Search

STUDY OBJECTIVES: Different therapeutic strategies have been investigated for the treatment of positional obstructive sleep apnea, but more evidence is needed about efficacy and compliance. The objective of this study was to describe the efficacy of vibrotactile neck-based treatment in patients with positional obstructive sleep apnea with different degrees of obstructive sleep apnea severity who were followed for 6 months. METHODS: This is a retrospective study including 162 patients with positional obstructive sleep apnea undergoing vibrotactile neck-based positional therapy. We compared polysomnographic data obtained at baseline and during positional therapy after 1 month. We performed a subgroup analysis based on obstructive sleep apnea severity. Furthermore, we analyzed follow-up data in 84/162 (51.8%) patients with particular focus on discontinuation and complications related to the device. RESULTS: We observed a significant difference between mean baseline obstructive apnea-hypopnea index (OAHI; 21.9 ± 9.9 events/h) and during positional therapy (12 ± 9.2 events/h; P < .01). Moreover, 87/162 (54.9%) patients showed a reduced baseline OAHI of at least 50% and 38/162 (23.4%) achieved complete disease control (OAHI < 5 events/h). At subgroup analysis, at least 50% reduction from baseline OAHI was observed in 56.8% of patients with mild, 55% with moderate, and 47.4% with severe OAHI, whereas complete control of disease was achieved in 50% of patients with mild, 22.5% with moderate, and 7.9% with severe OAHI. At a 6-month follow-up, only 35/84 patients (41.6%) were regularly using the device, with a mean of 5.9 ± 1.2 days per week. CONCLUSIONS: Our results on the efficacy and long-term adherence to vibrotactile neck-based positional therapy showed that positional therapy can be an efficient first-line treatment option for mild positional obstructive sleep apnea and in selected cases of moderate disease. Long-term compliance is limited because of complications and low satisfaction in some patients. CITATION: De Corso E, Mastrapasqua RF, Fiorita A, et al. Efficacy and long-term follow-up of positional therapy by vibrotactile neck-based device in the management of positional OSA. J Clin Sleep Med. 2020;16(10):1711–1719.

Background: The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) represents a major threat to human health, which impairs the functionality of several organs. One of the hardest challenges in the fight against COVID-19 is the development of wide-scale, effective, and rapid laboratory tests to control disease severity, progression, and possible sudden worsening. Monitoring patients in real-time is indeed highly demanded in this pandemic era when physicians need reliable and quantitative tools to prioritize patients’ access to intensive care departments. In this regard, salivary biomarkers are extremely promising, as they allow for a fast and non-invasive specimens’ collection, which can be repeated multiple times. Methods: We compare salivary levels of immunoglobulin A subclasses (IgA1 and IgA2) and free-light chains (FLC k and λ) in a cohort of 29 SARS-CoV-2 patients and 21 healthy subjects. Results: We found that each biomarkers differs significantly between the two groups, with p-values ranging from 10-8 to 10-4. The performance ranking of these markers, shows that λFLC level (p=1.4e-8) is the best-suited candidate to discriminate the two groups, with an accuracy of 0.94 (0.87-1.00 95% CI), a precision of 0.91 (0.81-1.00 95% CI), a sensitivity of 1.00 (0.96-1.00 95% CI) and a specificity of 0.86 (0.70-1.00 95% CI). Conclusion: These results suggest λFLC as an ideal indicator of patient conditions. This is more strengthened in consideration that λFLC half-life (approximately 6 hours) is significantly shorter than the IgA one (21 days): thus λFLC appears displaying the potential to effectively monitor patients fluctuation in real-time.

Central sleep apnoea (CSA) is a lack of drive to breathe during sleep, which can occur in physiologic as well as in pathologic conditions. A particular type of CSA, defined treatment-emergent CSA (TECSA), may occur after the treatment of obstructive sleep apnoea syndrome (OSAS), either with CPAP or surgery. TECSA is transitory and seems to be related to the severity of OSAS. We describe a 51-year-old man affected by severe OSAS who developed severe, transient CSA immediately after upper airways surgery. We believe that CSA was triggered by the sudden variation in nocturnal arterial PCOApnee notturne centrali post chirurgia disostruttiva delle prime vie aeree nei pazienti affetti da OSAS.L’Apnea Centrale nel Sonno (CSA) è caratterizzata da un mancato input a compiere l’atto respiratorio durante il sonno e può verificarsi sia in condizioni fisiologiche che in condizioni patologiche. Un particolare tipo di CSA, definito come “Apnea Centrale nel Sonno Emergente dal Trattamento” (TECSA), può verificarsi dopo il trattamento della Sindrome delle Apnee Ostruttive durante il Sonno (OSAS), sia dopo ventiloterapia con CPAP che dopo intervento chirurgico. La TECSA è di solito transitoria e sembra correlata alla gravità dell’OSAS. Descriviamo un uomo di 51 anni affetto da OSAS grave, che ha sviluppato gravi e transitorie apnee centrali nel sonno, immediatamente dopo l’intervento chirurgico delle vie aeree superiori. Ipotizziamo che la CSA sia stata innescata dalla brusca variazione dei valori notturni di PCO

