Effectiveness of bismuth subgallate for preventing bleeding following adenotonsillectomy: A multicentre study.

BACKGROUND: Tonsillectomy and adenotonsillectomy are surgical procedures routinely performed worldwide, with various complications, including postoperative bleeding (PTH). Among haemostatic agents, bismuth subgallate (BS) has been employed in the past decades, but its use is controversial in children. OBJECTIVE: This retrospective, multicentre study aims to evaluate the effectiveness and safety of BS in preventing PTH following tonsillectomy and adenotonsillectomy. MATERIALS AND METHODS: Two cohorts of children between 0 and 18 years of age were compared in two different hospitals. The first (active) group of patients included children who underwent tonsillectomy/adenotonsillectomy performed using BS added to gauze swabs, whereas this agent was not administered to the second (control) group. The following variables were analysed: age, gender, degree of tonsillar hyperplasia, length of hospital stay, acute complications (including bleeding and infection), further admissions to the Paediatric Emergency Department (PED), and further hospital admissions in the 30 days postoperatively. RESULTS: Four-thousand- seven hundred forty-four children were included in the study, 2598 in the active group and 2146 in the control group. The cases included in the active treatment group displayed a significantly reduced PTH prevalence, 1.4 versus 2.6 % (p < 0.05). No cases of neurological complications or aspiration pneumonia were detected. CONCLUSIONS: This study supports BS as a safe and reliable option for preventing severe PTH following tonsillectomy/adenotonsillectomy.

Proteomic Study Identifies Glycolytic and Inflammation Pathways Involved in Recurrent Otitis Media.

Recurrent acute otitis media (RAOM) in children is clinically defined as the occurrence of at least three episodes of acute otitis media over a course of 6 months. A further common pathological condition of interest in the context of pediatric otolaryngology is adenotonsillar hypertrophy (ATH), a common cause of obstructive sleep apnea syndrome. Aimed at unraveling the differential modulation of proteins in the two pathologies and at understanding the possible pathways involved in their onset, we analyzed the proteomic profile of the adenoids from 14 RAOM and ATH patients by using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). The 2-DE coupled with MS allowed us to identify 23 spots with significant (p-value < 0.05) changes in protein amount, recognizing proteins involved in neutrophil degranulation and glycolysis pathways.

Peak grain forecasts for the US High Plains amid withering waters.

Irrigated agriculture contributes 40% of total global food production. In the US High Plains, which produces more than 50 million tons per year of grain, as much as 90% of irrigation originates from groundwater resources, including the Ogallala aquifer. In parts of the High Plains, groundwater resources are being depleted so rapidly that they are considered nonrenewable, compromising food security. When groundwater becomes scarce, groundwater withdrawals peak, causing a subsequent peak in crop production. Previous descriptions of finite natural resource depletion have utilized the Hubbert curve. By coupling the dynamics of groundwater pumping, recharge, and crop production, Hubbert-like curves emerge, responding to the linked variations in groundwater pumping and grain production. On a state level, this approach predicted when groundwater withdrawal and grain production peaked and the lag between them. The lags increased with the adoption of efficient irrigation practices and higher recharge rates. Results indicate that, in Texas, withdrawals peaked in 1966, followed by a peak in grain production 9 y later. After better irrigation technologies were adopted, the lag increased to 15 y from 1997 to 2012. In Kansas, where these technologies were employed concurrently with the rise of irrigated grain production, this lag was predicted to be 24 y starting in 1994. In Nebraska, grain production is projected to continue rising through 2050 because of high recharge rates. While Texas and Nebraska had equal irrigated output in 1975, by 2050, it is projected that Nebraska will have almost 10 times the groundwater-based production of Texas.

Combined intranasal fentanyl and dexmedetomidine plus inhaled nitrous oxide sedation in children needing myringotomy and ventilation tube insertion with a specific handheld device.

