Rare Gene Mutations in Romanian Hypoacusis Patients: Case Series and a Review of the Literature.

(1) Background: In this paper, we report on three cases of hypoacusis as part of a complex phenotype and some rare gene variants. An extensive review of literature completes the newly reported clinical and genetic information. (2) Methods: The cases range from 2- to 11-year-old boys, all with a complex clinical picture and hearing impairment. In all cases, whole exome sequencing (WES) was performed, in the first case in association with mitochondrial DNA study. (3) Results: The detected variants were: two heterozygous variants in the TWNK gene, one likely pathogenic and another of uncertain clinical significance (autosomal recessive mitochondrial DNA depletion syndrome type 7-hepatocerebral type); heterozygous variants of uncertain significance PACS2 and SYT2 genes (autosomal dominant early infantile epileptic encephalopathy) and a homozygous variant of uncertain significance in SUCLG1 gene (mitochondrial DNA depletion syndrome 9). Some of these genes have never been previously reported as associated with hearing problems. (4) Conclusions: Our cases bring new insights into some rare genetic syndromes. Although the role of TWNK gene in hearing impairment is clear and accordingly reflected in published literature as well as in the present article, for the presented gene variants, a correlation to hearing problems could not yet be established and requires more scientific data. We consider that further studies are necessary for a better understanding of the role of these variants.

Prevalence of GJB2 gene mutations correlated to presence of clinical and environmental risk factors in the etiology of congenital sensorineural hearing loss of the Romanian population.

Although etiologically heterogeneous at least 50% of all early on-set hearing losses have a genetic cause and of these, the large majority, 75-80% are most probably autosomal recessive and 70% are non-syndromic. The rest of the congenital hearing losses are determined by clinical and environmental factors such as ototoxic medication, prematurity, and complications at birth. During the last decade it became clear that 50-80% of all such afflictions result from mutations in a single gene, GJB2, which encodes the protein Connexin 26. In order to, at least partially clarify this problem, especially in an emerging country such as Romania, where the problem is not studied adequately, we developed a comprehensive study of genetic, clinical and environmental risk factors for congenital hearing loss. The two most common variations of this gene, 35delG and W24X in children with positive diagnosis of bilateral severe to profound sensorineural hearing loss were investigated. A cohort of 34 children (20 female and 14 male), ages between 2 and 10 (mean age 4.62 years), coming from 33 non-related families were evaluated. All cases were diagnosed with severe or profound bilateral congenital SNHL. A statistical comparison of genetic and environmental/clinical prevalence was also attempted since the presence of a genetic disorder cannot rule out the role of other documented risk factors in the etiology of SNHL. The results showed that, 29.4% of cases (10/34) were homozygotic for the 35delG mutation 35delG/35delG), also known as genotype Δ/Δ. 5.88% of cases (2/34) belong to the heterozygotic bi-genic group 35delG/W24X. The clinical factors with high statistical significance for SNHL in a non-genetic group have no significance for genetic SNHL patients. Thus, the present study confirms the relatively high prevalence of the 35delG and W24X mutations in cases of congenital non-syndromic severe of profound bilateral SNHL.

The influence of Slim Modiolar electrode on residual hearing in pediatric patients.

PURPOSE: Hearing preservation cochlear implantation is an established procedure in patients with low-frequency residual hearing, especially in pediatric cochlear implantation. More delicate, thin electrode arrays can minimize damage in the inner ear and enhance the possibility for residual hearing preservation. The Cochlear® CI532 electrode has been reported as an electrode with the potential for residual hearing preservation. No similar studies pertaining to hearing preservation in pediatric patients have appeared to date. The aim of this study was to investigate whether the Cochlear® CI532 Slim Modiolar electrode allows the preservation of low-frequency residual hearing in children undergoing cochlear implantation. METHODS: In this multicenter, nonrandomized, prospective clinical cohort study, medical data of 14 pediatric patients implanted with the CI532 were collected. All patients had residual low-frequency hearing (preoperative audiogram or ABR with at least one threshold better than 90 dB HL at 125, 250, 500, or 1000 Hz). Postoperative thresholds were obtained 1, 3, 6, and 12 months after cochlear implantation. RESULTS: Based on the HEARRING classification, 78.6% of children (11/14) had complete hearing preservation at the last follow-up visit (12 months after CI, or if not available, 6 months). A total of 21.4% (3/14) had partial hearing preservation. At the last follow-up visit, neither minimal hearing preservation nor loss of hearing was observed. Functional low-frequency hearing was preserved in 13 out of 14 patients (93%). CONCLUSIONS: The residual hearing preservation results in children were superior to the results previously reported in adults.

