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In the context of the global COVID-19 pandemic, companies and institutions all over the world are trying to find the best ways to reorganize their activity, minimizing the contagion risk among their employees, so as to protect their health and prevent internal SARS-COV-2 outbreaks. The recent development of new communication technologies, such as smartphones and tablets, has paved the way for the development and implementation of different applications. Starting with the above issues, in this study, we wanted to investigate the efficacy of iAudiometry application developed by our research team for the detection of deficits in the auditory system. Furthermore, we analyzed the precision in detecting ambient Sound Pressure Levels between 3 different types of headphones. To this aim we divided the study and development process into four main phases: the feasibility study; the development of a signal generation algorithm, calibration and evaluation of the ambient Sound Pressure Level (SPL) on different types of headphones, and; a comparative study between conventional audiometry and an app with related headphones. Finally, this study allowed us to differentiate the headphones tested into 3 different types: headphones suitable for professional screening; Bluetooth headphones suitable for professional screening, and; headphones with slight but statistically significant differences, not suitable for professional screening. Our App is able to easily reproduce a reliable audiometric screening, limiting the contact between patient and examiner.

Sudden sensorineural hearing loss is a common and alarming symptom of about 360 million people that suffer from hearing impairment worldwide. The sudden sensorineural hearing loss usually arises unilaterally and it is habitually described as greater than 30dB hearing reduction, attributable to lesions of the cochlea, cranial nerve VIII, brainstem and temporal lobe. There are many factor that promote the onset of this lesions such us infections, circulatory diseases, inner ear neoplasia and neurological disorders. This pathology is characterized by primary symptoms such as the impairment of the comprehension of spoken language and the struggling to listen to music. Subsequently, secondary symptoms arise as well as anxiety, inadequate coping with illness and psychosomatic disturbances that have a negative impact on patients with a significant reduction in the quality of life. Treatment of the sudden sensorineural hearing loss remains one of the most problematic issues for contemporary otorhinolaryngology, because of the wide array of the presumed mechanisms that underpin this disorder. Although the pharmacological treatment remain even now empirical and the management is not standardized in term of medical treatment, duration and route of administration, different agents are used. In the past, pharmacological approaches have included antiviral agents, vitamin, herbal preparations, carbogen inhalations or magnesium, administered on either an inpatient or outpatient procedures. Nowadays, the corticosteroids therapy remains the mainstay strategy, but considering the multifaceted aspects of this disorder, diuretics, anticoagulants, vasodilatators and fibrinolityc agents have also been tried. In this chapter, we will focus mainly on the principal pharmacological approaches of the sudden sensorineural hearing loss that will be described and examined in terms of mechanism of action and effectiveness.

In this study we explored the effect and the biological action of synthesized benzamido derivatives bearing the (1S,2S)-2-phenyl-cyclopropane-1-carboxamido, 1,1'-biphen-2-carboxamido and 1,1'-biphen-4-carboxamido moieties on K562, a human leukemia cell line. Among the synthesized compounds a particular antiproliferative action was observed with the benzamido derivative bearing the 2-1,1'-biphenyl moiety with the substitution at the 5 position of the benzamido moiety with iodine. This compound showed cytotoxic effects in K562 leukemic cells at nanomolar concentrations and was, therefore, chosen as compound to explore its mode of action. Our analyses provided evidence that this benzamido derivative induced a reduction in cell number and volume with the appearance of a shrunken cytoplasm at 24h, followed by a widespread cell fragmentation at 48h. As demonstrated by flow cytometry analyses, the effect was dose- and time-dependent, causing a G2/M cell cycle arrest in the first phase of treatment (24h), followed by an apoptotic death at 48h (IC50 0.5 μM ). The elucidation of the underlying mechanism also disclosed that DNA arrest in G2/M phase of cell cycle was consequent to DNA lesions, since an increase in phospho-ATM and yH2AX, two known markers of DNA repair response system, was observed. Prolonging the time of treatment, the effects, which were observed only in leukaemic cells but not in normal bronchial epithelial cells, were accompanied by ROS production, JNK phosphorylation and induction of a caspase-dependent apoptosis.