OBJECTIVES: We report a case series of one-time 4 mcg/kg dose of intranasal dexmedetomidine and 1 mcg/kg of intranasal fentanyl plus inhaled nitrous oxide for procedural sedation in children with otitis media with effusion (OME) for tympanostomy tube placement with a specific handheld device (Solo TTD, AventaMed ®). METHODS: A retrospective review was conducted in a tertiary paediatric teaching hospital on patients with OME referred from December 2018 to December 2019 in need of procedural sedation for myringotomy and ventilation tube insertion (VTI). Sixteen of twenty-four consecutively admitted subjects received a one-time dose (4 mcg/kg) of intranasal dexmedetomidine and 1mcg/Kg of intranasal fentanyl followed by inhaled nitrous oxide (iN2O) at 50% with the intended goal to achieve a Ramsay Sedation Score 4 allowing a motionless procedure with adequate analgesia. Parents' satisfaction for the procedure was measured by mean of a Likert scale (from 0 to 5 points). RESULTS: Sixteen patients underwent procedural sedation for myringotomy with VTI. Sedation was achieved successfully in fifteen patients (93,75%), with a mean induction time of 29 min (range 19-43) and a mean recovery time of 74 min (range 54-110). The patient who did reach an adequate sedation level underwent an intravenous line positioning and a dose of ketamine. No adverse effects were reported, and the parents' judgment average on the Likert scale was 4,93. VTI procedure was successful in all ears. CONCLUSIONS: A combination of intranasal dexmedetomidine, fentanyl, and iN2O could be considered as a possible option for procedural sedation in children with OME undergoing procedural sedation for tympanostomy tube placement in children with Solo TTD device.

Copy number variation, gene expression and histological localization of human beta-defensin 2 in patients with adeno-tonsillar hypertrophy.

Both bacterial infections and innate oral immunity response participate in development of adeno-tonsillar hypertrophy (ATH). ATH can lead to obstructive sleep apnea. We investigated the beta-defensin 2 (hBD-2) encoding gene, DEFB4, by analyzing the copy number variations (CNVs) of the defensin gene cluster in patients with ATH and by correlating CNV with DEFB4 gene expression. We enrolled 79 patients with ATH, 21 of whom presented with only adenoid hypertrophy, while 58 exhibited hypertrophy of both adenoid and tonsil. CNVs of the defensin gene cluster, DEFB4 mRNA, and hBD-2 protein expression were assessed. Also, beta-defensin 2 was localized histologically using immunohistochemistry. The distribution of defensin gene cluster CNV was similar among the 79 subjects. DEFB4 expression analysis exhibited considerable inter-individual variability, but with neither specific differences among subjects nor correlation with the CNV number. Immunohistochemistry enabled localization of hBD-2 in the tonsil and adenoid epithelium. No differences in localization between the two ATH presentations were found. Inducible antimicrobial defensin peptides exhibited great inter-individual variability in terms of both CNV and gene expression, but no correlation with presentation of ATH was found.

Human beta defensin-1 is involved in the susceptibility to adeno-tonsillar hypertrophy.

INTRODUCTION: Innate immunity molecules are known to play a pivotal role in the homeostasis of the oral mucosa, permitting the presence of commensal microflora and, at the same time, providing a first line of defense against pathogens attempting to invade the oral cavity. Tonsils represent the local immune tissue in oral cavity, being able to provide a non-specific response to pathogens; however, in the presence of microbes or foreign materials present in the mouth tonsils could became infected and develop chronic inflammation, thus leading to hypertrophy. The etiology of the disease is multifactorial depending upon environmental and host factors, the latter including molecules of mucosal innate immunity. METHODS: Ninety-five children with adeno-tonsillar hypertrophy subjected to adeno-tonsillectomy were recruited at the pediatric otorhinolaryngology service of the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste (Italy). The specimen discarded from the surgery were used for genomic DNA extraction and genotyping, for mRNA extraction and gene expression analysis, finally the samples were cut and used to prepare slides to perform immunohistochemistry. RESULTS: Functional polymorphisms within DEFB1 gene, encoding the human beta defensin-1 (hBD-1), were analyzed finding association between DEFB1 rare haplotypes and susceptibility to adeno-tonsillar hypertrophy. DEFB1 mRNA expression was detected in the tonsils and the hBD-1 protein was localized at the epithelia of tonsils mainly in the proximity of the basal lamina. CONCLUSION: Our findings lead us to hypothesize an involvement of hBD-1 mediated innate immunity in the modulation of the susceptibility towards adeno-tonsillar hypertrophy development.