How anxious did you feel during lockdown? The roles resilience, living environment, and gender play on the level of anxiety state during pandemic isolation.

In the unique context of the coronavirus disease 2019 (COVID-19) pandemic, researchers and clinicians alike drew attention to the risks involved by physical and social isolation for mental health. Factors like resilience, gender, urban/rural environment, or preexisting anxiety can impact anxious states produced by home forced isolation. Based on these, we assumed that: i) there are significant differences in the level of anxiety (state) during the pandemic, depending on the living area of the subjects; ii) gender plays a moderating role in the relationship between resilience and anxiety; and iii) anxiety (trait), experiential avoidance, resilience, and family connectedness, determine the level of anxiety (state). The MemoryLab team conducted the present study on 495 subjects (n=411 women, age between 18 and 65). Of these, 350 live in large and medium urban areas, 63 in small urban areas, and 82 in rural areas. As instruments, we used The State-Trait Anxiety Inventory (STAI 2.0), The Acceptance and Action Questionnaire 2 (AAQ-2), The Aggression Questionnaire (AQ), The Family Connectedness Questionnaire, and Connor-Davidson Resilience Scale 10 (CD-RISC-10), as well as the standard division of living areas according to community size. Data collection took place online during the spring peak of the pandemic. According to ANOVA analysis, people living in small urban areas have a higher level of anxiety. The difference is significant compared to those living in large and medium cities and villages. Gender has no moderating role in the relationship between resilience and the anxiety state. Also, experiential avoidance, anxiety (trait), and resilience play a significant role on the level of anxiety (state), measured during social isolation. The results could be an important indicator for understanding psychological mechanisms guiding interventions to support the communities effectively.

Core-Shell and Hollow Particles of Carbon and SiC Prepared from Hydrochar.

The applications of silicon carbide (SiC) include lightweight materials with thermal shock resistance. In this study, core-shell C-SiC particles were synthesized by compacting and rapidly heating a hydrochar from glucose by using strong pulsed currents and infiltration of silicon vapor. Hollow particles of SiC formed on removing the carbon template. In contrast to related studies, we detected not only the pure 3C polytype (ß-SiC) but also significant amounts of the 2H or the 6H polytypes (α-SiC) in the SiC.

Amorphous Calcium Carbonate Constructed from Nanoparticle Aggregates with Unprecedented Surface Area and Mesoporosity.

Amorphous calcium carbonate (ACC), with the highest reported specific surface area of all current forms of calcium carbonate (over 350 m2 g-1), was synthesized using a surfactant-free, one-pot method. Electron microscopy, helium pycnometry, and nitrogen sorption analysis revealed that this highly mesoporous ACC, with a pore volume of ∼0.86 cm3 g-1 and a pore-size distribution centered at 8-9 nm, is constructed from aggregated ACC nanoparticles with an estimated average diameter of 7.3 nm. The porous ACC remained amorphous and retained its high porosity for over 3 weeks under semi-air-tight storage conditions. Powder X-ray diffraction, large-angle X-ray scattering, infrared spectroscopy, and electron diffraction exposed that the porous ACC did not resemble any of the known CaCO3 structures. The atomic order of porous ACC diminished at interatomic distances over 8 Å. Porous ACC was evaluated as a potential drug carrier of poorly soluble substances in vitro. Itraconazole and celecoxib remained stable in their amorphous forms within the pores of the material. Drug release rates were significantly enhanced for both drugs (up to 65 times the dissolution rates for the crystalline forms), and supersaturation release of celecoxib was also demonstrated. Citric acid was used to enhance the stability of the ACC nanoparticles within the aggregates, which increased the surface area of the material to over 600 m2 g-1. This porous ACC has potential for use in various applications where surface area is important, including adsorption, catalysis, medication, and bone regeneration.

Hydride Reduction of BaTiO3 - Oxyhydride Versus O Vacancy Formation.

