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1.
Artículo en Inglés | MEDLINE | ID: mdl-38703197

RESUMEN

PURPOSE: Perceived social support has been shown to positively correlate with health-related quality of life (HR-QoL) in a variety of conditions. This study investigated whether perceived social support is affecting HR-QoL of patients who receive a cochlear implant (CI) for deafness. METHODS: Eighty eight adults (56 males, 32 females; mean age: 60 years) with a uni- or bilateral CI for bilateral high-grade hearing loss were administered two questionnaires: a questionnaire for perceived social support (FSU-14) and the Nijmegen Cochlear Implant Questionnaire (NCIQ) for hearing-specific HR-QoL. Administration of the questionnaires occurred at four points in time: before implantation and three, 12 and 24 months after implant activation. RESULTS: The CI patients had quite high levels of perceived social support (mean percentile rank: 71), which remained stable at all four measurement points. Multivariate Analysis showed a significant interaction between perceived social support and HR-QoL indicating that higher perceived social support lead to higher improvement of HR-QoL after cochlear implantation. CONCLUSION: The CI patients in this study had higher than average levels of perceived social support, which did not change before and after cochlear implantation. Perceived social support and HR-QoL were related such that patients with high levels of perceived social support experienced greater improvement of their HR-QoL after cochlear implantation than patients with low levels of perceived social support. Based on this finding, perceived social support must be considered as an important factor for HR-QoL after cochlear implantation.

2.
Cryst Growth Des ; 24(5): 2217-2225, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38463616

RESUMEN

Molecular crystal structures are often interpreted in terms of strong, structure directing, intermolecular interactions, especially those with distinct geometric signatures such as H-bonds or π-stacking interactions. Other interactions can be overlooked, perhaps because they are weak or lack a characteristic geometry. We show that although the cumulative effect of weak interactions is significant, their deformability also leads to occupation of low energy vibrational energy levels, which provides an additional stabilizing entropic contribution. The entropies of five fluorobenzene derivatives have been calculated by periodic DFT calculations to assess the entropic influence of C-H···F interactions in stabilizing their crystal structures. Calculations reproduce inelastic neutron scattering data and experimental entropies from heat capacity measurements. C-H···F contacts are shown to have force constants which are around half of those of more familiar interactions such as hydrogen bonds, halogen bonds, and C-H···π interactions. This feature, in combination with the relatively high mass of F, means that the lowest energy vibrations in crystalline fluorobenzenes are dominated by C-H···F contributions. C-H···F contacts occur much more frequently than would be expected from their enthalpic contributions alone, but at 150 K, the stabilizing contribution of entropy provides, at -10 to -15 kJ mol-1, a similar level of stabilization to the N-H···N hydrogen bond in ammonia and O-H···O hydrogen bond in water.

3.
HNO ; 2024 Feb 29.
Artículo en Alemán | MEDLINE | ID: mdl-38424382

RESUMEN

BACKGROUND: The Nijmegen Cochlear Implant Questionnaire (NCIQ) is a questionnaire for assessing hearing-specific quality of life in the context of cochlear implantation. Its length (60 items) makes it difficult to use in clinical practice, so a short version is desirable. The question arises as to which items should be selected for the short version. METHODS: The items were selected statistically using uncorrected item-total score correlation. Item selection was made based on datasets from three measurement points: before implantation and 3 and 12 months after processor activation. The items were selected according to the criterion that they were among the 40 items with the highest item-total score correlation at each of the three measurement points. RESULTS: Of the 60 items in the NCIQ, 25 met the criterion and were hence included in the short version. The short version yields similar scores as the long version at the postoperative timepoints; however, at the preoperative timepoint, the agreement of the scores is suboptimal. Split-half reliability and internal homogeneity of the short version are very good. CONCLUSION: The present study constitutes an initial positive evaluation of a short form of the NCIQ in terms of standard psychometric criteria. Application of the short form is associated with significantly reduced resources in terms of processing and evaluating.