Neither hereditary periodic fever nor periodic fever, aphthae, pharingitis, adenitis: Undifferentiated periodic fever in a tertiary pediatric center.

AIM: To describe the frequency and clinical characteristics of patients with undifferentiated periodic fever (UPF) and to investigate whether a clinical classification of UPF based on the PRINTO-Eurofever score can help predicting the response to treatment and the outcome at follow-up. METHODS: Clinical and therapeutic information of patients with recurrent fever who presented at a single pediatric rheumatology center from January 2006 through April 2016 were retrospectively collected. Patients with a clinical suspicion of hereditary periodic fever (HPF) syndrome and patients with clinical picture of periodic fever, aphthae, pharingitis, adenitis (PFAPA) who were refractory to tonsillectomy underwent molecular analysis of five HPF-related genes: MEFV (NM_000243.2), MVK (NM_000431.3), TNFRSF1A (NM_001065.3), NLRP3 (NM_001079821.2), NLRP12 (NM_001277126.1). All patients who had a negative genetic result were defined as UPF and further investigated. PRINTO-Eurofever score for clinical diagnosis of HPF was calculated in all cases. RESULTS: Of the 221 patients evaluated for periodic fever, twelve subjects with a clinical picture of PFAPA who were refractory to tonsillectomy and 22 subjects with a clinical suspicion of HPF underwent genetic analysis. Twenty-three patients (10.4%) resulted negative and were classified as UPF. The median age at presentation of patients with UPF was 9.5 mo (IQR 4-24). Patients with UPF had a higher frequency of aphthae (52.2% vs 0%, P = 0.0026) and musculoskeletal pain (65.2% vs 18.2%, P = 0.0255) than patients with genetic confirmed HPF. Also, patients with UPF had a higher frequency of aphthous stomatitis (52.2% vs 10.7%, P < 0.0001), musculoskeletal pain (65.2% vs 8,0%, P < 0.0001), and abdominal pain (52.2% vs 4.8%, P < 0.0001) and a lower frequency of pharyngitis (56.6% vs 81.3%, P = 0.0127) compared with typical PFAPA in the same cohort. Twenty-one of 23 patients with UPF (91.3%) received steroids, being effective in 16; 13 (56.2%) were given colchicine, which was effective in 6. Symptoms resolution occurred in 2 patients with UPF at last follow-up. Classification according to the PRINTO-Eurofever score did not correlate with treatment response and prognosis. CONCLUSION: UPF is not a rare diagnosis among patients with periodic fever. Clinical presentation place UPF half way on a clinical spectrum between PFAPA and HPF. The PRINTO-Eurofever score is not useful to predict clinical outcome and treatment response in these patients.

Lactoferrin gene polymorphisms in Italian patients with recurrent tonsillitis.

INTRODUCTION: Recurrent tonsillitis is an oral pathology characterized by inflammation of tonsils. The disease susceptibility depends upon environmental and host factors, specifically the innate immune response, the first line of host defence could play an important role. Among innate immunity members, lactoferrin, known for its antimicrobial properties, was previously correlated with the risk of oral pathology as periodontitis and dental caries. METHODS: 89 Italian children presenting recurrent tonsillitis and 95 healthy children were genotyped for two LTF non-synonymous polymorphisms, called Thr29Ala and Arg47Lys, in order to investigate their potential role in recurrent tonsillitis susceptibility. RESULTS: no different allele, genotype and haplotype frequency distributions were detected comparing patients and controls. CONCLUSION: data from the current study indicate that LTF polymorphisms might not be involved in recurrent tonsillitis development in our Italian population. However, since the importance of lactoferrin in oral immunity has been previously assessed, further studies should be necessary to unravel the potential role of LTF genetic variants in oral cavity.

