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.

(word count: 246245) 1Background: Asthma and other Th2 inflammatory conditions have been associated with increased 2 susceptibility to viral infections. The mechanisms by which Th2 cytokines can influence immune 3 responses to infections are largely unknown. 4 Methods:We measured the effects of Th2 cytokines (IL-4 and IL-13) on bronchial epithelial cell 5 innate immune antiviral responses by assessing interferon (IFN-β and IFN-λ1) induction following 6 rhinovirus (RV)-16 infection. We also investigated the modulatory effects of Th2 cytokines on 7 signalling pathways involved in the rhinovirus-induced interferon production and inflammatory 8 cascade including Toll-like receptor (TLR)-3, interferon-responsive factor (IRF)-3, and nuclear 9 factor (NF)-kB., i.e. key molecules and transcription factors involved in the rhinovirus-induced 10 interferon production and inflammatory cascade. Pharmacological and redox modulation by the 11 reducing agent N-acetylcysteine onof these pathways was also testedassessed. 12Results: Th2 cytokines impaired RV16-induced interferon production, increased rhinovirus 13 replication and impaired TLR3 expression in bronchial epithelial cells. These results were 14 replicated in vivo: we found increased IL-4 mRNA levels in nasal epithelial cells from nasal 15 brushing of atopic rhinitis patients and a parallel reduction of TLR3 expression and increased RV16 16 replication compared to non-atopic subjects. Mechanistically, Th2 cytokines impaired RV-16 17 induced activation of IRF3, but had no effects on RV16-induced NF-kB activation in bronchial 18 epithelial cell cultures. N-acetylcysteine and phosphoinositide 3-kinase (PI3k) inhibitor restored the 19 inhibitory effects of Th2 cytokines over RV-16 induced activation of IRF3 and production of IFNs. 20Conclusions: IL-4 and IL-13, through inhibition of TLR3 expression and oxidant-mediated 21 inhibition of signalling ), impair immune response to RV-16 infection. These data suggest 22 that Th2 conditions increase susceptibility to infections and identify a pharmacological 23 approachapproaches with potential to restore impaired immune response in these conditions. 24Page 3 of 63 Allergy 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Asthma is a chronic disorder of the airways that is typically inflammatory in nature and 3 affects millions of children and adults (1). (1). 4Viral infections of the respiratory tract early in life are associated with an increased risk of 5 developing asthma later in life and are also the most frequent causes of asthma exacerbations in 6 both children and adults (2). Rhinoviruses are the respiratory virus type that is most frequently 7 detected during asthma exacerbations (3). The innate immune response is at the forefront of the 8 defence against respiratory infections. Impaired innate immune responses have been reported to be 9...

The tumor-suppressor protein p53 is over-expressed in a large fraction of squamous-cell carcinomas of the larynx (LSCCs). p53 overexpression is dependent upon the synthesis of mutated versions of the protein and has been associated with the malignant progression of certain tumor types. In order to examine the prognostic value of p53 immunodetection in LSCCs, we performed a retrospective analysis on a selected series of tumors, using the PAb 1801 and CM1 antibodies. No significant difference in the frequency of p53 over-expression was observed between tumors from patients with early relapse (67%) and those who had been disease-free for more than 5 years (84%). The lack of correlation of p53 immunoreactivity with clinical stage and differentiation grade of LSCCs, together with the coordinated expression of p53 in primary tumors and the corresponding lymph-node metastases, indicate that p53 over-expression is probably unrelated to the biological aggressiveness of these tumors. In addition, the detection of p53 immunostaining in pre-invasive areas as well as in preneoplastic lesions suggests that p53 abnormalities probably constitute a very early event in LSCC development.

The histologic variety of parotid gland carcinomas, their different natural history, and the peculiar anatomy of the parotid region can make prognosis and therapeutic strategy quite controversial. The present study was designed to evaluate those prognostic factors able to affect the long-term results in a group of 167 consecutively treated parotid epithelial malignancies. The continuous or discrete covariants considered as potential prognostic factors are age, sex, histotype, grading, TNM and pTNM classification, facial nerve involvement, type of surgery on the tumor site and on nodes, facial nerve resection, and postoperative radiotherapy. All the material has been statistically analyzed and the results have been compared with the principal data published. According to the analysis, the most relevant prognostic factors in parotid gland carcinomas appear to be pTN staging, tumor grading, facial nerve involvement, and local extension. These factors could reliably predict the patient's chance for survival, and thus influence the therapeutic strategy.

The coronavirus disease 2019 (COVID-19) pandemic has put a substantial burden on the Italian healthcare system, resulting in the restructuring of hospitals to care for CO-VID-19 patients. However, this has likely impacted access to care for patients experiencing other conditions. We aimed to quantify the impact of COVID-19 on access to care for patients with urgent/emergent urological conditions throughout Italy. Materials and Methods: A questionnaire was sent to 33 urological units in the AGILE consortium, asking clinicians to report on the number of urgent/emergent urological patients seen and/or undergoing surgery over a 3-week period during the peak of the COVID-19 outbreak and a reference week prior to the outbreak. ANOVA and linear regression models were used to quantify these changes. Results: Data from 27 urological centres in Italy showed a decrease from 956 patients/week seen just prior to the outbreak to 291 patients/week seen by the end of the study period. There was a difference in the number of patients with urgent/emergent urological disease seen within/during the different weeks (all p values < 0.05). A significant decrease in the number of patients presenting with haematuria, urinary retention, urinary tract infection, scrotal pain, renal colic, or trauma and urgent/emergent cases that required surgery was reported (all p values < 0.05). Conclusion: In Italy, during the COVID-19 outbreak there has been a decrease in patients seeking help for urgent/emergent urological conditions. Restructuring of hospitals and clinics is mandatory to cope with the COVID-19 pandemic; however, the healthcare system should continue to provide adequate levels of care also to patients with other conditions.