We investigated the hydride reduction of tetragonal BaTiO3 using the metal hydrides CaH2, NaH, MgH2, NaBH4, and NaAlH4. The reactions employed molar BaTiO3/H ratios of up to 1.8 and temperatures near 600 °C. The air-stable reduced products were characterized by powder X-ray diffraction (PXRD), transmission electron microscopy, thermogravimetric analysis (TGA), and 1H magic angle spinning (MAS) NMR spectroscopy. PXRD showed the formation of cubic products-indicative of the formation of BaTiO3-x H x -except for NaH. Lattice parameters were in a range between 4.005 Å (for NaBH4-reduced samples) and 4.033 Å (for MgH2-reduced samples). With increasing H/BaTiO3 ratio, CaH2-, NaAlH4-, and MgH2-reduced samples were afforded as two-phase mixtures. TGA in air flow showed significant weight increases of up to 3.5% for reduced BaTiO3, suggesting that metal hydride reduction yielded oxyhydrides BaTiO3-x H x with x values larger than 0.5. 1H MAS NMR spectroscopy, however, revealed rather low concentrations of H and thus a simultaneous presence of O vacancies in reduced BaTiO3. It has to be concluded that hydride reduction of BaTiO3 yields complex disordered materials BaTiO3-x H y □(x-y) with x up to 0.6 and y in a range 0.04-0.25, rather than homogeneous solid solutions BaTiO3-x H x . Resonances of (hydridic) H substituting O in the cubic perovskite structure appear in the -2 to -60 ppm spectral region. The large range of negative chemical shifts and breadth of the signals signifies metallic conductivity and structural disorder in BaTiO3-x H y □(x-y). Sintering of BaTiO3-x H y □(x-y) in a gaseous H2 atmosphere resulted in more ordered materials, as indicated by considerably sharper 1H resonances.

Local disorder in Na0.5Bi0.5TiO3-piezoceramic determined by 3D electron diffuse scattering.

Local structural distortions in Na0.5Bi0.5TiO3-based solid solutions have been proved to play a crucial role in understanding and tuning their enhanced piezoelectric properties near the morphotropic phase boundary. In this work all local structural disorders in a lead-free ternary system, namely 85%Na0.5Bi0.5TiO3-10%Bi0.5K0.5TiO3-5%BaTiO3, were mapped in reciprocal space by 3D electron diffraction. Furthermore, a comprehensive model of the local disorder was developed by analysing the intensity and morphology of the observed weak diffuse scattering. We found that the studied ceramics consists of plate-like in-phase oxygen octahedral nanoscale domains randomly distributed in an antiphase tilted matrix. In addition, A-site chemical short-range order of Na/Bi and polar displacements contribute to different kinds of diffuse scattering. The proposed model explains all the observed diffraction features and offers insight into the ongoing controversy over the nature of local structural distortions in Na0.5Bi0.5TiO3-based solid solutions.

Superior Semicircular Canal Ampullae Dehiscence As Part of the Spectrum of the Third Window Abnormalities: A Case Study.

A 60-year-old man was referred to the ENT department for intense episodic vertigo triggered by loud sounds. Pure tone audiometry and otoneurological assessment, including videonystagmography using auditory stimulation and cervical vestibular evoked myogenic potential measures, conducted to the hypothesis of a third window syndrome in the left ear. Results from the high-resolution computed tomography of the petrous bone confirmed the hypothesis and revealed the presence of a submillimeter semicircular canal dehiscence, located between the left lateral and superior semicircular canal ampullae on the left side.

[Synthesis and characterization of some new rutin and 7-aminocephalosporanic acid derivatives]. / Sinteza si caracterizarea unor noi derivati ai rutozidului cu acid 7-amino-cefalosporanic.

UNLABELLED: Many studies show that flavonoids have a numerous biological properties, antimicrobial effects included. It is also known that rutin is able to increase the antibacterial activity of other compounds. MATERIAL AND METHODS: Starting from these facts, we synthesised some water soluble rutin derivatives treating rutin with 1, 3-dichloro-2-propanol, 1-bromo-3-chloro-propane, 2-dibromethane, and dibrommethane, and than with 7-amino-cephalosporanic acid. The antimicrobial activity of the new compounds was determined by disc diffusion method. RESULTS: Molecular formula, weight, yield, melting points and solubility of the new derivatives have been determined. Elemental analysis and spectral analysis (UV and IR) confirmed the structure of new compounds. CONCLUSIONS. These derivatives are water-soluble and have a good antimicrobial activity, both on Gram-positive and Gram-negative bacteria, comparable with that of tetracycline.