The ongoing outbreak of coronavirus disease 2019 (COVID-19), which impairs the functionality of several organs, represents a major threat to human health. One of the hardest challenges in the fight against COVID-19 is the development of wide-scale, effective, and rapid laboratory tests to control disease severity, progression, and possible sudden worsening. Monitoring patients in real-time is highly demanded in this pandemic era when physicians need reliable and quantitative tools to prioritize patients’ access to intensive care departments. In this regard, salivary biomarkers are extremely promising, as they allow for the fast and non-invasive collection of specimens and can be repeated multiple times. Methods: We compare salivary levels of immunoglobulin A subclasses (IgA1 and IgA2) and free light chains (kFLC and λFLC) in a cohort of 29 SARS-CoV-2 patients and 21 healthy subjects. Results: We found that each biomarker differs significantly between the two groups, with p-values ranging from 10−8 to 10−4. A Receiving Operator Curve analysis shows that λFLC level is the best-suited candidate to discriminate the two groups (AUC = 0.96), with an accuracy of 0.94 (0.87–1.00 95% CI), a precision of 0.91 (0.81–1.00 95% CI), a sensitivity of 1.00 (0.96–1.00 95% CI), and a specificity of 0.86 (0.70–1.00 95% CI). Conclusion: These results suggest λFLC as an ideal indicator of patient conditions. This hypothesis is strengthened by the consideration that the λFLC half-life (approximately 6 h) is significantly shorter than the IgA one (21 days), thus confirming the potential of λFLC for effectively monitoring patients’ fluctuation in real-time.

Il trattamento con dispositivi di avanzamento mandibolare (MAD) rappresenta un’efficace alternativa terapeutica per i pazienti affetti da roncopatia semplice, OSAS di grado lieve/moderato e in casi selezionati di OSAS grave con scarsa tollerabilità alla terapia ventilatoria con C-PAP. Pertanto è importante identificare dei criteri oggettivi per selezionare i pazienti che possono beneficiare del trattamento con i sistemi di avanzamento mandibolare (MAD). In letteratura sono stati descritti vari fattori predittivi sia antropometrici che polisonnografici, mentre esistono ancora controversie circa il ruolo della Sleep Endoscopy e della manovra di avanzamento mandibolare bimanuale durante lo stesso esame come fattori predittivi del successo terapeutico con MAD. In questo studio descriviamo la nostra esperienza nel management di pazienti affetti da OSAS lieve/moderata trattati con MAD e selezionati mediante “sleep endoscopy”. Abbiamo eseguito una valutazione prospettica longitudinale di una serie consecutiva di pazienti giunti alla nostra osservazione con diagnosi di OSAS lieve/moderata e sottoposti a sleependoscopy. Durante il sonno indotto farmacologicamente è stata eseguita una delicata manovra di avanzamento mandibolare con escursione inferiore ai 5 mm e abbiamo riscontrato che in 30 dei 65 pazienti (46,2%) lo spazio respiratorio non migliorava in modo significativo a livello dei siti di ostruzione osservati, mentre in 35 dei 65 pazienti (53,8%) si osservava un miglioramento significativo tale da poter indicare terapia con MAD. In 7 dei 35 pazienti venivano riscontrate condizioni che ostacolavano l’applicazione del MAD per cui 28 dei 35 pazienti sono stati sottoposti a terapia con MAD. Dopo 3 mesi di trattamento abbiamo documentato un miglioramento significativo dell’indice di Epworth medio [(7,35 ± 2,8 vs 4,1 ± 2,2 (p < 0.05)], dell’AHI medio [(21.4 ± 6 eventi per ora verso 8,85 ± 6,9 (p < 0.05) ] e dell’ODI medio [(18.6 ± 8 eventi per ora versus 7 ± 5.8 (p < 0.05)]. Abbiamo inoltre osservato che l’AHI migliorava di almeno il 50% rispetto al basale nel 71.4% dei pazienti selezionati mediante sleep endoscopy. In questo studio, la terapia con i dispositivi di avanzamento mandibolare è stata prescritta con successo sulla base non soltanto dell’indice di apnea/ipopnea, ma anche dei reperti della sleep endoscopy e della manovra di avanzamento mandibolare, ottenendo una visione diretta degli effetti della protrusione mandibolare sullo spazio respiratorio in corrispondenza dei siti di ostruzione, e ottenendo una buona ottimizzazione della selezione dei pazienti per il trattamento con MAD.

