Ultraviolet photochemistry of 2-bromothiophene explored using universal ionization detection and multi-mass velocity-map imaging with a PImMS2 sensor.

The ultraviolet photochemistry of 2-bromothiophene (C4H3SBr) has been studied across the wavelength range 265-245 nm using a velocity-map imaging (VMI) apparatus recently modified for multi-mass imaging and vacuum ultraviolet (VUV, 118.2 nm) universal ionization. At all wavelengths, molecular products arising from the loss of atomic bromine were found to exhibit recoil velocities and anisotropies consistent with those reported elsewhere for the Br fragment [J. Chem. Phys. 142, 224303 (2015)]. Comparison between the momentum distributions of the Br and C4H3S fragments suggests that bromine is formed primarily in its ground (2P3/2) spin-orbit state. These distributions match well at high momentum, but relatively fewer slow moving molecular fragments were detected. This is explained by the observation of a second substantial ionic product, C3H3+. Analysis of ion images recorded simultaneously for several ion masses and the results of high-level ab initio calculations suggest that this fragment ion arises from dissociative ionization (by the VUV probe laser) of the most internally excited C4H3S fragments. This study provides an excellent benchmark for the recently modified VMI instrumentation and offers a powerful demonstration of the emerging field of multi-mass VMI using event-triggered, high frame-rate sensors, and universal ionization.

Cancer stem cells in laryngeal cancer: what we know.

Cancer stem cells (CSCs) are a group of cells with eternal life or infinite self-renewal ability, which have high migrating, infiltrative, and metastatic abilities. Though CSCs only account for a small proportion in tumors, the high resistance to traditional therapy exempts them from therapy killing and thus they can reconstruct tumors. Previous studies found that heterogeneity of cancer cells extensively exists in head and neck cancers. Our current knowledge, about CSCs in the laryngeal cancer (LC), largely depends on head and neck studies. Given the lack of systematic data about CSCs in LC, we propose a review of the literature, reporting the evidences of CSCs in tumorigenesis of LC, with the purpose to provide new insights into the prevention and/or treatment of laryngeal carcinoma.

Modifications to a commercially available linear mass spectrometer for mass-resolved microscopy with the pixel imaging mass spectrometry (PImMS) camera.

RATIONALE: Imaging mass spectrometry is a powerful analytical technique capable of accessing a large volume of spatially resolved, chemical data from two-dimensional samples. Probing the entire surface of a sample simultaneously requires a detector with high spatial and temporal resolutions, and the ability to observe events relating to different mass-to-charge ratios. METHODS: A commercially available time-of-flight mass spectrometer, designed for matrix-assisted laser desorption/ionization (MALDI) analysis, was combined with the novel pixel imaging mass spectrometry (PImMS) camera in order to perform multi-mass, microscope-mode imaging experiments. A number of minor modifications were made to the spectrometer hardware and ion optics so that spatial imaging was achieved for a number of small molecules. RESULTS: It was shown that a peak width of Δm50 % < 1 m/z unit across the range 200 ≤ m/z ≤ 800 can be obtained while also achieving an optimum spatial resolution of 25 µm. It was further shown that these data were obtained simultaneously for all analytes present without the need to scan the experimental parameters. CONCLUSIONS: This work demonstrates the capability of multi-mass, microscope-mode imaging to reduce the acquisition time of spatially distributed analytes such as multi-arrays or biological tissue sections. It also shows that such an instrument can be commissioned by effecting relatively minor modifications to a conventional commercial machine.

Otolaryngology adverse events following COVID-19 vaccines.