4.
J Am Chem Soc ; 145(50): 27367-27379, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38060428

RESUMEN

Despite their hydrophobic surfaces with localized π-holes and rigid well-defined architectures providing a scaffold for preorganizing binding motifs, fullerenes remain unexplored as potential supramolecular host platforms for the recognition of anions. Herein, we present the first example of the rational design, synthesis, and unique recognition properties of novel fullerene-functionalized halogen-bonding (XB) heteroditopic ion-pair receptors containing cation and anion binding domains spatially separated by C60. Fullerene spatial separation of the XB donors and the crown ether complexed potassium cation resulted in a rare example of an artificial receptor containing two anion binding sites with opposing preferences for hard and soft halides. Importantly, the incorporation of the C60 motif into the heteroditopic receptor structure has a significant effect on the halide binding selectivity, which is further amplified upon K+ cation binding. The potassium cation complexed fullerene-based receptors exhibit enhanced selectivity for the soft polarizable iodide ion which is assisted by the C60 scaffold preorganizing the potent XB-based binding domains, anion-π interactions, and the exceptional polarizability of the fullerene moiety, as evidenced from DFT calculations. These observations serve to highlight the unique properties of fullerene surfaces for proximal charged guest binding with potential applications in construction of selective molecular sensors and modulating the properties of solar cell devices.

5.
Orphanet J Rare Dis ; 18(1): 219, 2023 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-37501185

RESUMEN

Foramen magnum stenosis is a serious, and potentially life-threatening complication of achondroplasia. The foramen magnum is smaller in infants with achondroplasia, compared with the general population, and both restricted growth in the first 2 years and premature closure of skull plate synchondroses can contribute to narrowing. Narrowing of the foramen magnum can lead to compression of the brainstem and spinal cord, and result in sleep apnoea and sudden death. There is a lack of clarity in the literature on the timing of regular monitoring for foramen magnum stenosis, which assessments should be carried out and when regular screening should be ceased. The European Achondroplasia Forum (EAF) is a group of clinicians and patient advocates, representative of the achondroplasia community. Members of the EAF Steering Committee were invited to submit suggestions for guiding principles for the detection and management of foramen magnum stenosis, which were collated and discussed at an open workshop. Each principle was scrutinised for content and wording, and anonymous voting held to pass the principle and vote on the level of agreement. A total of six guiding principles were developed which incorporate routine clinical monitoring of infants and young children, timing of routine MRI screening, referral of suspected foramen magnum stenosis to a neurosurgeon, the combination of assessments to inform the decision to decompress the foramen magnum, joint decision making to proceed with decompression, and management of older children in whom previously undetected foramen magnum stenosis is identified. All principles achieved the ≥ 75% majority needed to pass (range 89-100%), with high levels of agreement (range 7.6-8.9). By developing guiding principles for the detection and management of foramen magnum stenosis, the EAF aim to enable infants and young children to receive optimal monitoring for this potentially life-threatening complication.


Asunto(s)
Acondroplasia , Enfermedades Óseas , Síndromes de la Apnea del Sueño , Niño , Lactante , Humanos , Adolescente , Preescolar , Foramen Magno/cirugía , Constricción Patológica/diagnóstico , Constricción Patológica/complicaciones , Acondroplasia/diagnóstico , Acondroplasia/terapia , Acondroplasia/complicaciones , Síndromes de la Apnea del Sueño/diagnóstico , Médula Espinal , Enfermedades Óseas/complicaciones
6.
J Clin Endocrinol Metab ; 108(11): e1199-e1204, 2023 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-37256841

RESUMEN

CONTEXT: Treatment of children with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is challenging. Linear growth and adult height are compromised according to recent publications. However, most of these data were obtained in the era before CAH newborn screening. DESIGN: Body height of patients with classical CAH diagnosed before and after the establishment of newborn screening were analyzed retrospectively. PATIENTS AND METHODS: We identified 600 patients with classical CAH (227 male) with data on near-adult height (NAH), target height (TH), and information on newborn screening from the electronic German CAH registry (German Society for Paediatric Endocrinology and Diabetology). Newborn screening was performed in 101 (16.8%) patients. All patients received hydrocortisone with or without fludrocortisone.To assess the effects of newborn screening, a linear regression model adjusted/stratified for sex and phenotype was used (SAS 9.4). RESULTS: TH corrected NAH (mean; 95% confidence interval) was closer to 0 in patients with CAH and newborn screening [-0.25 standard deviation score (SDS); -0.44 to -0.06] than in patients without newborn screening (-0.44 SDS; -0.52 to -0.36) (P = .069). Screening had no effect on NAH in female patients. In male patients, NAH was significantly better (P = .033) with screening than without screening. After stratifying for CAH phenotype, screening did not affect the NAH of patients with salt-wasting CAH. Patients with simple-virilizing CAH had a significantly better cNAH (P = .034) with screening (0.15 SDS; -0.28-0.59) than without screening (-0.35 SDS; -0.52 to -0.18). CONCLUSIONS: Our data suggest that newborn screening might be associated with improved NAH in male CAH patients and in patients with simple-virilizing CAH.


