Adenotonsillectomy in children with recurrent acute tonsillitis: review and implications for practice

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C to U Editing Stimulates A to I Editing in the Anticodon Loop of a Cytoplasmic Threonyl tRNA in Trypanosoma brucei

Editing of tRNAs is widespread in nature and either changes the decoding properties or restores the folding of a tRNA. Unlike the phylogenetically disperse adenosine (A) to inosine (I) editing, cytosine (C) to uridine (U) editing has only been previously described in organellar tRNAs. We have shown that cytoplasmic tRNAThr(AGU) undergoes two distinct editing events in the anticodon loop: C to U and A to I. In vivo, every inosine-containing tRNAThr is also C to U edited at position 32. In vitro, C to U editing stimulates conversion of A to I at the wobble base. Although the in vivo and in vitro requirements differ, in both cases, the C to U change plays a key role in A to I editing. Due to an unusual abundance of A34-containing tRNAs, our results also suggest that the unedited and edited tRNAs are functional, each dedicated to decoding a specific threonine codon. C to U editing of cytoplasmic tRNA expands the editing repertoire in eukaryotic cells, and when coupled to A to I changes, leads to an interrelation between editing sites

Topically administered hyaluronic acid in the upper airway: A narrative review

Hyaluronic acid plays a role in controlling inflammatory airway processes and mucociliary clearance, and it is also involved in tissue healing and remodelling. Some studies have tested the effectiveness of topically administered hyaluronic acid in patients with upper airway diseases with positive preliminary results. This article describes the use of topically administered hyaluronic acid in patients with otolaryngological disorders. Pertinent studies published between January 2000 and October 2016 were selected by means of a MEDLINE search using the following terms: \u2018hyaluronic acid\u2019 and \u2018otolaryngology\u2019, \u2018otitis\u2019, \u2018pharyngitis\u2019, \u2018tonsillitis\u2019, \u2018rhinitis\u2019, \u2018rhinosinusitis\u2019 and \u149ose\u2019. Twelve of the 19 initially identified papers were selected, corresponding to 902 patients as a whole. There is some evidence that topically administered hyaluronic acid is effective or moderately effective in different otolaryngological conditions, as it improves the global subjective and clinical status of patients with inflammation of the nasopharyngeal and oto-tubaric complex, those with rhinitis or rhinosinusitis and those who have undergone nasal and sinonasal surgery. However, these findings should be viewed cautiously as they are based on a limited number of studies, some of which were probably under-powered because of their small patient samples

Synthesis, Antitumor and Antiviral In Vitro Activities of New Benzotriazole-Dicarboxamide Derivatives

Cancer and viral infections continue to threaten humankind causing death worldwide. Hence, the discovery of new anticancer and antiviral agents still represents a major scientific goal. Heterocycles designed to mimic the chemical structure of natural pyrimidines and purines have been designed over the years, exerting their activity acting as false substrates on several different targets. We reported a series of bis-benzotriazole-dicarboxamide derivatives which inhibit viral helicase of poliovirus, and hence we planned structure modifications to obtain different series of new dicarboxamides. Here, the synthesis and characterization of 56 new compounds: 31 bis-benzotriazole dicarboxamides and 25 mono-substituted acidic derivatives are reported. The synthesized compounds were tested for their antiviral and antitumor activity. Mostly, compounds 4a, 4c and 4d showed antiviral activity against tested Picornaviruses, Coxsackievirus B5 and Poliovirus-1. Likewise, four derivatives (3b, 3d, 4d, 9b) showed notable antiproliferative activity inhibiting cell growth in two distinct antitumor screenings. Compound 3b was selected as the antitumor lead compound for the wide range of activity and the potency proved. The lead compound was proved to induce apoptosis in SK-MES1 tumor cells, in a dose-dependent manner

Supervised nasal saline irrigations in otitis-prone children

Objectives: To retrospectively investigate the impact of supervised daily nasal saline irrigations (NSI) with 0. 9% saline solution in children with a history of recurrent acute otitis media (RAOM). Methods: A retrospective pilot study was planned to evaluate the possible effect of supervised NSI in reducing the number of acute otitis media (AOM) episodes in otitis-prone children aged 1-5 years, compared to children not instructed to correct NSI performance. Results: Analysis was based on the data contained in 173 charts (57.3% males, mean age of 30.9 \ub1 7.3 months). 52.0% of children had not been instructed to perform NSI, while the remaining (48.0%) patients had received supervised NSI. At the 4-months follow-up visit a significant reduced number of AOM episodes (1.03 \ub1 0.14 vs. 2.08 \ub1 0.16; p < 0.001) as well as antibiotic treatments (1.48 \ub1 0.17 vs. 2.59 \ub1 0.18; p < 0.001) was documented in children receiving supervised NSI compared to those not instructed for NSI performance. Conclusions: These data suggest that NSI should be considered in the therapeutic management of children with RAOM, and should be routinely prescribed as a daily adjunctive treatment to reduce acute infectious exacerbations in otitis-prone patients. Accurate parents training is crucial in order to improve children compliance and treatment effectiveness

Sinonasal-Related Orbital Infections in Children: A Clinical and Therapeutic Overview

