Cancer stem cells-driven tumor growth and immune escape: the Janus face of neurotrophins

Cancer Stem Cells (CSCs) are self-renewing cancer cells responsible for expansion of the malignant mass in a dynamic process shaping the tumor microenvironment. CSCs may hijack the host immune surveillance resulting in typically aggressive tumors with poor prognosis. In this review, we focus on neurotrophic control of cellular substrates and molecular mechanisms involved in CSC-driven tumor growth as well as in host immune surveillance. Neurotrophins have been demonstrated to be key tumor promoting signaling platforms. Particularly, Nerve Growth Factor (NGF) and its specific receptor Tropomyosin related kinase A (TrkA) have been implicated in initiation and progression of many aggressive cancers. On the other hand, an active NGF pathway has been recently proven to be critical to oncogenic inflammation control and in promoting immune response against cancer, pinpointing possible pro-tumoral effects of NGF/TrkA-inhibitory therapy. A better understanding of the molecular mechanisms involved in the control of tumor growth/immunoediting is essential to identify new predictive and prognostic intervention and to design more effective therapies. Fine and timely modulation of CSCs-driven tumor growth and of peripheral lymph nodes activation by the immune system will possibly open the way to precision medicine in neurotrophic therapy and improve patient's prognosis in both TrkA- dependent and independent cancers

Obstructive sleep apnea syndrome in the pediatric age: the role of the otorhinolaryngologist

OBJECTIVE: Obstructive sleep apnea (OSA) is the primary indication for tonsillectomy, one of the most common pediatric surgical procedures, commonly performed in association with adenoidectomy. The objective of this review article is to evaluate the role of the otorhinolaryngologist in pediatric OSA. MATERIALS AND METHODS: A literature review has been performed on the following topics: peculiarities of sleep-disordered breathing in pediatric age; discrimination of sleep disorders; adenotonsillar hypertrophy; surgical techniques; adjuvant surgical procedures. RESULTS: The role of the otorhinolaryngologist in pediatric OSA is important for the evaluation of the upper airways and of essential biometric and polysomnographic data and for indication and execution of appropriate surgical treatment. In the majority of healthy children, adenotonsillectomy for OSA results in a dramatic improvement in respiratory parameters as measured by polysomnography. When post-surgical residual OSA occurs, it is essential to monitor patients by means of drug-induced sleep endoscopy (DISE). CONCLUSIONS: Otolaryngologic assessment is of paramount importance to correctly classify a child with OSA. Correct inspection of the upper airway and quantification of the quality of sleep through polysomnography lead to the right therapeutic choice. Knowledge of different surgical techniques helps to deal with residual OSA after studying the obstruction sites by drug-induced sedation endoscopy

Recurrence of non-hydropic sudden sensorineural hearing loss (SSNHL): a literature review

Sudden Sensorineural Hearing Loss (SSNHL) is typically defined as the acute onset (less than 3 days) of a perceptive hearing loss of more than 30dB over at least three contiguous frequencies on pure tone audiometry. The exact incidence of SSNHL is uncertain, since many patients have a rapid and spontaneous resolution of symptoms and therefore don’t reach medical attention. Estimate of incidence ranges from 5 to 20 per 100.000 individuals, and bilateral involvement is very rare; it increases in the older patients (>65 yo)(77 per 100.000) the in younger population (<18 yo)(11 per 100.000) [3]. The true incidence of paediatric SSNHL is not established in literature; 40% of examined child with SSNHL, showed anatomic abnormaliti