Asunto(s)
Hiperplasia Suprarrenal Congénita , Niño , Recién Nacido , Humanos , Masculino , Femenino , Adulto , Hiperplasia Suprarrenal Congénita/diagnóstico , Estudios Retrospectivos , Tamizaje Neonatal , Hidrocortisona/farmacología , Glucocorticoides/farmacología , Estatura
7.
J Am Chem Soc ; 145(4): 2661-2668, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36652378

RESUMEN

Synthetic supramolecular transmembrane anionophores have emerged as promising anticancer chemotherapeutics. However, key to their targeted application is achieving spatiotemporally controlled activity. Herein, we report a series of chalcogen-bonding diaryl tellurium-based transporters in which their anion binding potency and anionophoric activity are controlled through reversible redox cycling between Te oxidation states. This unprecedented in situ reversible multistate switching allows for switching between ON and OFF anion transport and is crucially achieved with biomimetic chemical redox couples.

8.
Angew Chem Int Ed Engl ; 62(5): e202214785, 2023 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-36440816

RESUMEN

The first examples of halogen bonding (XB) heteroditopic homo[2]catenanes were prepared by discrete Na+ template-directed assembly of oligo(ethylene glycol) units derived from XB donor-containing macrocycles and acyclic bis-azide precursors, followed by a CuI -mediated azide-alkyne cycloaddition macrocyclisation reaction. Extensive 1 H NMR spectroscopic studies show the [2]catenane hosts exhibit positive cooperative ion-pair recognition behaviour, wherein XB-mediated halide recognition is enhanced by alkali metal cation pre-complexation. Notably, subtle changes in the catenanes' oligo(ethylene glycol) chain length dramatically alters their ion-binding affinity, stoichiometry, complexation mode, and conformational dynamics. Solution-phase and single-crystal X-ray diffraction studies provide evidence for competing host-separated and direct-contact ion-pair binding modes. We further demonstrate the [2]catenanes are capable of extracting solid alkali-metal halide salts into organic media.

9.
Ear Hear ; 44(2): 264-275, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36163636

RESUMEN

OBJECTIVES: Intelligence as a construct of cognitive abilities is the basis of knowledge and skill acquisition and the main predictor of academic achievement. As a broad construct, it is usually divided into subdomains, such as nonverbal and verbal intelligence. Verbal intelligence is one domain of intelligence but is not synonymous with specific linguistic abilities like grammar proficiency. We aim to address the general expectation that early cochlear implantation enables children who are hard of hearing to develop comprehensively, including with respect to verbal intelligence. The primary purpose of this study is to trace the longitudinal development of verbal and nonverbal intelligence in children with cochlear implants (CIs). DESIGN: Sixteen children with congenital hearing loss who received unilateral or bilateral implants and completed at least two intelligence assessments around the age of school entrance were included in the study. The first assessment was performed around 3 years after CI fitting (chronological age range: 3.93 to 7.03 years). The second assessment was performed approximately 2 years after the first assessment. To analyze verbal and nonverbal IQ in conjunction and across children at different ages, we used corresponding standardized and normalized tests from the same test family (Wechsler Preschool and Primary Scale of Intelligence and/or Wechsler Intelligence Scale for Children). RESULTS: Regarding longitudinal development, both verbal and nonverbal IQ increased, but verbal IQ increased more substantially over time. At the time of the second measurement, verbal and nonverbal IQ were on a comparable level. Nevertheless, we also observed strong inter-individual differences. The duration between both assessments was significantly associated with verbal IQ at the second measurement time point and thus with verbal IQ gain over time. Education mode (regular vs. special kindergarten/school) was significantly correlated with nonverbal IQ at the second assessment time point. CONCLUSIONS: The results, despite the small sample size, clearly suggest that children with CIs can achieve intellectual abilities comparable to those of their normal-hearing peers by around the third year after initial CI fitting, and they continue to improve over the following 2 years. We recommend further research focusing on verbal IQ assessed around the age of school entrance to be used as a predictor for further development and for the establishment of an individual educational program.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Sordera , Preescolar , Humanos , Niño , Inteligencia , Sordera/cirugía , Pruebas de Inteligencia
10.
Chemistry ; 28(67): e202201838, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-35968660