Tinnitus is not a disease, but rather a symptom or condition characterized by a conscious perception of an unreal sound in the absence of external auditory stimulus. This ontological condition can modify everyday life in different ways: causing distress and annoyance, sleep disruption, anxiety and depression. The World Health Organization (WHO) describes tinnitus as a symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, grinding, hissing, roaring or other noises in the ear. Even if different treatments exist for “tinnitus-related abnormalities” such as cognitive behavioural therapy and/or sound therapy, no effective pharmacological approach is available, although much research is underway into the mechanism and possible treatments. Furthermore, no drugs are currently approved by the FDA for treatment of spontaneous idiopathic tinnitus, and few drugs reliably suppress or eliminated chronic tinnitus in the majority of patients. A large number of researches have been conducted to evaluate the efficacy of different classes of drugs in alleviating the symptoms of tinnitus. Tricyclic antidepressant, selective-serotonin-reuptake inhibitors, benzodiazepine, anticonvulsant agents, local anesthetics, diuretics, anticoagulants and vasodilators are just some of the drugs that have been taken into account to improve the quality of life and reduce awareness of-and reaction to-tinnitus. In this chapter, current evidence on emerging pharmacological approaches to tinnitus will be described and examined in terms of mechanism of action and effectiveness.

The effects of alcohol have been widely studied during the past century as alcohol abuse is a major health problem in Western society. In the last years, a growing body of evidence indicates that acetaldehyde, the first oxidation product of ethanol, is one of the mediators of peripheral and central effects of ethanol. Indeed, acetaldehyde has been recently taken into account as the mediator of the rewarding properties of alcohol. The role of acetaldehyde in ethanol-related properties has been proved by enzymatic manipulation studies in which the inactivation of acetaldehyde potentially synthesized in the brain produces the same results as blocking the formation of acetaldehyde by inhibiting brain catalase activity. Moreover, electrophysiological and pharmacological analyses showed that acetaldehyde is able to stimulate dopamine release in the nucleus accumbens through enhancement of firing rate, spikes/burst, and burst firing of ventral tegmental neurons. Thus, the aim of this review is to summarize latest results on the role of acetaldehyde as the mediator of ethanol-central effects.

Le cinnammido benzammidi rappresentano una classe di sostanze biologicamente attive di grande interesse farmaceutico. Nonostante siano state descritte per svariate attività biologiche, nessun dato è stato riportato sulla loro attivita antitumorale. Inizialmente una serie di 2-cinammidobenzammidi variamente sostituite sono state sintetizzate e valutate per la loro attività antiproliferativa. Partendo dal derivato risultato più attivo, il 2-cinnammido-5-iodobenzammide, che ha mostrato una percentuale di inibizione della crescita sulle K562 del 74% a 10μM, sono stati sintetizzati una serie di derivati al fine di approfondirne la SAR.I composti così ottenuti sono risultati attivi nei confronti di numerose linee cellulari tumorali a concentrazioni micromolari e submicromololari inducendo un blocco del ciclo cellulare delle K562 in fase G2M. Inoltre i derivati sintetizzati sono in grado di indurre apoptosi nelle cellule HEP G2.

3,4-diphenylisoxazolo[3,4-d]pyridazin-7(6H)-one analogs were synthesized and tested for the antiproliferative activity. Study on the cell cycle alteration and on some cellular target (ATM, procaspase-2 proteins and H2AX histone) demonstrate the increase of the cell population in S phase and to induce cellular death by apoptosis by DNA damage with double strand breaks.

The effects of alcohol have been widely studied during the past century, corroborating the idea that this tiny chemical compound acts throughout most of our neurotransmitter systems since it is capable of inducing addictive behaviour. Two of the most serious problems of alcohol addiction are craving and relapse; several studies have demonstrated that relapse is related to the anxious state which occurs during withdrawal, and it has been proved that this behavioural modifications results from an alteration of the dopaminergic and serotonergic systems. An important role in the neurobiology of alcohol addiction is played by acetaldehyde (ACD), ethanol first metabolite. Our recent studies indeed, have demonstrated that ACD itself is able to induce CRH release from hypothalamic explants, underlying the central role played by ACD in alcohol-induced modifications of the HPA axis. Moreover, for the first time, this group has shown that ACD is able to induce and maintain an operant drinking behaviour after repeated abstinence periods, and in the presence of a conflict situation in rats, mimicking the same characteristics as alcohol. ACD is produced either peripherally or within the brain by alcohol dehydrogenase and catalase, respectively. Studies assert that the highest concentrations of catalase in the brain are mainly located in aminergic neurons suggesting that ACD could take part in alcohol action in those circuitries. Further investigations are then necessary to fully understand the molecular mechanisms underlying the neurochemical and behavioural modifications induced by ACD, as a mediator of alcohol activity in the brain., peer-reviewed