Sinonasal-related orbital infections (SROIs) are typically pediatric diseases that occur in 3\u20134% of children with acute rhinosinusitis. They are characterised by various clinical manifestations, such as peri-orbital and orbital cellulitis or orbital and sub-periosteal abscesses that may develop anteriorly or posteriorly to the orbital septum. Posterior septal complications are particularly dangerous, as they may lead to visual loss and life-threatening events, such as an intracranial abscess and cavernous sinus thrombosis. Given the possible risk of permanent visual loss due to optic neuritis or orbital nerve ischemia, SROIs are considered ophthalmic emergencies that need to be promptly recognised and treated in an urgent-care setting. The key to obtaining better clinical outcomes in children with SROIs is a multi-disciplinary assessment by pediatricians, otolaryngologists, ophthalmologists, radiologists, and in selected cases, neurosurgeons, neurologists, and infectious disease specialists. The aim of this paper is to provide an overview of the pathogenesis, clinical manifestations, diagnosis, and treatment of pediatric SROIs, and to make some practical recommendations for attending clinicians

Crystal polymorphism in fragment-based lead discovery of ligands of the catalytic domain of UGGT, the glycoprotein folding quality control checkpoint

None of the current data processing pipelines for X-ray crystallography fragment-based lead discovery (FBLD) consults all the information available when deciding on the lattice and symmetry (i.e., the polymorph) of each soaked crystal. Often, X-ray crystallography FBLD pipelines either choose the polymorph based on cell volume and point-group symmetry of the X-ray diffraction data or leave polymorph attribution to manual intervention on the part of the user. Thus, when the FBLD crystals belong to more than one crystal polymorph, the discovery pipeline can be plagued by space group ambiguity, especially if the polymorphs at hand are variations of the same lattice and, therefore, difficult to tell apart from their morphology and/or their apparent crystal lattices and point groups. In the course of a fragment-based lead discovery effort aimed at finding ligands of the catalytic domain of UDP–glucose glycoprotein glucosyltransferase (UGGT), we encountered a mixture of trigonal crystals and pseudotrigonal triclinic crystals—with the two lattices closely related. In order to resolve that polymorphism ambiguity, we have written and described here a series of Unix shell scripts called CoALLA (crystal polymorph and ligand likelihood-based assignment). The CoALLA scripts are written in Unix shell and use autoPROC for data processing, CCP4-Dimple/REFMAC5 and BUSTER for refinement, and RHOFIT for ligand docking. The choice of the polymorph is effected by carrying out (in each of the known polymorphs) the tasks of diffraction data indexing, integration, scaling, and structural refinement. The most likely polymorph is then chosen as the one with the best structure refinement Rfree statistic. The CoALLA scripts further implement a likelihood-based ligand assignment strategy, starting with macromolecular refinement and automated water addition, followed by removal of the water molecules that appear to be fitting ligand density, and a final round of refinement after random perturbation of the refined macromolecular model, in order to obtain unbiased difference density maps for automated ligand placement. We illustrate the use of CoALLA to discriminate between H3 and P1 crystals used for an FBLD effort to find fragments binding to the catalytic domain of Chaetomium thermophilum UGGT

Phenotype Profiling and Allergy in Otitis-Prone Children

Background: Otitis-prone children can present some distinctive clinical patterns and although a number of known risk factors for recurrent acute otitis media (RAOM) are known, no dedicated epidemiological models have been developed to explain clinical heterogeneity. Methods: A preliminary retrospective pilot study was planned to evaluate the possible effect of allergic disease in the development of different disease phenotypes in otitis-prone children aged 3-10 years, particularly the absence (simple RAOM), or presence of episodes of otitis media with effusion between acute infections (RAOM with OME). Results: Analysis was based on the data contained in 153 charts (55.6% males, mean age of 59.4 \ub1 16.4 months). 75.8% of children had a simple RAOM and 24.2% a RAOM with OME. Atopy or allergy were documented in respectively 47.7 and 41.3% of children considered as a whole. The prevalence of atopy or allergy was significantly higher in the children with a RAOM with OME (atopy: 73.0 vs. 39.5%, p < 0.001; allergy: 60.0 vs. 36.1%, p = 0.049), who also more frequently showed adenoidal hypertrophy (p = 0.016), chronic adenoiditis (p = 0.007), conductive hearing loss (p = 0.004), and impaired tympanometry (p < 0.001). Conclusions: These data suggest that children with a RAOM with OME are clinically different from children with simple RAOM, as they have a more complex clinical presentation that includes not only adenoidal disease and audiological impairment, but also an underlying allergy or atopy. The possibility that the factors mentioned above may be differently involved in the heterogeneous clinical manifestations occurring in otitis-prone children needs to be further investigated in ad hoc epidemiological studies

Surgical treatment of non-tuberculous mycobacterial lymphadenitis in children: Our experience and a narrative review

Non-tuberculous mycobacterial lymphadenitis (NTML) accounts for about 95% of the cases of head-and-neck mycobacterial lymphadenitis, and its prevalence has been increasing in the Western world. The diagnostic work-up can be challenging, and differential diagnoses such as tuberculous and suppurative lymphadenitis need to be considered. It may, therefore, not be diagnosed until the disease is in a late stage, by which time it becomes locally destructive and is characterized by a chronically discharging sinus. The treatment options include a medical approach, a wait-and-see policy, and surgery, with the last being considered the treatment of choice despite the high risk of iatrogenic nerve lesions. The aim of this article is to provide an overview of pediatric, head-and-neck NTML based on the literature and our own experience, with particular emphasis on the impact and limitations of surgery