RESUMEN

The synthesis and characterisation of a library of acyclic antimony(III) and bismuth(III) triaryl pnictogen bonding (PnB) receptor systems are reported. In the first-generation receptor series, quantitative 1 H NMR chloride titration experiments in THF solvent media reveal halide anion binding potency is intimately correlated with both the electronic-withdrawing nature of the aryl- substituent and the polarisability of the PnB donor. Further extensive anion binding investigations with the most potent Sb- and Bi-based PnB receptors: 1⋅Sb2CF3 and 1⋅Bi2CF3 , reveal novel selectivity profiles, both displaying Cl- selectivity relative to the heavier halides and, impressively, to a range of highly basic oxoanions. The synthesis and preliminary chloride anion binding studies of a series of novel tripodal tris-proto-triazole triaryl Sb(III) and Bi(III) mixed PnB-HB receptor systems are also described. Whereas parent triphenyl Sb(III) and Bi(III) compounds are incapable of binding Cl- in THF solvent media, the PnB-triazole HB host systems exhibit notable halide affinity.


Asunto(s)
Antimonio , Bismuto , Antimonio/química , Bismuto/química , Cloruros , Aniones/química , Halógenos/química , Triazoles/química , Solventes
11.
J Am Chem Soc ; 144(32): 14778-14789, 2022 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-35930460

RESUMEN

Chalcogen bonding (ChB) is rapidly rising to prominence in supramolecular chemistry as a powerful sigma (σ)-hole-based noncovalent interaction, especially for applications in the field of molecular recognition. Recent studies have demonstrated ChB donor strength and potency to be remarkably sensitive to local electronic environments, including redox-switchable on/off anion binding and sensing capability. Influencing the unique electronic and geometric environment sensitivity of ChB interactions through simultaneous cobound metal cation recognition, herein, we present the first potassium chloride-selective heteroditopic ion-pair receptor. The direct conjugation of benzo-15-crown-5 ether (B15C5) appendages to Te centers in a bis-tellurotriazole framework facilitates alkali metal halide (MX) ion-pair binding through the formation of a cofacial intramolecular bis-B15C5 M+ (M+ = K+, Rb+, Cs+) sandwich complex and bidentate ChB···X- formation. Extensive quantitative 1H NMR ion-pair affinity titration experiments, solid-liquid and liquid-liquid extraction, and U-tube transport studies all demonstrate unprecedented KCl selectivity over all other group 1 metal chlorides. It is demonstrated that the origin of the receptor's ion-pair binding cooperativity and KCl selectivity arises from an electronic polarization of the ChB donors induced by the cobound alkali metal cation. Importantly, the magnitude of this switch on Te-centered electrophilicity, and therefore anion-binding affinity, is shown to correlate with the inherent Lewis acidity of the alkali metal cation. Extensive computational DFT investigations corroborated the experimental alkali metal cation-anion ion-pair binding observations for halides and oxoanions.


Asunto(s)
Calcógenos , Metales Alcalinos , Aniones/química , Cationes/química , Cloruros , Cloruro de Potasio
12.
Chem Commun (Camb) ; 58(20): 3318-3321, 2022 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-35179155

RESUMEN

The synthesis and characterisation of two novel molecular organotelluroxane clusters, comprising of an inorganic Te8O6X4 (X = Cl, Br) core structure are described. The integration of highly electron withdrawing 3,5-bis-trifluoromethylphenyl groups to the constituent Te(IV) centres is determined to be crucial in the chalcogen bonding (ChB) halide template directed assembly. Characterised by multi-nuclear 1H, 125Te, 19F NMR, UV-Vis, IR spectroscopies and X-ray crystal structure analysis, the discrete molecular clusters exhibit excellent organic solvent solubility and remarkable chemical stability. Furthermore, preliminary fluorescence investigations reveal the telluroxanes exhibit aggregation induced emission (AIE) behaviour in organic aqueous solvent mixtures.