Drug-induced sleep endoscopy (DISE) is an important procedure in diagnostic pathway of patients affected by moderate OSAS. However, the Italian National Health System does not provide any compatible Diagnosis-related-group (DRG) code codification for DISE, which makes it impossible to obtain regional reimbursement. In order to overcome this problem, DISE is usually associated with other codified surgical procedures. The aim of our study is to assess the association of turbinate decongestion (TD) and DISE in order to combine in a single operating session diagnostic and therapeutic procedures. The objective of our work is to assess the role of nasal surgery on symptoms of moderate OSA. Recent studies have confirmed that isolated nasal surgery improves quality of life (QOL), but not the apnoea hypopnoea index (AHI) during polygraph registration. We enrolled 30 patients, aged between 29 and 64 years (mean 50.53 ± 9.20), 26 males and 4 females, with a mean BMI of 26.07 ± 2.81 kg/mOSAS di grado moderato e decongestione dei turbinati: efficacia chirurgica nel migliorare la qualità di vita e la compliance della CPAP utilizzando l’Epworth score e lo SNOT-20 score.La DISE (Drug Induced Sleep Endoscopy) è una procedura importante nella gestione diagnostica dei pazienti affetti da OSAS moderata. Il Sistema Sanitario Nazionale, tuttavia, non riconosce alcun DRG per tale metodica e ciò non consente di ottenere il rimborso regionale. Per superare questo problema di gestione di spesa sanitaria, di solito si associa la DISE a un’altra procedura chirurgica codificata. L’obiettivo del nostro studio è definire se l’associazione della decongestione dei turbinati alla DISE possa garantire un risultato terapeutico in aggiunta alla procedura diagnostica e migliorare la sintomatologia dei pazienti affetti da OSAS moderata. Recenti studi confermano che la sola chirurgia nasale migliora la qualità di vita ma non l’AHI (Indice Apnea-Ipopnea) durante la polisonnografia. Abbiamo arruolato 30 pazienti di età compresa tra 29 e 64 anni (media 50,53 ± 9,20), 26 maschi e 4 femmine con un BMI medio di 26,07 ± 2,81 kg/m