Sub-clinical effects of chronic noise exposure on vestibular system

Aim: to investigate the effect of chronic noise exposure on vestibular function of subjects without clinical evidence of vestibular disorders and with documented cochlear damage from noise. Subjects and methods: 25 patients with chronic noise- induced hearing loss (NIHL) and without vestibular complaints (group A) and 25 matched controls with sensorineural hearing loss without noise exposure (group B), underwent audiological and vestibular test including caloric and cervical vestibular-evoked myogenic potentials tests (cVEMPs). Results: In subjects chronically exposed to noise, similarly to that of the auditory threshold, an increase in the evocation threshold of VEMPs has been documented, statistically significant (p<0,05) and independent of the performance of the auditory threshold. p1-n1 amplitude values showed a significant difference between group A and group B. No significant difference for p1-n1 latencies between the two groups was found. Conclusion: We have documented the possibility of vestibular lesion, along with cochlear damage, related to chronic acoustic trauma

Neuroinflammatory markers in the serum of prepubertal children with down syndrome

Down Syndrome (DS) is the most common chromosomal disorder. Although DS individuals are mostly perceived as characterized by some distinct physical features, cognitive disabilities, and cardiac defects, they also show important dysregulations of immune functions. While critical information is available for adults with DS, little literature is available on the neuroinflammation in prepubertal DS children. We aimed to evaluate in prepubertal DS children the serum levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), oxidative stress as free oxygen radicals defense (FORD), free oxygen radicals test (FORT), and cytokines playing key roles in neuroinflammation and oxidative processes as TNF-, TGF-β, MCP-1, IL-1, IL-2, IL-6, IL-10, and IL-12. No differences were found in NGF between DS children and controls. However, BDNF was higher in DS subjects compared to controls. We also did not reveal changes in FORD and FORT. Quite interestingly, the serum of DS children disclosed a marked decrease in all analyzed cytokines with evident differences in serum cytokine presence between male and female DS children. In conclusion, the present study evidences in DS prepubertal children a disruption in the neurotrophins and immune system pathways

Sudden olfactory loss as an early marker of COVID-19: a nationwide Italian survey

Purpose: The presence of many asymptomatic COVID-19 cases may increase the risks of disease dissemination, mainly for physicians. There are numerous reports on the frequent findings of sudden anosmia or hyposmia, before or at the same time of the typical COVID-19 symptoms onset. The aim of this study was to verify the association of olfactory impairment and COVID-19, providing a basis for subsequent research in the field of COVID-19 clinical heterogeneity. Methods: We developed a 15-item online questionnaire on “Sudden Olfactory Loss (SOL) and COVID-19” that was administered during March 2020 to Italian general practitioners registered to a social media group. Results: One hundred and eighty responses were received. SOL was identified as a significant sign of infection in COVID-19 patients, mainly aged between 30 and 40 years, even in the absence of other symptoms. SOL was present as an initial symptom in 46.7% of subjects, and in 16.7%, it was the only symptom. Among the COVID-19 confirmed cases, SOL occurred as the only symptom in 19.2% of patients. Conclusion: SOL could represent a possible early symptom in otherwise asymptomatic COVID-19 subjects. Subjects affected by SOL should be considered as potential COVID-19 cases. Level of evidence: 4

Teaching and learning in a multilingual Europe: findings from a cross-european study

School classrooms within the EU are multilingual learning environments. The diversity of pupils in classrooms raises significant challenges for teachers, but to date, there are no data from large-scale surveys that compare views within and across European countries. A bespoke questionnaire was designed to examine views of current classroom learning environments with respect to the multilingualism. The questionnaire was piloted and subsequently completed by 2792 teachers across different European countries. Eleven countries provided sufficient data for analyses. Results from structural equation model- ling showed that teachers’ attitudes could be reliably measured across Europe with the use of carefully devised questionnaire, whose loading and factor structure remained invariant across countries. Teachers’ views about multilingualism were most challenged by the numbers of children in their classes, not the percentage of multilingual pupils in the class. Countries differed in how they perceived multilingualism, with their differences leading to distinctive country clusters. Gender and education level (elementary vs. secondary) differences were also observed irrespective of country. These findings enhance our understanding of the role that the characteristics of teachers and their classrooms play in a multilingual setting across diverse European settings. The practical relevance of the results and new opportunities for teacher training are discussed