13.
Angew Chem Int Ed Engl ; 60(40): 21973-21978, 2021 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-34297867

RESUMEN

A series of acyclic anion receptors containing chalcogen bond (ChB) and halogen bond (XB) donors integrated into a neutral 3,5-bis-triazole pyridine scaffold are described, in which systematic variation of the electronic-withdrawing nature of the aryl substituents reveal a dramatic modulation in sigma-hole donor atom potency for anion recognition. Incorporation of strongly electron-withdrawing perfluorophenyl units appended to the triazole heterocycle telluro- or iodo- donor atoms, or directly linked to the tellurium donor atom dramatically enhances the anion binding potency of the sigma-hole receptors, most notably for the ChB and XB receptors displaying over thirty-fold and eight-fold increase in chloride anion affinity, respectively, relative to unfluorinated analogues. Linear free energy relationships for a series of ChB based receptors reveal the halide anion recognition behaviour of the tellurium donor is highly sensitive to local electronic environments. This is especially the case for those directly appended to the Te centre (3⋅ChB), where a remarkable enhancement of strength of binding and selectivity for the lighter halides is observed as the electron-withdrawing ability of the Te-bonded aryl group increases, highlighting the exciting opportunity to fine-tune anion affinity and selectivity in ChB-based receptor systems.

14.
Angew Chem Int Ed Engl ; 60(35): 19442-19450, 2021 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-34185375

RESUMEN

A series of tetraphenylethene (TPE) derivatives functionalized with highly potent electron-deficient perfluoroaryl iodo-triazole halogen bond (XB) donors for anion recognition are reported. 1 H NMR titration experiments, fluorescence spectroscopy, dynamic light scattering measurements, TEM imaging and X-ray crystal structure analysis reveal that the tetra-substituted halogen bonding receptor forms luminescent nanoscale aggregates, the formation of which is driven by XB-mediated anion coordination. This anion-coordination-induced aggregation effect serves as a powerful sensory mechanism, capable of luminescence chloride sensing at parts per billion concentration. Furthermore, the doubly substituted geometric isomers act as unprecedented photoswitchable XB donor anion receptors, where the composition of the photostationary state can be modulated by the presence of a coordinating halide anion.

15.
Chemistry ; 27(45): 11738-11745, 2021 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-34014001

RESUMEN

Synthetic anion transporters show much promise as potential anti-cancer agents and therapeutics for diseases associated with mis-regulation of protein anion channels. In such applications high activity and anion selectivity are crucial to overcome competing proton or hydroxide transport which dissipates cellular pH gradients. Here, highly active bidentate halogen bonding and chalcogen bonding anion carriers based on electron deficient iodo- and telluromethyl-triazole derivatives are reported. Anion transport experiments in lipid bilayer vesicles reveal record nanomolar chloride transport activity for the bidentate halogen bonding anion carrier, and remarkably high chloride over proton/hydroxide selectivity for the chalcogen bonding anionophore. Computational studies provide further insight into the role of sigma-hole mediated anion recognition and desolvation at the membrane interface. Comparison with hydrogen bonding analogues demonstrates the importance of employing sigma-hole donor motifs in synthetic anionophores for achieving both high transport activity and selectivity.


Asunto(s)
Calcógenos , Halógenos , Aniones , Cloruros , Humanos , Enlace de Hidrógeno
16.
Endocr Connect ; 10(5): 561-569, 2021 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-33909597

RESUMEN

OBJECTIVE: Treatment of classic congenital adrenal hyperplasia (CAH) is necessary to compensate for glucocorticoid/mineralocorticoid deficiencies and to suppress androgen excess. Hydrocortisone (HC) is preferred in growing children with classic CAH but recommendations regarding dosage/administration are inconsistent. The aim of this study was to evaluate HC dosing in children with CAH in relation to chronological age, sex, and phenotype based on a multicenter CAH registry. DESIGN: The CAH registry was initiated in 1997 by the AQUAPE in Germany. On December 31st 2018, data from 1571 patients were included. METHODS: A custom-made electronic health record software is used at the participating centers. Pseudonymized data are transferred for central analysis. Parameters were selected based on current guidelines. Descriptive analyses and linear regression models were implemented with SAS 9.4. RESULTS: We identified 1288 patients on exclusive treatment with hydrocortisone three times daily (604 boys; median age 7.2 years; 817 salt-wasting phenotype, 471 simple-virilizing phenotype). The mean (lower-upper quartiles) daily HC dose (mg/m² body surface area) was 19.4 (18.9-19.8) for patients <3 months (n = 329), 15.0 (14.6-15.3) for age ≥3-12 months (n = 463), 14.0 (13.7-14.3) for age 1-5.9 years (n = 745), 14.2 (14.0-14.5) for age 6 years to puberty entry (n = 669), and 14.9 (14.6-15.2) during puberty to 18 years (n = 801). Fludrocortisone was administered in 74.1% of patients with a median daily dosage of 88.8 µg. CONCLUSION: Our analyses showed that still a high proportion of children are treated with HC doses higher than recommended. This evaluation provides comprehensive information on nationwide hydrocortisone substitution dosages in children with CAH underlining the benefit of systematic data within a registry to assess daily practice.