The new ring system pyrazolo[3,4-c][1,5]benzodiazocine was obtained through cyclization of the key intermediate of type 6a-d and 9, in refluxing toluene in presence of a catalytic amount of p-toluensulfonic acid, from moderate to high yields

Early exposure to stressful stimuli is crucial for developing varied behavioural patterns in adulthood such as anxiety, cognitive dysfunction and abuse disorders. The alteration of the hypothalamic–pituitary–adrenal (HPA) axis represents the neurobiological substrate responsible of the behavioural consequences of prenatal stress (PS). Indeed, prenatal manipulation of the HPA axis impacts on cognitive performance of the adult offspring, but also on vulnerability to alcohol consumption. Prenatal acute, moderate restraint stress has proved to facilitate HPA axis development of the offspring, since maternal corticosterone secretion leads to the reduction of anxiogenic behaviour and an improvement in the ability to cope with stress, increasing both the rate of learning and long-term potentiation, but also gestational stress blunts initial alcohol-induced HPA axis activation. In our recent study, moderate alcohol intake proved to reduce emotionality and facilitate the adaptive responses to stress, enhancing behavioural flexibility. Based upon these findings, we aimed at assessing the impact of a single, intense prenatal stress on exposure to alcohol preference and on the effects exerted by ethanol on behavioural reactivity, anxiety-like behaviour and spatial learning in adult male Wistar rats.

Respiratory tract infections are the most common diseases in childhood. The respiratory tract, widely branched system of ducts, is particularly exposed to the action of microorganisms transmitted by air from here the high frequency of infections they face especially in the first years of life. It is usual distinguish: upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI). In particular, in infections of the upper airways, the inflammatory process, result of the interaction between microbes and the immune response, can be localized to the mucosa of the nose or sinuses (common cold and sinusitis), or the pharynx or larynx (pharyngotonsillitis and laryngitis) and it has predominantly a viral etiology although occasionally it may be followed by bacterial complications such as otitis media. The aim of the following article is the description of these different clinical pictures, highlighting the clinical and epidemiological features and current management guidelines.

Introduction: To examine the putative association between Sleep-Disordered breathing and hearing disorders Material and methods: 120 Sicilian subjects ranging from 14 to 85 years of age who were divided in 46 cases suffering from tinnitus (G1 group) and 74 controls (G2 group) were evaluated through STOP BANG screening questionnaire and Four-Variable Screening Tool; after Data collecting each subject underwent Audiological assessment by multi-frequency audiometry (PTA) and Transient-evoked otoacoustic emissions (TEOAE-diagnostic) for each ear. Results: Cases showed: PTA significantly severe than the control group (58.70% vs. 16.89% hearing loss; P

Infants admitted to the neonatal intensive care unit (NICU), who represent the 4-8% of all births, present problems such as prematurity, low Apgar scores, infections, hyperbilirubinemia and hearing impairment. In particular significant hearing loss is the most common disorder at birth, occurring in 1 to 2 newborns per 1000 in the general population and 24% to 46% of newborns who are admitted to a NICU. This leads more difficulty to develope verbal skills (learning vocabulary, grammar, word order and idiomatic expressions), language, learning and speech. Hearing impairment influences also cognitive and affective development of infants making consequences in their interpersonal relationships. Joint Committee on Infants Hearing (JCIH) identified many risk factors in NICU infants like as prolonged mechanical ventilation, asphyxia, low birth weight and ototoxic medication and therefore the first step for early diagnosis of hearing loss is identify these factors. Second step is to plan a correct screening strategy. Screening procedures to detect hearing impairment may be divided into two categories: behavioral and electrophysiological. Behavioral techniques produce a high number of false-negative results due to the relative subjectivity of the assessment and difficulty in detecting mild or unilateral hearing loss. Electrophysiological procedures have greater sensitivity and specificity and include measuring the following: auditory brainstem responses (ABR), automated auditory brainstem responses (AABR), and evoked otoacoustic emissions (EOAE). In this chapter will analyze the prevalence of the risk factors in NICU infants most often associated with hearing loss and the screening methods to arrive as soon as possible an early diagnosis.