OBJECTIVE: Since the outbreak of COVID-19 pandemic, the international scientific community aimed at developing a vaccine to protect against the infection and prevent serious forms of the disease. To date, various adverse events of COVID-19 vaccines have been reported, mostly mild to moderate. MATERIALS AND METHODS: In this short communication, we reviewed available literature and described the most frequent otolaryngology adverse events reported after COVID-19 vaccination. RESULTS: The most frequent adverse events following COVID-19 vaccine described in the literature are represented by audiovestibular symptoms, such as tinnitus, sudden sensorineural hearing loss, vertigo, and dizziness. Other side effects include facial nerve palsy, epistaxis, and oral manifestations (lichen planus, bleeding, ulcers, and vesicles). CONCLUSIONS: COVID-19 vaccine is of utmost importance in limiting the spread of SARS-CoV-2. Otolaryngology-related side effects have been described, but none was severe or life threatening. The mechanisms underlying these effects are still mostly unknown.

Pharmacological drugs inducing ototoxicity, vestibular symptoms and tinnitus: a reasoned and updated guide.

The present work on drug-induced ototoxicity, tinnitus and vertigo represents the update and revision of a previous guide to adverse drug reactions for italian physicians (2005). The panorama of drug-induced side effects causing ototoxicity or symptoms such as tinnitus or dizziness and vertigo has enlarged in recent years, thanks to a better knowledge and a more specific attention of pharmaceutical firms and drug-control institutions. In daily clinical practice, there is a need for the family physician and the ENT specialist or audiologist (also in consideration of the possible medico-legal implications) to focus the attention on the possible risk of otological side effects. This would allow a clinical risk-benefit evaluation, weighing the possible clinical advantage in their field of competence against possible otological side-effects. The list of active ingredients and drugs is subdivided in categories based on their audiological and otoneurological side-effects, that have been signaled by the drug companies and/or ministerial notes. Drugs have also been subcategorized with regards to the field in which they are applied, the therapeutic indications and the clinical behaviour. They have also been organized in alphabetical order, for an easier consultation. The guide above, even if initially conceived for being used in Italy, also presents a more general and international interest, expecially as for as the concepts of pharmacology and the features of the active ingredients are concerned. The guide is, therefore, useful as for as we are concerned to any physician, regardless of the country he/she operates in.

Dietary Restriction for The Treatment of Meniere's Disease.

Meniere's disease (MD) is an idiopathic inner ear disorder characterized by spontaneous recurrent vertigo, fluctuating sensorineural hearing loss (SNHL), aural fullness and tinnitus. Endolymphatic hydrops (EH) of the inner ear is currently considered the pathophysiological mechanisms that underlies typical symptoms of MD. MD diagnosis is based on the criteria of the Baràny Society. There are many therapeutic options for MD, but none is considered effective by the scientific community. The first-line treatment commonly includes dietary modification, as low salt diet and reduction of alcohol and caffeine daily intake. Although some studies showed a positive effect of these dietary restrictions, even in the prevention of recurrences, currently there is no uniform consensus on their usefulness. New dietary approach, such SPC-flakes, are being evaluated: further assessments will be needed to validate their use in clinical practice.

Drugs inducing hearing loss, tinnitus, dizziness and vertigo: an updated guide.

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.

Correlation between otitis media with effusion and cranial deformation in children.

OBJECTIVE: Otitis media with effusion (OME), defined as the presence of fluid in the ear without signs of an acute infection, usually occurs after acute otitis media and could result in reduced sound transmission with hearing loss. Several risk factors have been suggested to be associated with OME, as well as the relationships between morphology anomalies of cranial bones and ear infections. The aim of this study is to investigate the correlation between OME and cranial deformation in a pediatric population. PATIENTS AND METHODS: Eighteen children (13 males and 5 females) with a diagnosis of unilateral OME based on otolaryngologic examination, conductive hearing loss and an asymmetric tympanogram type were enrolled in the study. Patients underwent osteopathic and physical examinations to evaluate the presence of cranial deformations. RESULTS: Our study showed a high percentage of skull asymmetry (94%) in the study sample; children were mainly dolichocephalic and with atypical swallowing (72%). Particularly, we observed an occipital flattening, mainly ipsilateral to the ear affected by OME. CONCLUSIONS: The results of the present study indicated that a high percentage of children with OME present a skull asymmetry with concomitant dolichocephaly, known to be associated with high arched palate which is also related to a higher incidence of OME.

