Hearing loss is the most common sensory deficit in the elderly, and it is becoming a severe social and health problem. Especially in the elderly, hearing loss can impair the exchange of information, thus significantly impacting everyday life, causing loneliness, isolation, dependence, and frustration, as well as communication disorders. Due to the aging of the population in the developed world, presbycusis is a growing problem that has been reported to reduce quality of life (QoL). Progression of presbycusis cannot be remediated; therefore, optimal management of this condition not only requires early recognition and rehabilitation, but it also should include an evaluation of QoL status and its assessment.

The obstructive sleep apnea syndrome (OSAS) represents only part of a large group of pathologies of variable entity called respiratory sleep disorders (RSD) which include simple snoring and increased upper airway resistance syndrome (UARS). Although the etiopathogenesis of adult OSAS is well known, many aspects of this syndrome in children are still debated. Its prevalence is about 2% in children from 2 to 8 years of age, mostly related to the size of the upper airways adenoid tissue. Several risk factors linked to the development of OSAS are typical of the pediatric age. The object of this paper is to analyze the state of the art on this specific topic, discussing its implications in terms of diagnosis and management.

Autoimmune inner ear disease (AIED) has been defined as a condition of bilateral sensorineural hearing loss (SNHL), caused by an ‘uncontrolled’ immune system response. The inner ear can be the direct target of the immune response, but it can be additionally damaged by a deposition of circulating immune complexes or by systemic immune-mediated diseases. The clinical expression of immune-mediated inner ear disease shows a progressive bilateral and asymmetric SNHL profile, which typically benefits from a steroid and immunosuppressive therapy. The onset of AIED is between 3 and 90 days. Cochlear symptoms can be associated with vestibular disorders and in 15%–30% of cases, AIED occurs in the contest of a systemic autoimmune disease. Currently, the onset of immune-mediated SNHL is not a well-understood process and the pathogenetic mechanisms of AIED remain unclear. Furthermore, there are no standardized diagnostic criteria or reliable diagnostic tests for the diagnosis of AIED. Hence, the definition of immune-mediated cochleovestibular disorders is a challenging diagnosis based on exclusion. A close collaboration between otolaryngologists, audiologists and rheumatologists is recommended, in order to achieve the multidisciplinary management of this rare entity, since an early AIED identification and a prompt medical treatment might result in acceptable hearing outcomes. The paper describes the clinical features of AIED and offers a diagnostic flow-chart to use in the clinical assessment of this condition.

SUMMARYOSA is a condition characterised by episodes of complete or partial obstruction of the upper airway, associated with blood-gas changes and atypical sleep patterns. Early diagnosis of OSA may reduce the occurrence of systemic complications over time, although the diagnosis of OSA is, unfortunately, often late. The aim of the work is to review the current concepts in evaluation of paediatric obstructive sleep apnoea (OSA), with an updated revision of the literature considering risk factors, clinical manifestations, and basic and advanced assessment in the paediatric population. For this narrative review, PubMed, Embase and Cinahl databases were searched for the last 10 years, according to PRISMA criteria/guidelines. Assessment of paediatric OSA remains challenging and paediatric patients should always be carefully evaluated; polysomnography is the gold standard for diagnosis of paediatric OSA.

In this study we have inhibited the expression of two negative regulators of chondrogenesis, Slug transcription factor (TF) and the small non-coding single stranded RNA microRNA-221 (miR-221), in human mesenchymal stem cells (MSCs). Our aim was test a new approach to guide the cells toward a chondrocyte - like phenotype, without the employment of differentiating agents, in the prospect of their clinical applications for cell-based cartilage tissue engineering. We have characterized these manipulated cells by gene expression analysis at the RNA and protein levels. We demonstrated that decreased miR-221 or Slug induced an increase of chondrogenic markers, including collagen type II (Col2A1), and the positive chondrogenic TFs Sox9 and TRPS1. Slug and TRPS1 are not direct targets of miR-221 since their expression was not affected by miR-221 content. Further, we showed by gene expression and Chromatin Immunoprecipitation analyses that i. miR-221 is positively regulated by Slug in hMSCs, where Slug and miR-221 high levels hamper cell differentiation, and ii. TRPS1 contributes to maintaining low levels of miR-221, both in hMSCs committed toward chondrogenesis by Slug depletion and in chondrocytes, where the low levels of miR-221 and Slug allow a chondrogenic phenotype.Taken together, our data may be relevant both to understand yet unknown miRNA - TF regulatory loops in cartilage biology and to establish new strategies based on a siRNA approach for cartilage tissue engineering.