DEFB1 polymorphisms and susceptibility to recurrent tonsillitis in Italian children.

INTRODUCTION: The tonsils are secondary lymphoid organs fundamental for immune system response against pathogens within the oral cavity. Tonsillitis refers to inflammation of the pharyngeal tonsils that may include the adenoids and the lingual tonsils and that can be acute, recurrent, and chronic. Viral or bacterial infections, as well as immunologic factors are the main trigger to tonsillitis and disease's chronicity: the host immune responses, especially the innate one, could play an important role in susceptibility to the disease. OBJECTIVES: The current study aims at investigating the role of functional polymorphisms in the 5'UTR (c.-52G>A, c.-44G>C and c.-20G>A) of DEFB1 gene, encoding for the antimicrobial peptide human beta-defensin 1, in the predisposition to recurrent tonsillitis in children from North Eastern Italy. RESULTS: No significant correlation was found between DEFB1 allele, genotype and haplotype frequencies and recurrent tonsillitis susceptibility with the exception of an increased risk to disease development in patients carrying DEFB1 rare haplotypes. CONCLUSION: Our results may suggest that DEFB1 polymorphisms alone may not influence pathology susceptibility, however they could possibly concur, together with other factors involved in the genetic control of innate immune system, in the predisposition towards recurrent tonsillitis.

Ear nose throat manifestations in hypoidrotic ectodermal dysplasia.

The ectodermal dysplasias (EDs) are a large and complex group of inherited disorders. In various combinations, they all share anomalies in ectodermal derived structures: hair, teeth, nails and sweat gland function. Clinical overlap is present among EDs. Few causative genes have been identified, to date. Altered gene expression is not limited to the ectoderm but a concomitant effect on developing mesenchymal structures, with modification of ectodermal-mesenchymal signaling, takes place. The two major categories of ED include the hidrotic and hypohidrotic form, the latter more frequent; they differentiate each other for the presence or absence of sweat glands. We report Ear Nose Throat manifestations of ED, linked to the reduction of mucous glands in the nasal fossae with reduced ciliar function, and decrease salivary glands function. Often patients report an increased rate of infections of the upper respiratory tract and of the ear. Nasal obstruction due to the presence of nasal crusting, hearing loss and throat hoarseness are the most represented symptoms. Environmental measures, including a correct air temperature and humidification, is mandatory above all in subjects affected by hypohidrotic form.

Burden of disease caused by otitis media: systematic review and global estimates.

BACKGROUND: Otitis media (OM) is a leading cause of health care visits and drugs prescription. Its complications and sequelae are important causes of preventable hearing loss, particularly in developing countries. Within the Global Burden of Diseases, Injuries, and Risk Factors Study, for the year 2005 we estimated the incidence of acute OM, chronic suppurative OM, and related hearing loss and mortality for all ages and the 21 WHO regional areas. METHODS: We identified risk factors, complications and sequelae of OM. We carried out an extensive literature review (Medline, Embase, Lilacs and Wholis) which lead to the selection of 114 papers comprising relevant data. Data were available from 15 of the 21 WHO regions. To estimate incidence and prevalence for all countries we adopted a two stage approach based on risk factors formulas and regression modelling. RESULTS: Acute OM incidence rate is 10.85% i.e. 709 million cases each year with 51% of these occurring in under-fives. Chronic suppurative OM incidence rate is 4.76 ‰ i.e. 31 million cases, with 22.6% of cases occurring annually in under-fives. OM-related hearing impairment has a prevalence of 30.82 per ten-thousand. Each year 21 thousand people die due to complications of OM. CONCLUSIONS: Our study is the first attempt to systematically review the available information and provide global estimates for OM and related conditions. The overall burden deriving from AOM, CSOM and their sequelae is considerable, particularly in the first five years of life and in the poorest countries. The findings call for incorporating OM-focused action within preventive and case management strategies, with emphasis on the more affected.

Interactions of two O-phosphorylresveratrol derivatives with model membranes.