Preliminary images from an adaptive imaging system.

I-ImaS (Intelligent Imaging Sensors) is a European project aiming to produce real-time adaptive X-ray imaging systems using Monolithic Active Pixel Sensors (MAPS) to create images with maximum diagnostic information within given dose constraints. Initial systems concentrate on mammography and cephalography. In our system, the exposure in each image region is optimised and the beam intensity is a function of tissue thickness and attenuation, and also of local physical and statistical parameters in the image. Using a linear array of detectors, the system will perform on-line analysis of the image during the scan, followed by optimisation of the X-ray intensity to obtain the maximum diagnostic information from the region of interest while minimising exposure of diagnostically less important regions. This paper presents preliminary images obtained with a small area CMOS detector developed for this application. Wedge systems were used to modulate the beam intensity during breast and dental imaging using suitable X-ray spectra. The sensitive imaging area of the sensor is 512 x 32 pixels 32 x 32 microm(2) in size. The sensors' X-ray sensitivity was increased by coupling to a structured CsI(Tl) scintillator. In order to develop the I-ImaS prototype, the on-line data analysis and data acquisition control are based on custom-developed electronics using multiple FPGAs. Images of both breast tissues and jaw samples were acquired and different exposure optimisation algorithms applied. Results are very promising since the average dose has been reduced to around 60% of the dose delivered by conventional imaging systems without decrease in the visibility of details.

Empirical electro-optical and x-ray performance evaluation of CMOS active pixels sensor for low dose, high resolution x-ray medical imaging.

Monolithic complementary metal oxide semiconductor (CMOS) active pixel sensors with high performance have gained attention in the last few years in many scientific and space applications. In order to evaluate the increasing capabilities of this technology, in particular where low dose high resolution x-ray medical imaging is required, critical electro-optical and physical x-ray performance evaluation was determined. The electro-optical performance includes read noise, full well capacity, interacting quantum efficiency, and pixels cross talk. The x-ray performance, including x-ray sensitivity, modulation transfer function, noise power spectrum, and detection quantum efficiency, has been evaluated in the mammographic energy range. The sensor is a 525 x 525 standard three transistor CMOS active pixel sensor array with more than 75% fill factor and 25 x 25 microm pixel pitch. Reading at 10 f/s, it is found that the sensor has 114 electrons total additive noise, 10(5) electrons full well capacity with shot noise limited operation, and 34% interacting quantum efficiency at 530 nm. Two different structured CsI:Tl phosphors with thickness 95 and 115 microm, respectively, have been optically coupled via a fiber optic plate to the array resulting in two different system configurations. The sensitivity of the two different system configurations was 43 and 47 electrons per x-ray incident on the sensor. The MTF at 10% of the two different system configurations was 9.5 and 9 cycles/mm with detective quantum efficiency of 0.45 and 0.48, respectively, close to zero frequency at approximately 0.44 microC/kg (1.72 mR) detector entrance exposure. The detector was quantum limited at low spatial frequencies and its performance was comparable with high resolution a: Si and charge coupled device based x-ray imagers. The detector also demonstrates almost an order of magnitude lower noise than active matrix flat panel imagers. The results suggest that CMOS active pixel sensors when coupled to structured CsI:Tl can be used for conventional and advanced digital mammography due to their low noise, high resolution performance.

Acquired sensorineural hearing loss in children: current research and therapeutic perspectives.