To describe the audio-vestibular disorders related to the newly SARS-CoV-2 infection, including the possible ototoxicity side-effects related to the use of drugs included in the SARS-CoV-2 treatment protocols. A systematic review was performed according to the PRISMA protocol. The Medline and Embase databases were searched from March 1, 2020 to April 9, 2021. Initially the search yielded 400 manuscripts, which were reduced to 15, upon the application of inclusion criteria. Sensorineural hearing loss (SNHL) is the most frequent audio-vestibular symptom described, occurring alone or in association with tinnitus and vertigo. The etiopathogenesis of the inner ear disorders related to COVID-19 infection is still poorly understood. The number of reports of COVID-19 infections associated to audio-vestibular disorders is increasing; even if the quality of the studies available is often insufficient, audio-vestibular disorders should be considered as possible manifestations to be included among the symptoms of this infection.

Background: To investigate the presence of laryngopharyngeal reflux in patients with obstructive sleep apnea (OSA) employing the salivary pepsin concentration method. To compare the results of pepsin concentration with the severity of the pathology. Methods: Seventy-five OSA patients (44 males, 31 females) were enrolled in the study. For each patient, the AHI (apnea–hypopnea index) and the BMI (body mass index) were initially evaluated. All the patients enrolled were assessed using the reflux symptom index (RSI) and the reflux finding score (RFS) in order to perform a clinical diagnosis of laryngopharyngeal reflux. In all patients a salivary sample was taken to estimate the presence of pepsin and its concentration. Results: The incidence of LPR (laryngopharyngeal reflux) in OSA patients, evaluated using the salivary pepsin concentration test (PEP-test), was found to be 32% of cases. Linear regression testing did not show any correlation between AHI and pepsin concentration in salivary samples (p = 0.1). Conclusion: A high number of patients with OSA seem to show positivity for salivary pepsin, correlated to an LPR. There does not appear to be a correlation between the severity of apnea and the grade of salivary pepsin reflux. On the other hand, direct correlation between BMI and the value of pepsin in salivary specimens was observed.

Background. Previous studies reported human papillomaviruses (HPVs) in middle ear tumors, whereas these viruses have been poorly investigated in chronic inflammatory middle ear diseases. We investigated HPVs in non-tumor middle ear diseases, including chronic otitis media (COM). Methods. COM specimens (n = 52), including chronic suppurative otitis media (CSOM) (n =38) and cholesteatoma (COMC) (n = 14), as well as normal middle ear (NME) specimens (n = 56) were analyzed. HPV sequences and DNA loads were analyzed by quantitative-PCR. HPV genotyping was performed by direct sequencing. Results. HPV DNA was detected in 23% (12/52) of COM and in 30.4% (17/56) of NME (p > 0.05). Specifically, HPV DNA sequences were found in 26.3% (10/38) of CSOM and in 14.3% (2/14) of COMC (p > 0.05). Interestingly, the HPV DNA load was higher in COMC (mean 7.47 copy/cell) than in CSOM (mean 1.02 copy/cell) and NME (mean 1.18 copy/cell) (P = 0.03 and P = 0.017 versus CSOM and NME, respectively). HPV16 and HPV18 were the main genotypes detected in COMC, CSOM and NME. Conclusions. These data suggest that HPV may infect the middle ear mucosa, whereas HPV-positive COMCs are associated with higher viral DNA loads as compared to NME.Pathogens 2020, 9, 224 2 of 10 mucosa sampled from CSOM patients [11]. However, the etiology of CSOM remains to be determined. The relationship between HPV infection and inflammation has been previously reported [12]. It has been shown that persistent infection with high-risk HPVs leads to an increase in pro-inflammatory cytokines, including IL-6, TNF-α and MIP-1α [13]. In addition, high-risk HPV type 16 (HPV16) is able to increase the expression of cyclooxygenase-2 (COX-2), a key enzyme in the synthesis of prostaglandins, which are important mediators of inflammation [14,15]. Until now, only a single study has reported HPV DNA sequences in CSOM, whereby different HPV genotypes, including HPV16, HPV18 and HPV6, have been detected in 30.7% of CSOM [4].COMC is a form of expanding growth consisting of keratinizing squamous cell epithelium [16]. There is great interest in the etiopathogenesis of HPV-associated cholesteatoma because HPV commonly infects the stratified epithelium [17,18]. However, conflicting data have been reported for HPV in COMC [10,[19][20][21]. HPV sequences have been detected in COMC with different prevalence, ranging from 3% to 70% [10,[19][20][21]. Moreover, no specific HPV genotypes have been associated with COMC, as high-and low-risk HPVs, such as HPV16, HPV18 and HPV6 and HPV11, have been detected [10,[19][20][21].There is emerging evidence that HPV infection can occur in different anatomical sites. Since HPV infects epithelia [22], all anatomical sites covered with epithelial tissue are potentially exposed to HPV infection. Apart from pluristratified tissues of the cervix [23], vulva [24] and oral pharynx [25], HPV sequences have been detected in simple epithelia from several anatomical sites such as lung [26], upper respiratory tract [27], larynx [28] and nose [29]. Since the middle ear muc...