In un precedente lavoro abbiamo mostrato i risultati relativi alla sintesi ed all’attività biologica del CF3-TZP 1[1] (Figura 1). Le attività antiproliferativa e apoptotica del composto 1 sono state testate su differenti linee cellulari, HL60 sensibili, HL60-R (MDR), K562 e K562-R (resistenti al Gleevec®), mostrando un profilo di attività biologica similare sulle cellule sensibili e resistenti nel range di 21-40 µM per l’IC50 e 36-62 µM per l’AC50. L’analisi citofluorimetrica sulle K562 sensibili ha indicato che il composto 1 determina un arresto dose-dipendente del ciclo cellulare in fase G0-G1 nelle prime 24 h di trattamento, mentre nelle successive 24 h si è notato una riduzione del picco G0-G1 ed un incremento del picco apoptotico subG0-G1. Gli incoraggianti risultati biologici ci hanno spinto a continuare gli studi su questa tipologia di molecole sintetizzando l’isostero 2 (Figura 1) attraverso una lunga via di sintesi (15 steps). Attualmente, sono in corso i saggi biologici per valutare le attività antiproliferativa e apoptotica. Bibliografia 1 Maggio, B.; et al, Eur. J. Med. Chem., 2008, 43, 120.

Newborn babies who need intensive medical care are often sheltered into a special area of the hospital called Neonatal Intensive Care Unit (NICU). In this structure, babies are regularly subject to conditions that would be considered harmful by older children and adults. In the last years, many clinical researches have paid particular attention to effectiveness of various pharmacological therapies, regularly used in neonatal intensive care that have sharply reduced mortality of newborn and preterm infants. Although there are many classes of drugs used for the treatment of different diseases (sepsis, pain, seizures, pulmonary hypertension and infection), the fledgling population is more difficult to handle because there are many physiological changes that happen in infants which do not occur at any other time of life. Furthermore, there are many drugs used during the first stage of life, able to induce various toxic effects on the principal organs and apparatus. For example, there are many relationships between amikacina serum levels and central conduction time in brainstem auditory evoked potentials within therapeutic range levels in newborns as index of drug toxicity in brainstem auditory centers in neonatally exposed infants. In this chapter, we will focus mainly on the principal pharmacological strategies used for dealing with neonatal diseases in the Neonatal Intensive Care Unit.

I chinazolinoni sono composti eterociclici azotati che, insieme alle chinazoline, rappresentano degli importanti farmacofori in possesso di un ampio spettro di proprietà biologiche tra cui quella antitumorale. Recentemente sono stati riportati in letteratura dei derivati 4-chinazolinonici in grado di inibire in vitro l’enzima diidrofolato reduttasi (DHFR) con IC50 comprese tra 0.4 e 1.0 µM [1]. Allo scopo di progettare la sintesi di nuovi potenziali inibitori della DHFR, è stato condotto uno studio di modellistica molecolare considerando tale enzima come biotarget. Tale studio ha portato alla selezione di 42 nuovi derivati 4-chinazolinonici (Figura 1). Attualmente, sono stati sintetizzati 20 dei 42 nuovi derivati 4-chinazolinonici, che sono stati saggiati preliminarmente sulla linea cellulare K562. Il derivato più attivo ha mostrato una IC50 di 18 µM. Sono in corso saggi enzimatici per valutare in vitro l’inibizione dell’enzima DHFR. Bibliografia 1 Al-Omary F.A.M.; et al, Bioorganic & Medicinal Chemistry, 2010, 18, 2849.