The knowledge of mechanisms responsible for acquired sensorineural hearing loss in children, such as viral and bacterial infections, noise exposure, aminoglycoside and cisplatin ototoxicity, is increasing and progressively changing the clinical management of affected patients. Viral infections are by far the most relevant cause of acquired hearing loss, followed by aminoglycoside and platinum derivative ototoxicity; moreover, cochlear damage induced by noise overexposure, mainly in adolescents, is an emerging topic. Pharmacological approaches are still challenging to develop a truly effective cochlear protection; however, the use of steroids, antioxidants, antiviral drugs and other small molecules is encouraging for clinical practice. Most of evidence on the effectiveness of antioxidants is still limited to experimental models, while the use of corticosteroids and antiviral drugs has a wide correspondence in literature but with controversial safety. Future therapeutic perspectives include innovative strategies to transport drugs into the cochlea, such as molecules incorporated in nanoparticles that can be delivered to a specific target. Innovative approaches also include the gene therapy designed to compensate for abnormal genes or to make proteins by introducing genetic material into cells; finally, regenerative medicine (including stem cell approaches) may play a central role in the upcoming years in hearing preservation and restoration even if its role in the inner ear is still debated.

When alarm bells ring: emergency tinnitus.

OBJECTIVE: The aim of this study is to develop a diagnostic-therapeutic algorithm for those suffering from tinnitus who seek emergency aid. MATERIALS AND METHODS: A literature review has been performed on articles from the last 30 years. RESULTS: It is important to activate medical or surgical diagnostic and therapeutic strategies, in order to safeguard and rehabilitate the various functions affected. Psychiatric comorbidity is the most frequent pathological condition of those with serious or catastrophic tinnitus. In these cases, mortality risk is linked to suicide, morbidity to tinnitus-correlated distress. CONCLUSIONS: Tinnitus, mainly linked to loss of hearing, is a frequent symptom among the population at large. About 7% of those affected by tinnitus turn to their doctor to solve their problem, while between 0.5 and 2% request urgent medical assistance. Their cry for help may be the result of an acute onset of tinnitus or the rapid impairment of an already chronic condition. Tinnitus is not considered an urgent ear, nose and throat (ENT) condition by the Associazione Otorinolaringologi Ospedalieri Italiani (AOOI) [Italian Association of Hospital ENT], even though there are many pathological conditions, sometimes serious, associated with tinnitus and emergency action is necessary to reduce the risk of morbidity and mortality.

[An updated guide on drugs inducing ototoxicity, tinnitus and vertigo]. / Guida ed aggiornamento sui farmaci ototossici, tinnitogeni e vertigogeni.

The argument of the iatrogenic side effects of pharmacological origin that can cause ototoxic effects or only disacustic symptoms like the tinnitus, without consequent degenerative effects, is enlarged in these last years. It is because of the great knowledge based on the careful attention from the pharmaceutical institutions which are responsible for the control of medicines and drugs. In the medical practice and in that specialty field born the need to gather, also in consideration of the possible medico-legal implications, those elements which will suppose the risk of otologic side effects. This will allow the physicians to evaluate the possible clinical advantage of a treatment, in their own field of competence, balancing them with their possible side effects in the otologic field. For this purpose, we have elaborated some updated lists of drugs with possible side effects of ototoxicity, tinnitus and vertigo; furthermore, we considered these drugs as could theoretically have influence on the auditory neurochemical progressing since they have excitatory or inhibitory action on the neurotransmitters and their receptors, but not signaled by the sources of institutional information.

Comparative efficacy of cefotetan and clindamycin plus amikacin as antimicrobial prophylaxis for major head and neck surgery.

A total of 41 patients were randomly allocated to receive either cefotetan (total dose, 20 g) or clindamycin (total dose, 12 g) plus amikacin (total dose, 5 g) as perioperative antimicrobial prophylaxis for major head and neck surgery. The two groups were similar in age, male to female ratio, stage of cancer, and the various types of surgery. No patient received radiotherapy or chemotherapy before surgery. The wound infection rate was 4% in the group of patients receiving cefotetan and 0% in the group receiving clindamycin plus amikacin. No major side effects were observed in either group. On the basis of this study a five-day perioperative course with cefotetan may be considered effective antimicrobial prophylaxis in patients undergoing major head and neck oncologic surgery.