Saliva testing is a non-invasive and inexpensive test that can serve as a source of information useful for diagnosis of disease. As we enter the era of genomic technologies and -omic research, collection of saliva has increased. Recent proteomic platforms have analysed the human salivary proteome and characterised about 3000 differentially expressed proteins and peptides: in saliva, more than 90% of proteins in weight are derived from the secretion of three couples of "major" glands; all the other components are derived from minor glands, gingival crevicular fluid, mucosal exudates and oral microflora. The most common aim of proteomic analysis is to discriminate between physiological and pathological conditions. A proteomic protocol to analyze the whole saliva proteome is not currently available. It is possible distinguish two type of proteomic platforms: top-down proteomics investigates intact naturally-occurring structure of a protein under examination; bottom-up proteomics analyses peptide fragments after pre-digestion (typically with trypsin). Because of this heterogeneity, many different biomarkers may be proposed for the same pathology. The salivary proteome has been characterised in several diseases: oral squamous cell carcinoma and oral leukoplakia, chronic graft-versus-host disease Sjögren's syndrome and other autoimmune disorders such as SAPHO, schizophrenia and bipolar disorder, and genetic diseases like Down's Syndrome and Wilson disease. The results of research reported herein suggest that in the near future human saliva will be a relevant diagnostic fluid for clinical diagnosis and prognosis.Lo studio della proteomica salivare, test economico e non invasivo, rappresenta una fonte di numerose informazioni, ed è utile per la diagnosi di svariate malattie. Da quando siamo entrati nell’era della tecnologia genomica e delle scienze “omiche”, la raccolta di campioni salivari è aumentata esponenzialmente. Recenti piattaforme proteomiche hanno analizzato il proteoma salivare umano, caratterizzando circa 3000 peptidi e proteine, espressi in maniera differente: più del 90% in peso deriva dalla secrezione delle tre ghiandole salivari maggiori, mentre la restante parte proviene dalle ghiandole salivari minori, dal fluido crevicolare gengivale, da essudati mucosi e dalla microflora orale. L’obiettivo principale dell’analisi proteomica è discriminare tra condizioni fisiologiche e patologiche. Ad oggi, tuttavia, non esiste un preciso protocollo che permetta di analizzare l’intero proteoma salivare, pertanto sono state realizzate svariate strategie. Innanzitutto, è possibile distinguere due tipologie di piattaforme proteomiche: l’approccio “top-down” prevede l’analisi delle proteine sotto esame come entità intatte; nell’approccio “bottom-up” la caratterizzazione della proteina avviene mediante lo studio dei peptidi ottenuti dopo digestione enzimatica (con tripsina tipicamente). A causa di questa eterogeneità, per una stessa patologia sono stati proposti differenti biomarkers. Il proteoma salivare è stato caratterizzato in numerose malattie: carcinoma squamoso e leucoplachie orali, malattia del trapianto contro l’ospite (GVHD) cronica, sindrome di Sjögren e altri disordini autoimmuni come la sindrome SAPHO (sinovite, acne, pustolosi, iperostosi e osteite), schizofrenia e disordine bipolare, malattie genetiche come la sindrome di Down o la malattia di Wilson. In conclusione, i risultati delle ricerche riportate in questa review suggeriscono che nel prossimo futuro la saliva diverrà un fluido di indubbia rilevanza diagnostica utile per fini clinici, sia diagnostici, sia prognostici.

The aim of the present study is to establish if the vestibular evoked myogenic potentials (VEMPs) could be used as a clinical test for the evaluation of vestibular function in children affected by myelomeningocele (MMC). Fifteen children, aged between 3 and 17 years, who had been affected by MMC were investigated. Data obtained from these children were compared with normal data from healthy children of the same age. Electromyographic activity of sternocleidomastoid muscle was recorded, while children were laid supine and asked to raise their head off the bed in order to activate their neck flexors bilaterally. The saccular receptors were acoustically stimulated with a logon of 500 Hz at an intensity of 130 dB peSPL presented monaurally through earphones. In each recording, we analyzed latencies and amplitudes of the p13-and n23 waves and the amplitude ratio between the two ears. VEMPs were detected to be normal in 13 patients. In particular, the mean p13 and mean n23 latencies were 15.7 (±1.4) and 21.7 (±1.1) ms, respectively; the mean amplitude value was 84.7 (±36.6), while the mean amplitude ratio was 17.4 (±12). A comparison of latencies and amplitude ratios between the children and healthy control group did not reveal any significant difference. On the contrary, a comparison of amplitude values between the two groups showed significant differences. In conclusion, vestibulocollic reflex is normal in patients affected by MMC, and VEMPs could represent a valid and noninvasive technique eligible to investigate the vestibular functions in these children.

An HPLC-ESI-MS analysis of adult human whole saliva evidenced three protein masses (M average 11,487 +/- 2, 11,301 +/- 2 and 22,362 +/- 3 Da) eluting in the 32.5-35.0 mwin range. Treatment in reducing conditions allowed establishing that they are S-derivatives of N-terminal acetylated cystatin B, namely its S-glutathionyl, S-cysteinyl and S-S dimer. The identification was confirmed by high resolution HPLC-ESI-MS-MS experiments on the intact naturally occurring proteins and their tryptic digests. S-unmodified cystatin B is rarely detectable in whole saliva of healthy adults (5 subjects out of 65) and its percentage does not overcome approximately 20% of total cystatin B (11 +/- 9%). In the majority of subjects (60 out of 65) the mean percentages of the S-modified derivatives were S-glutathionyl 53 +/- 13%, S-cysteinyl 15 +/- 5%, S-S 2-mer 32 +/- 13%. Variations of the percentages of these S-modified derivatives of cystatin B could be indicative of oral oxidative stress. As we are aware, this is the first time that S-glutathionylation and S-cysteinylation were described as extensive PTM of a salivary protein and the first time that these PTMs were detected in naturally occurring cystatin B. (C) 2011 Elsevier B.V. All rights reserved.