La Sortasi A è un enzima di membrana responsabile dell’ancoraggio delle proteine di superficie sulla parete cellulare dei batteri Gram-positivi. Essa è considerata un interessante obiettivo per lo sviluppo di nuovi farmaci anti-infettivi che mirino ad interferire con importanti meccanismi di virulenza Gram-positivi. In un precedente lavoro abbiamo indagato sull’attività antistafilococcica e antibiofilm di alcune Pirrolomicine naturali e sintetiche, composti pirrolici polialogenati attivi su patogeni Gram-positivi, alle concentrazioni di 1.5 e 0.045 µg/mL. I risultati biologici hanno mostrato percentuali di inibizione di biofilm comprese tra 50-80% [1]. Allo scopo di indagare sul loro meccanismo d’azione sono stati condotti studi di modellistica molecolare e saggi di inibizione in vitro sull’enzima Sortasi A (Figura 1). I risultati ottenuti indicano che la Sortasi A potrebbe essere il bersaglio sul quale le Pirrolomicine agiscono, con IC50 comprese tra 130-250 µM, nell’inibizione della formazione di biofilm. Bibliografia 1 Schillaci, D.; et al, Biofouling, 2010, 26, 433.

Tinnitus is a frequent symptom in audiological clinical practice characterized by an abnormal noise perceived in one or both ears or in the head, in which a patient has a conscious hearing percept in absence of external sound. Tinnitus might be caused by a homeostatic response of central dorsal cochlear nucleus auditory neurons that makes them hyperactive in compensation to auditory input loss. One hypothesis suggests that tinnitus is a sensory form of epilepsy that involves the cochlear nucleus and the inferior colliculus, which display impairment in the electrical activity in the auditory system. This alteration determines a synaptic plasticity in the dorsal cochlear nucleus that becomes a target for pharmacological compounds able to treat tinnitus. There is no effective drug treatment for tinnitus, but different studies propose the use of cannabinoid receptors agonist for their anti-epileptic activity, although their practical effects are still unclear. In this review, we want to analyze the emerging pharmacological approaches of cannabinoid receptor agonists to the therapy of tinnitus.

Background: Insomnia is the perception of inadequate, insufficient or non-restorative sleep. Of all sleep-related disorders, insomnia is the most common. It is important to remember that the sleep–wake cycle also plays a central role in the genesis of anxiety and depression. The aim of our study is to evaluate the association between sleep disturbances and anxiety and depression in a group of workers of both sexes who perform night shift work. Methods: Information on sleep disorders was collected by administering the Insomnia Severity Index (ISI) questionnaire. Statistical analysis was conducted using the Chi-square test to assess whether there were any differences between sex for those who were healthy or who were diagnosed with psychiatric disorders. Results: The results showed that there was a good percentage of subjects with insomnia problems, impairing normal daily activities and promoting the onset of fatigue, daytime sleepiness, cognitive performance deficits and mood disorders. Conclusion: We highlighted how anxious and depressive anxiety disorders are more pronounced in people who suffer from altered sleep–wake rhythms. Further research in this direction could prove to be fundamental for understanding the genesis of the onset of other disorders as well.

Almost two years after the beginning of the SARS-CoV-2 pandemic, the knowledge of which in the infectious and therapeutic spheres is constantly evolving, attention paid to the medicolegal aspects linked to this emergency phenomenon has mainly focused on the liability implications falling on healthcare personnel. With regard to the medicolegal assessment of the outcomes of COVID-19 illness, although it is a procedure that is commonly used, and although references in the assessment tables in force have been adhered to, a specific assessment protocol has not been standardized that takes into account, from an objective point of view, the degree of severity of the long-term residual outcomes and their impact on the social and working lives of subjects. This shortcoming appears to be attributable to the immediate need to categorize the results of COVID-19, but, in our opinion, it deserves an in-depth study and protocols to enable evaluation committees to draw up an assessment as precisely as possible and that is free of gaps, which could be the subject of legal disputes. The aim of the present work, in light of a worldwide problem, is to arrive at specific and univocal evaluation criteria for COVID-19 disease outcomes, applicable in different operational contexts of reemployment.