[Comments on organization and activity of ENT day hospital department: three years of experience]. / Riflessioni su ...organizzazione ed attività di un reparto di day hospital in O.R.L.: esperienza di un triennio.

The authors deal with organizational and technical aspects concerning otorhinolaryngological day hospital's management. They explain purposes and reasons leading to the establishment of this sort of service; they analyse related problems and the adopted methodologies for simplifying admission procedures. They report a statistical survey regarding the period from May 1991 to May 1994, concerning surgical and medical operations, and instrumental diagnostic researches performed at the IV ENT Department of "La Sapienza" University of Rome. The statistical analysis concerning the 1526 patients sent to this department, shows the downright prevalence of surgical operations performed in operating room (52%). Ambulatory operations and instrumental diagnostic researches account respectively for 39.6% and for 29.3% of all hospitalizations. Among all surgery operations performed in operating room stand out the notice incidence of therapeutical and diagnostic microlaryngoscopies. The most frequent ambulatory operations were the removal of tracheal cannula (21%), while TC was the most frequent of all instrumental diagnostic researches. A careful selection of patients, on the basis of their general condiction, account for the low incidence of subjects not discharged within 24 hours. After having analyzed the survey's data, the authors underline advantages and finalities of day hospital: a shorter hospital stay, reduction of hospitalization's costs, and a larger related number of patients to be contented. Finally they hope that this sort of service will spread more.

Recurrent respiratory papillomatosis by HPV: review of the literature and update on the use of cidofovir.

Recurrent respiratory papillomatosis is a viral induced disease characterised by exophytic epithelial lesions affecting the larynx. The problem with its treatment is the high recurrence of papilloma growth after surgical removal. The aim of our review is to analyse the actual use of cidofovir, an agent used in adjuvant therapy. We have reviewed 6 manuscripts that included a total of 118 patients. The parameters taken into account were: concentration of infiltrated cidofovir (mg/ml), therapeutic response, relapse-free time (months), side effects, genotypes (HPV-6/11/18) and evolution of dysplasia. Cidofovir was injected at concentrations from 2.5 to 15 mg/ml, therapeutic response was from 56.25% to 82.3% and relapse-free time was from 10.05 to 49 months. There were 2 cases of dysplasia during therapy. Ten patients had been infected by HPV-6, 4 patients by HPV-11 and 10 patients by HPV-6 and HPV-11. The purposes of our review include the following: to stress that the juvenile form is more aggressive than other forms, to demonstrate than the drug has good adjuvant action although it does not significantly change the final response to the disease, to show that side effects are modest and, finally, to disprove the hypothesis that cidofovir may promote evolution towards dysplasia. In conclusion, combination of surgical removal and injection of cidofovir is associated with good response in recurrent respiratory papillomatosis.

Deafness in Italy: an epidemiological and socio-demographic study.

OBJECTIVES: Hearing loss is very common in our society, but epidemiological data on deafness in Italy is lacking. A.I.R.S. onlus (Italian Association for Research on Deafness) yearly launches the National Day for the Fight Against Deafness (NDFAD). During this events, that are held every year, it is possible to perform a free hearing test in all the facilities that have joined the initiative throughout Italy (240 hospitals joined in 2011). AIM: to report data collected throughout the "A.I.R.S. National Day for the Fight against Deafness" of the last years, focusing in particular but not only on audiometric outcomes. METHODS: demographic and social data, as well as audiometric outcomes, was collected on forms that have been subsequently stored in a on-line database and analyzed with MySQL and Microsoft Excel. CONCLUSIONS: This data are important in order to describe the "hearing health" of the Italian population, and is a first step towards creating a database with epidemiological and preventive aims, a strongly felt need both at national and at regional level.

Cogan's syndrome: an autoimmune inner ear disease.

