tinnitus annoyance (39.34 vs 22.81, p<0.001) and subjective hearing level (8.04 vs 1.83, p<0.001)., Conclusion: Our study shows significantly higher tinnitus modulation and worse self-rating of tinnitus and hearing ability in somatic tinnitus patients with hyperacusis versus somatic tinnitus patients without hyperacusis. These differences could prove useful in developing a better understanding of the pathophysiology and establishing a course of treatment for these two groups of patients.

The pituitary gland is an organ that functionally connects the hypothalamus with the peripheral organs. The pituitary gland is an important regulator of body homeostasis during development, stress, and other processes. Pituitary adenomas are a group of tumors arising from the pituitary gland: they may be subdivided in functional or non-functional, depending on their hormonal activity. Some trophic and neurotrophic factors seem to play a key role in the development and maintenance of the pituitary function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. Several lines of evidence suggest that trophic and neurotrophic factors may be involved in pituitary function, thus suggesting a possible role of the trophic and neurotrophic factors in the normal development of pituitary gland and in the progression of pituitary adenomas. Additional studies might be necessary to better explain the biological role of these molecules in the development and progression of this type of tumor. In this review, in light of the available literature, data on the following neurotrophic factors are discussed: ciliary neurotrophic factor (CNTF), transforming growth factors β (TGF‑β), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), vascular endothelial growth inhibitor (VEGI), fibroblast growth factors (FGFs) and epidermal growth factor (EGF) which influence the proliferation and growth of pituitary adenomas.

There is increasing evidence of a connection between hearing function and myasthenia gravis (MG). Studies of the pathophysiological basis of this relationship suggest that acetylcholine receptors (AChRs) on outer hair cells (OHCs) play a central role. In patients with MG, autoantibodies against AChRs induce a progressive loss of AChRs on OHCs, decreasing their electromotility. The stapedial reflex decay test can be altered in MG patients, and can be used as an additional tool for diagnosis and monitoring. Transient evoked and distortion product otoacoustic emissions are the main diagnostic tool for monitoring OHC functionality in MG patients, and can be used to record subclinical hearing alterations before the onset of clinically evident hearing loss. Understanding the association between MG and hearing dysfunction requires a multidisciplinary approach. Otolaryngologists should take this relationship into account when approaching patients with a diagnosis of myasthenia gravis and "in patients with MG" with ण128;œin MG patients, and the progress of hearing alterations should always be monitored in patients with MG.

Objective: The aim of this study was to evaluate the reparative role of hyaluronic acid in acute rhinosinusitis (ARS)., Patients and Methods: 48 patients affected by ARS were submitted to nasal endoscopy, nasal cytology, mucociliary transport evaluation (MCTt) and visual analogue scale questionnaire (VAS) at T0, after 14-18 days (T1) and after 30-35 days (T2). The patients were randomized into two groups, A and B, and received Levofloxacin and Prednisone. Moreover, using a nebulizer ampoule for nasal douche, Group A received high molecular weight Sodium Hyaluronate (3%) plus saline solution (NaCl 0.9%) twice a day for 30 days; Group B received saline solution twice a day for 30 days., Results: At T0 only the VAS score showed differences regarding nasal discharge and post-nasal drip. At T1, in Group A MCTt and the number of bacteria were significantly lower than in Group B. The VAS score showed improvement in Group A. At T2 in Group A, MCTt and number of neutrophils were significantly lower than in Group B. The VAS score showed statistically significant differences between the two groups regarding nasal discharge., Conclusions: In ARS patients sodium hyaluronate plus saline solution significantly improved symptoms, MCT time and reduced neutrophil count on nasal cytology.

Work-related noise exposure is one of the major factors contributing to the development of adult-onset hearing loss and tinnitus. The aim of this study was to analyze, in patients with chronic tinnitus and long-term occupational noise exposure, (A) characteristics of hearing loss, tinnitus, comorbidities, demographic characteristics and a history of work-related noise exposure and (B) differences among individuals employed in occupations with high and low risk of developing work-related noise-induced hearing loss (NIHL). One hundred thirty six patients with chronic tinnitus and at least a 10 year-long working history were divided into two groups based on the risk of their profession to induce NIHL. Individuals employed in jobs at high risk for NIHL were mostly males and exhibited a poorer hearing threshold, more evident in the left ear. Tinnitus was mostly bilateral; the next largest presentation was left-sided; patients described their tinnitus as buzzing or high-pitched. Correlation between age, length of tinnitus and worse hearing was found. Patients with a higher degree of hearing impairment were mostly males and were more likely to have a family history of hearing loss and at least one cardiovascular comorbidity. Our study shows some differences in individuals with tinnitus and a history of a profession associated with increased exposure to NIHL compared to those without such a history., Competing Interests: The authors declare no conflict of interest.