This study describes the identification and structural characterization of Sus scrofa statherin. HPLC–electrospray ionization mass spectrometry analysis on pig parotid secretory granule extracts evidenced a peptide with a molecular mass value of 5381.1 ± 0.6 Da and its truncated form, devoid of the C-terminal Ala residue, with a molecular mass value of 5310.1 ± 0.6 Da. The complete sequence of pig statherin gene was determined by sequencing the full-length cDNA obtained by rapid amplification of cDNA ends. The gene is 549 base pairs long and contains an open reading frame of 185 nucleotides, encoding a 42-amino acid secretory polypeptide with a signal peptide of 19 residues. This sequence presents some typical features of the four statherins characterized till now, showing the highest degree of amino acid identity with bovine (57%) and human statherin (39%). Pig statherin is mono-phoshorylated on Ser-3, while primate statherins already characterized are di-phosphorylated on Ser-2 and Ser-3. This difference, probably connected to the Asp-4 Glu substitution, suggests the involvement of the Golgi-casein kinase, which strictly recognizes the SX(E/pS) consensus sequence. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.

To elucidate the localization of post-translational modifications of different classes of human salivary proteins and peptides (acidic and basic proline-rich proteins (PRPs), Histatins, Statherin, P-B peptide, and "S type" Cystatins) a comparative reversed phase HPLC-ESI-MS analysis on intact proteins of enriched granule preparations from parotid and submandibular glands as well as parotid, submandibular/sublingual (Sm/Sl), and whole saliva was performed. The main results of this study indicate the following. (i) Phosphorylation of all salivary peptides, sulfation of Histatin 1, proteolytic cleavages of acidic and precursor basic PRPs occur before granule storage. (ii) In agreement with previous studies, basic PRPs are secreted by the parotid gland only, whereas all isoforms of acidic PRPs (aPRPs) are secreted by both parotid and Sm/Sl glands. (iii) Phosphorylation levels of aPRPs, Histatin 1, and Statherin are higher in the parotid gland, whereas the extent of cleavage of aPRP is higher in Sm/Sl glands. (iv) O-Sulfation of tyrosines of Histatin 1 is a post-translational modification specific for the submandibular gland. (v) The concentration of Histatin 3, Histatin 5, and Histatin 6, but not Histatin 1, is higher in parotid saliva. (vi) Histatin 3 is submitted to the first proteolytic cleavage (generating Histatins 6 and 5) during granule maturation, and it occurs to the same relative extent in both glands. (vii) The proteolytic cleavages of Histatin 5 and 6, generating a cascade of Histatin 3 fragments, take place after granule secretion and are more extensive in parotid secretion. (viii) Basic PRPs are cleaved in the oral cavity by unknown peptidases, generating various small proline-rich peptides. (ix) C-terminal removal from Statherin is more extensive in parotid saliva. (x) P-B peptide is secreted by both glands, and its relative quantity is higher in submandibular/sublingual secretion. (xi) In agreement with previous studies, S type Cystatins are mainly the product of Sm/Sl glands.

Basic proline-rich proteins (bPRPs) are a class of proteins widely present in saliva of humans and other mammals. They are synthesized as preproproteins and enzymatically cleaved into small peptides before secretion from the salivary glands. Recently, we characterized two proline-rich peptides (SP-A and SP-B) in parotid secretory granules of pig (Sus Scrofa) that are derived from three isoforms of a PRP proprotein (Swiss-Prot data bank: Q95JC9-1, Q95JC9-2 and Q95JC9-3). Together the coding regions for SP-A and SP-B, which are repeated many times, account for 52-70% of the coding regions of the PRP proproteins. This study was undertaken to identify peptides encoded by unassigned regions of the PRP proproteins. RP-HPLC-ESI-IT-MS analysis of enriched granule preparations from pig parotid glands by two different analytical strategies identified ten new proline-rich peptides derived from the three proproteins. Together with the coding regions for SP-A and SP-B already identified it was possible to assign 68-75% of the proproteins coding regions. The peptide sequences indicated a number of unusual proteolytic cleavage sites suggesting the presence of unknown proprotein convertases.