OBJECTIVES: The objective of our study was to review our current knowledge of the aetiopathogenesis of Cogan's syndrome, including viral infection and autoimmunity, and to discuss disease pathogenesis with relevance to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY: Relevant publications on the aetiopathogenesis and pharmacotherapy of Cogan's syndrome from 1945 to 2012 were analysed. RESULTS AND CONCLUSIONS: Cogan's syndrome is a rare autoimmune vasculitis, and its pathogenesis is unknown. Infection, but primarily autoimmunity, may play contributing roles in the pathogenesis of this disease. It is characterised by ocular and audiovestibular symptoms similar to those of Meniere's syndrome. Approximately 70% of patients have systemic disease, of which vasculitis is considered the pathological mechanism. The immunologic theory is based on the release of auto-antibodies against corneal, inner ear and endothelial antigens, and of anti-nuclear cytoplasmic auto-antibodies (ANCA). Corticosteroids are the first line of treatment, and multiple immunosuppressive drugs have been tried with varying degrees of success. Tumour necrosis factor (TNF)-alpha blockers are a category of immunosuppressive agents representing a recent novel therapeutic option in Cogan's syndrome.

Vogt-Koyanagi-Harada syndrome.

OBJECTIVES: The objectives of this study are to review our current knowledge of the aetiopathogenesis of Vogt-Koyanagi-Harada syndrome, including viral infection, genetic factors and immunomediated mechanisms, and to discuss pathogenesis and its relevance to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY: Relevant publications from 1965 to 2012 on the aetiopathogenesis and pharmacotherapy of VKHS were analysed. RESULTS AND CONCLUSION: Vogt-Koyanagi-Harada syndrome (VKHS) is a rare multisystemic autoimmune disease that affects tissues containing melanin, including the eye, inner ear, meninges, and skin. The disease is characterised by bilateral uveitis associated with a varying constellation of auditory, neurological and cutaneous manifestations. The disease occurs more frequently among people with darker skin pigmentation. Asians, Native Americans, and Hispanics are most frequently affected. It predominates in patients aged between 20 and 50years, and females are affected more frequently, with a female:male ratio of 2:1. The classic clinical course is characterised by bilateral panuveitis, hypoacusis, and meningitis, in addition to cutaneous involvement with poliosis, vitiligo, and alopecia. Although the exact cause of VKH disease remains unknown, it is thought to be a T-cell-mediated autoimmune process directed against melanocytes. VKHS classically begins with vague systemic symptoms suggestive of a viral infection, although a clear association between a specific viral agent and the disease has not been established. Genetic factors may play an important role in the loss of self-tolerance in VKHS. The HLA-DRB1*0405 allele is the main susceptibility allele for VKHS. Early and aggressive systemic corticosteroids are still the primary initial therapy for VKHS. Ocular complications may require an intravitreous injection of corticosteroids. Despite proper treatment with steroids, a number of patients experience recurrent attacks or steroid-associated complications. Thus, non steroid immunomodulatory therapy (IMT) has become necessary for the treatment of VKHS.

The application of the fast, multi-hit, pixel imaging mass spectrometry sensor to spatial imaging mass spectrometry.

Imaging mass spectrometry is a powerful technique that allows chemical information to be correlated to a spatial coordinate on a sample. By using stigmatic ion microscopy, in conjunction with fast cameras, multiple ion masses can be imaged within a single experimental cycle. This means that fewer laser shots and acquisition cycles are required to obtain a full data set, and samples suffer less degradation as overall collection time is reduced. We present the first spatial imaging mass spectrometry results obtained with a new time-stamping detector, named the pixel imaging mass spectrometry (PImMS) sensor. The sensor is capable of storing multiple time stamps in each pixel for each time-of-flight cycle, which gives it multi-mass imaging capabilities within each pixel. A standard velocity-map ion imaging apparatus was modified to allow for microscope mode spatial imaging of a large sample area (approximately 5 × 5 mm(2)). A variety of samples were imaged using PImMS and a conventional camera to determine the specifications and possible applications of the spectrometer and the PImMS camera.