The hydrosoluble resveratrol derivative 3-O-phosphorylresveratrol was shown to be more cytotoxic against DU 145 prostate cancer cells than its analog 4'-O-phosphorylresveratrol. In an attempt to unveil the molecular determinants that lye at the root of their different biological effects, here we investigate the interactions of the two resveratrol derivatives with DMPC model membranes by using DSC, membrane permeation/poration assays and molecular dynamics. The results show that the 3-O-derivative interacts with DMPC membranes and diffuses across them. The 4'-O-derivative lies preferentially onto the surface of membrane. The MD simulations provide a molecular interpretation of the experiments and highlight that, in order to maximize the apolar interactions, the 3-O-derivative is embedded in the lipid hydrophobic region. This topographical position of the 3-O resveratrol analog perturbs the liquid-crystalline order of the lipid bilayer promoting membrane curvature and partial lipid loss from the vesicle. This finding reconciles with the lowering of the enthalpy of the lipid phase transition and the ability of the molecule to diffuse across membranes. The present data contribute to explain the different biological activity of the two molecules and evidence that membrane permeability is a key requirement for effective design of resveratrol derivatives to be used for therapeutic purposes.

Non-invasive assessment of hemispheric language dominance by optical topography during a brief passive listening test: a pilot study.

BACKGROUND: The Wada test is usually used for pre-surgical assessment of language lateralization. Considering its invasiveness and risk of complications, alternative methods have been proposed but they are not always applicable to non-cooperative patients. In this study we explored the possibility of using optical topography (OT)--a multichannel near-infrared system--for non-invasive assessment of hemispheric language dominance during passive listening. MATERIAL/METHODS: Cortical activity was monitored in a sample of healthy, adult Italian native speakers, all right-handed. We assessed changes in oxy-haemoglobin concentration in temporal, parietal and posterior frontal lobes during a passive listening of bi-syllabic words and vowel-consonant-vowel syllables lasting less then 3 minutes. Activated channels were identified by t tests. RESULTS: Left hemisphere showed significant activity only during the passive listening of bi-syllabic words. Specifically, the superior temporal gyrus, the supramarginal gyrus and the posterior inferior parietal lobe were activated. CONCLUSIONS: During passive listening of bi-syllabic words, right handed healthy adults showed a significant activation in areas already known to be involved in speech comprehension. Although more research is needed, OT proved to be a promising alternative to the Wada test for non-invasive assessment of hemispheric language lateralization, even if using a particularly brief trial, which has been designed for future applications with non-cooperative subjects.

The role of aromatic side-chains in amyloid growth and membrane interaction of the islet amyloid polypeptide fragment LANFLVH.

Human islet amyloid polypeptide (hIAPP) is known to misfold and aggregate into amyloid deposits that may be found in pancreatic tissues of patients affected by type 2 diabetes. Recent studies have shown that the highly amyloidogenic peptide LANFLVH, corresponding the N-terminal 12-18 region of IAPP, does not induce membrane damage. Here we assess the role played by the aromatic residue Phe in driving both amyloid formation and membrane interaction of LANFLVH. To this aim, a set of variant heptapeptides in which the aromatic residue Phe has been substituted with a Leu and Ala is studied. Differential scanning calorimetry (DSC) and membrane-leakage experiments demonstrated that Phe substitution noticeably affects the peptide-induced changes in the thermotropic properties of the lipid bilayer but not its membrane damaging potential. Atomic force microscopy (AFM), ThT fluorescence and Congo red birefringence assays evidenced that the Phe residue is not required for fibrillogenesis, but it can influence the self-assembling kinetics. Molecular dynamics simulations have paralleled the outcome of the experimental trials also providing informative details about the structure of the different peptide assemblies. These results support a general theory suggesting that aromatic residues, although capable of affecting the self-assembly kinetics of small peptides and peptide-membrane interactions, are not essential either for amyloid formation or membrane leakage, and indicate that other factors such as ß-sheet propensity, size and hydrophobicity of the side chain act synergistically to determine peptide properties.