An important contribution to the variability of any proteome is given by the time dimension that should be carefully considered to define physiological modifications. To this purpose, whole saliva proteome was investigated in a wide age range. Whole saliva was collected from 17 preterm newborns with a postconceptional age at birth of 178-217 days. In these subjects sample collection was performed serially starting immediately after birth and within about 1 year follow-up, gathering a total of 111 specimens. Furthermore, whole saliva was collected from 182 subjects aged between 0 and 17 years and from 23 adults aged between 27 and 57 years. The naturally occurring intact salivary proteome of the 316 samples was analyzed by low- and high-resolution HPLC-ESI-MS platforms. Proteins peculiar of the adults appeared in saliva with different time courses during human development. Acidic proline-rich proteins encoded by PRH2 locus and glycosylated basic proline-rich proteins encoded by PRB3 locus appeared following 180 days of postconceptional age, followed at 7 months (+/- 2 weeks) by histatin 1, statherin, and P-B peptide. The other histatins and acidic proline-rich proteins encoded by PRH1 locus appeared in whole saliva of babies from 1 to 3 weeks after the normal term of delivery, S-type cystatins appeared at 1 year (+/- 3 months), and basic proline-rich proteins appeared at 4 years (+/- 1 year) of age. All of the proteinases involved in the maturation of salivary proteins were more active in preterm than in at-term newborns, on the basis of the truncated forms detected. The activity of the Fam20C kinase, involved in the phosphorylation of various proteins, started around 180 days of postconceptional age, slowly increased reaching values comparable to adults at about 2 years (+/- 6 months) of age. Instead, MAPK14 involved in the phosphorylation of S100A9 was fully active since birth also in preterm newborns.

In this study, we investigated whether vestibular evoked myogenic potentials (VEMPs) and dynamic posturography (DP) are useful in the evaluation of the vestibular function in patients affected by active monoaural Menière's disease (MD) treated with intratympanic gentamycin. Twelve subjects affected by monoaural MD were treated with weekly intratympanic injections of 0.5 ml of gentamycin at a concentration of 20 mg/ml. VEMPs were used to test saccular function, while postural control was analyzed by DP. The results obtained with these two techniques were compared with those obtained by using bithermal caloric test. The mean follow-up was 15.3 months (6–28 months). Therapy resulted in complete absence of the caloric response in six subjects (50) and in caloric test-induced asymmetry in the remaining individuals, ranging from 83 to 27. At follow-up, eleven patients (91.6%) were free of vertigo, while one patient had two vertigo spells 9 months after treatment. Before treatment, VEMPs were present in the affected ear of eleven patients. After treatment VEMPs were absent in all the patients. At the end of follow-up, reappearance of VEMPs was observed in two patients, with no changes in latency values and amplitude ratio. DP demonstrated a reduction of the Composite Score (CS) one week after therapy, with a prevalent reduction of the vestibular component. After 6 months, there was an improvement of the CS and, in particular, of the vestibular component. The present study demonstrates that bithermal caloric test and VEMPs allow for the functional evaluation of both the horizontal semicircular canal and the sacculus, suggesting that these techniques might be used together to monitor the efficacy of intratympanic gentamycin therapy. In addition, our data indicate that DP might provide important information on compensation phenomena and show that intratympanic gentamycin can improve postural control in MD patients.

Objective: Whiplash is an acceleration-deceleration mechanism of energy transfer to the neck that may result from a rear-end or side impact, predominantly in motor vehicle accidents but also from other mishaps. Vertigo and dizziness after whiplash injury are the most frequent, persistent and disabling symptoms, even in the absence of anatomical and cervical spine damage. Vestibular disturbances in whiplash patients have been widely investigated; nevertheless, physiopathology of vertigo and dizziness still remains an unsolved problem. The aim of our study was to demonstrate that cVEMPs (cervical Vestibular Evoked Myogenic Potentials) represent a valid and non-invasive technique able to investigate vestibular function, in particular the vestibulo-collic reflex and macular function. Study design: We examined 25 patients affected by disabling post-whiplash injury by means of audiovestibular tests: audiometric and impedance tests, nystagmus evaluation, caloric test, dynamic posturography and cervical V...

Proteomic platforms can be classified in bottom-up strategies, which analyze the sample after proteolytic digestion, and top-down strategies, which analyze the intact naturally occurring proteome. Bottom-up platforms are high-throughput because they can investigate a large number of proteins, regardless of their dimension. Nonetheless, information on post-translational modifications (PTMs) can be lost, especially those regarding naturally occurring cleavages and alternative splicing. Top-down platforms cannot cover vast proteomes, however, they can disclose subtle structural variations occurring during protein maturation and allow label-free relative quantifications in an unlimited number of samples. A repertoire of 256 masses belonging to naturally occurring proteins and peptides consistently detected by RP-HPLC-ESI-MS analysis of the acidic soluble fraction of human whole saliva is presented in this study. Of them, 233 have been identified, while 23 are still pending for the definitive characterization. The present review reports average and mono-isotopic masses of the peptides and proteins detected, RP-HPLC elution times, PTMs, origin and quali-quantitative variations observed in several physiological and pathological conditions. The information reported can be a reference for users of top-down RP-HPLC-ESI-MS proteomic platforms applied to the study of the human salivary proteome as well as of other human bodily fluids.