In the rat, prenatal exposure to diazepam (DZ) induces a permanent reduction in GABA/BZ receptor (R) function and behavioural abnormalities. Environmental modifications during early stages of life can influence brain development and induce neurobiological and behavioural changes throughout adulthood. Indeed, a subtle, periodic, postnatal manipulation increases GABA/BZ R activity and produces facilitatory effects on neuroendocrine and behavioural responses. We here investigated the impact of prenatal treatment with DZ on learning performance in adult 3- and 8-month-old male rats and the influence of a brief, periodic maternal separation on the effects exerted by prenatal DZ exposure. Learning performance was examined employing a non-aversive spatial, visual and/or tactile task, the "Can test". Behavioural reactivity, emotional state and fear/anxiety-driven behaviour were also examined using open field (OF), acoustic startle reflex (ASR) and elevated plus-maze (EPM) tests. A single daily injection of DZ (1.5 mg/kg, s.c.), over gestational days (GD) 14-20, induced, in an age-independent manner, a severe deficit in learning performance, a decrease in locomotor and explorative activity and an increase in peak amplitude in the ASR. Furthermore, anxiety-driven behaviour in EPM was disrupted. Daily maternal separation for 15 min over postnatal days 2-21 exerted opposite effects in all the paradigms examined. Prenatally DZ-exposed maternal separated rats, in contrast to respective non-separated rats, showed an improvement in learning performance, a decrease in emotionality and a normalization of the exploratory behaviour in EPM. These results suggest that a greater maternal care, induced by separation, can serve as a source for the developing brain to enhance neuronal plasticity and to prevent the behavioural abnormalities induced by prenatal DZ exposure. © 2005 Elsevier B.V. All rights reserved.

The sleep-wake cycle plays a fundamental role in maintaining the physiological balance of our body. Its alteration favours the genesis of several organic alterations and diseases including sleep disorders and the consumption of several substances of abuse. It has been reported that the work activity, especially that carried out during the night, is able to influence the sleep-wake cycle, promoting the development of insomnia, which, in turn, would subject the worker to a stressful condition such as to encourage adverse behaviour such as the use/abuse of psychotropic substances. Based on the above premises, the aim of our research was to evaluate, in night workers: (i) the pattern of consumption of alcoholic beverages; (ii) the presence of insomnia; and (iii) the possible correlation between alcohol consumption and insomnia disorder. We used the AUDIT-C test (the abbreviated version of the Alcohol Use Disorders Identification Test) and the Insomnia Severity Index to assess alcohol consumption and insomnia disorder, respectively. All questionnaires were completed by workers of both sexes belonging to different types of work activities, exclusively day or night. The results of our research show a higher propensity of night workers to consume alcoholic beverages than those who work during daytime hours, often in binge-drinking mode. In addition, an increase in the amount of alcohol consumed was found to be related to insomnia disorder, especially in night workers. This study provides further awareness of the importance of the negative impact of alcohol consumption on sleep quality in night workers.

Vertigo is not itself a disease, but rather a symptom of various syndromes and disorders that jeopardize balance function, which is essential for daily activities. It is an abnormal sensation of motion that usually occurs in the absence of motion, or when a motion is sensed inaccurately. Due to the complexity of the etiopathogenesis of vertigo, many pharmacological treatments have been tested for efficacy on vertigo. Among these drugs, cinnarizine, usually given together with dimenhydrinate, appears to be the first-line pharmacotherapy for the management of vertigo and inner ear disorders. Based on these considerations, the present non-interventional study aimed to investigate the clinical efficacy and tolerability of a fixed combination of cinnarizine (20 mg) and dimenhydrinate (40 mg) in patients suffering from vertigo-related symptoms. To this end, we enrolled 120 adults—70 males, and 50 females—with an average age of 64 years. Before beginning pharmacological treatment, all patients were screened for the intensity of vertigo, dizziness, and concomitant symptoms through the Visual Scale of Dizziness Disorders and Dizziness Handicap Inventory scales. At the end of the anamnestic evaluation, patients received the fixed-dose combination of cinnarizine (20 mg) plus dimenhydrinate (40 mg) 3 times daily, for 60 days. The results of this study provide further insight regarding the efficacy of the fixed combination when used to reduce symptoms of vestibular vertigo of central and/or peripheral origin, after both the 15- and 60-day therapies. Independent of the type of vertigo, the fixed combination was able to reduce dizziness- and vertigo-associated symptoms in more than 75% of all patients treated, starting from 15 days of therapy, and improving 60 days after starting the therapy. Interestingly, we also found differences between male and female patients in the framework of the pharmacological effects of therapy. This study provides further details concerning the therapeutic efficacy of the fixed combination of cinnarizine and dimenhydrinate, and also focuses attention on the possibility that these drugs could act in a gender-specific manner, paving the way for further research.