This study describes the identification and structural characterization of Sus scrofa statherin. HPLC-electrospray ionization mass spectrometry analysis on pig parotid secretory granule extracts evidenced a peptide with a molecular mass value of 5381.1 +/- 0.6 Da and its truncated form, devoid of the C-terminal Ala residue, with a molecular mass value of 5310.1 +/- 0.6 Da. The complete sequence of pig statherin gene was determined by sequencing the full-length cDNA obtained by rapid amplification of cDNA ends. The gene is 549 base pairs long and contains an open reading frame of 185 nucleotides, encoding a 42-amino acid secretory polypeptide with a signal peptide of 19 residues. This sequence presents some typical features of the four statherins characterized till now, showing the highest degree of amino acid identity with bovine (57%) and human statherin (39%). Pig statherin is mono-phoshorylated on Ser-3, while primate statherins already characterized are di-phosphorylated on Ser-2 and Ser-3. This difference, probably connected to the Asp-4 --Glu substitution, suggests the involvement of the Golgi-casein kinase, which strictly recognizes the SX(E/pS) consensus sequence.

The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS) also in noise induced hearing loss (NIHL) and anti-oxidants and free-radicals scavengers have been shown to attenuate the damage. Coenzyme Q(10) (CoQ(10)) or ubiquinone has a bioenergetic role as a component of the mithocondrial respiratory chain, it inhibits mitochondrial lipid peroxidation, inducing ATP production and it is involved in ROS removal and prevention of oxidative stress-induced apoptosis. However the therapeutic application of CoQ(10) is limited by the lack of solubility and poor bio- availability, therefore it is a challenge to improve its water solubility in order to ameliorate the efficacy in tissues and fluids. This study was conducted in a model of acoustic trauma in the guinea pig where the effectiveness of CoQ(10) was compared with a soluble formulation of CoQ(10) (multicomposite CoQ(10) Terclatrate, Q-ter) given intraperitoneally 1 h before and once daily for 3 days after pure tone noise exposure (6 kHz for 1 h at 120 dB SPL). Functional and morphological studies were carried out by measuring auditory brainstem responses, scanning electron microscopy for hair cell loss count, active caspase 3 staining and terminal deoxynucleotidyl transferase-mediated dUTP labelling assay in order to identify initial signs of apoptosis. Treatments decreased active caspase 3 expression and the number of apoptotic cells, but animals injected with Q-ter showed a greater degree of activity in preventing apoptosis and thus in improving hearing. These data confirm that solubility of Coenzyme Q(10) improves the ability of CoQ(10) in preventing oxidative injuries that result from mitochondrial dysfunction.

This work reports the successful recombinant expression of human statherin in Escherichia coli , its purification and in vitro phosphorylation. Human statherin is a 43-residue peptide, secreted by parotid and submandibular glands and phosphorylated on serine 2 and 3. The codon-optimized statherin gene was synthesized and cloned into commercial pTYB11 plasmid to allow expression of statherin as a fusion protein with intein containing a chitin-binding domain. The plasmid was transformed into E. coli strains and cultured in Luria–Bertani medium, which gave productivity of soluble statherin fusion protein of up to 47 mg per liter of cell culture, while 112 mg of fusion protein were in the form of inclusion bodies. No significant refolded target protein was obtained from inclusion bodies. The amount of r-h-statherin purified by RP–HPLC corresponded to 0.6 mg per liter of cell culture. Attenuated total reflection-Fourier transform infrared spectroscopy experiments performed on human statherin isolated from saliva and r-h-statherin assessed the correct folding of the recombinant peptide. Recombinant statherin was transformed into the diphosphorylated biologically active form by in vitro phosphorylation using the Golgi-enriched fraction of pig parotid gland containing the Golgi-casein kinase.

Thymosin beta(4) (Tbeta(4)), its sulfoxide, and thymosin beta(10 )(Tbeta(10)) were detected in human saliva and identified by different strategies based on RP HPLC coupled to electrospray multidimensional IT MS. Tbeta(4 )was almost always detected in whole saliva, its sulfoxide sporadically, Tbeta(10) rarely. Tbeta(4) was undetectable in parotid saliva and less concentrated in submandibular/sublingual saliva than in whole saliva. Analysis of gingival crevicular fluid revealed high relative amounts of Tbeta(4), Tbeta(4) sulfoxide, and Tbeta(10) in all the samples. Tbeta(4) mean concentration was 200 times higher in crevicular fluid (20 micromol/L, N = 9) than in whole saliva (0.1 micromol/L, N = 9). Crevicular fluid concentration of Tbeta(4 )(ca. 5% represented by its sulfoxide) and beta(10 )significantly correlated (r = 0.856; N = 9), and their ratio was about 5. A significant correlation was also observed between Tbeta(4 )concentrations in whole saliva and gingival crevicular fluid (r = 0.738; N = 9). Immunohistochemical analysis of the major salivary glands showed that immunoreactivity for Tbeta(4) is restricted to ductal cells, with minor degree of focal positivity in some acinar cells. On the whole, results indicate that gingival sulcus is a main, although not the sole, source for oral Tbeta(4 )and Tbeta(10).

Summary Objective The aim of this work is to establish if the vestibular evoked myogenic potentials (VEMPs) could be used as a clinical test of vestibular function in children. Materials and methods Forty normal hearing children, aged between 3 and 15 years, and classified in preschool and scholar group, have been investigated in order to study normal development of vestibular potentials and to define fundamental parameters of VEMPs, establishing normal data of latencies and amplitude ratio. Electromyographic activity of sternocleidomastoid muscle was recorded while children were laid supine on a bed and asked to raise their head off of the bed in order to activate their neck flexors bilaterally. The saccular receptors were acoustically stimulated with a logon of 500 Hz at an intensity of 130 dB peSPL presented monaurally through earphones. In each recording, we analysed latencies and amplitudes of the p13 and n23 waves and the amplitude ratio between the two ears. Results VEMPs were normally detected in all subjects. In preschool group mean p13 and mean n23 latencies were, respectively, 16.13 (±2.12) ms and 21.17 (±2.77) ms; mean amplitude ratio was 28.49 (±18.10). In scholar group mean p13 and n23 were respectively 16.14 (±3.48) ms and 21.78 (±3.39) ms, while mean amplitude ratio 20.44 (±13.24). Comparison of latencies and amplitude ratio between the children groups and control adult group did not showed any significant differences. Conclusion In conclusion, VEMPs could represent a valid and non-invasive technique able to investigate vestibular function in children and, in particular, vestibulo collic reflex.

Objective: The aim of this study was to measure concentration of human salivary statherin in patients with oral cavity pathologies and salivary gland diseases. Subjects and methods: Levels of statherin were analysed with High Performance Liquid Chromatography (HPLC) in following groups of subjects: group A: 24 patients with neoplastic diseases of salivary glands, group B: 13 patients with inflammatory lesions of salivary glands, group C: 13 patients with precancerous and cancerous lesions of the oral cavity excluding salivary gland tumors, group D: 20 healthy volunteers (control group). Results: Our preliminary data indicated a sensible reduction of the statherin level in the saliva of patients with precancerous and cancerous lesions of the oral cavity (group C) compared with the healthy subjects (group D). The statherin levels are not significantly reduced either in the inflammatory (group B) or in the salivary glands tumours (group A), compared with the healthy subjects (group D). Conclusion: Statherin could play a protective effect in oral cavity in association with its other functions.

Objective To assess clinical safety and efficacy of the erbium: yttrium-aluminum-garnet (Er:YAG) laser in the stapes surgery; to define and optimize parameters that render the procedure safe for the inner ear. Study design Retrospective study. Material and methods A microscope-integrated Er:YAG laser stapedotomy was performed on 29 patients and a conventional stapedotomy on 41 patients. An early (within 1 to 3 days after stapes surgery) and late (at least 6 weeks) pure-tone bone-conduction threshold audiogram was obtained. Results No statistically significant differences were found by Student’s t test over all measured frequencies between pre- and postoperative bone-conduction thresholds in each group. There was no statistically significant difference for all frequencies between early (3 days) and late postoperative mean bone-conduction thresholds. Conclusions The results of our preliminary clinical study showed that erbium laser poses no risk to inner ear function. However, the lack of standardization obliges further investigation to establish safe clinical parameters of the Er:YAG laser. EBM rating B-3