17.
Otol Neurotol ; 42(6): 799-805, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-33625194

RESUMEN

BACKGROUND: Single-sided deafness (SSD) is associated with a loss of binaural hearing. Major limitations of such patients are poor speech understanding in noisy environments and a lack of spatial hearing. To date, cochlear implantation is the most promising approach to overcome these deficits in this group of patients. OBJECTIVE: Cost-effectiveness analyses of cochlear implantation in patients with unilateral deafness. The model targets Austrian and German SSD patients who can either opt for treatment with a cochlear implant (CI) or decide against a CI and stay without any treatment. METHODS: A Markov model analyzed as microsimulation was developed using TreeAge Pro 2019 software. Pre- and postoperative utility values generated with HUI-3 were used to populate the model. Costs covered by the national insurance were considered. Costs and utilities were discounted by 3%. A model time horizon of 20 years was set. RESULTS: According to Austrian base-case analysis, the incremental cost-utility ratio (ICUR) was €34845.2 per quality-adjusted life year gained when comparing the "CI strategy" to the "no treatment strategy." The ICUR is marginally lower when adapting a German cost perspective-it was €31601.25 per quality-adjusted life year gained. Sensitivity analyses showed that the cost-effectiveness results are stable. Analyses also showed that the longer the time horizon is set, the more favorable the cost-effectiveness result is. CONCLUSIONS: Based on currently available data, the Markov microsimulation model suggests that cochlear implantation is cost-effective in Austrian and German patients with SSD if no other treatment option is considered within the model.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Sordera , Pérdida Auditiva Unilateral , Percepción del Habla , Adulto , Austria , Análisis Costo-Beneficio , Sordera/cirugía , Pérdida Auditiva Unilateral/cirugía , Humanos , Resultado del Tratamiento
18.
Otol Neurotol ; 42(6): 824-831, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-33591069

RESUMEN

OBJECTIVE: To investigate the benefit of bilateral cochlear implantation in adults, who had been implanted being a child under the age of 10 years. STUDY DESIGN: Retrospective data analysis. SETTING: Tertiary referral center with a large cochlear implant program. MAIN OUTCOME MEASURES: Speech understanding in the Freiburg monosyllabic words in quiet and the HSM sentence test in quiet and in background noise. PATIENTS: Seventy-seven bilaterally cochlear implantation implanted adults. RESULTS: Bilateral cochlear implantation in children under the age of 10 years results in a significant benefit in speech comprehension in adulthood. In addition, a dependency regarding the time between the implantations and speech intelligibility was found. CONCLUSION: The results emphasize the benefit of bilateral cochlear implantation with a short interval between the operations in young children not only during formative years but also in adulthood.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Percepción del Habla , Adulto , Niño , Preescolar , Humanos , Estudios Retrospectivos , Resultado del Tratamiento
19.
Am J Hum Genet ; 107(5): 989-999, 2020 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-33053334

RESUMEN

Osteogenesis imperfecta (OI) is characterized primarily by susceptibility to fractures with or without bone deformation. OI is genetically heterogeneous: over 20 genetic causes are recognized. We identified bi-allelic pathogenic KDELR2 variants as a cause of OI in four families. KDELR2 encodes KDEL endoplasmic reticulum protein retention receptor 2, which recycles ER-resident proteins with a KDEL-like peptide from the cis-Golgi to the ER through COPI retrograde transport. Analysis of patient primary fibroblasts showed intracellular decrease of HSP47 and FKBP65 along with reduced procollagen type I in culture media. Electron microscopy identified an abnormal quality of secreted collagen fibrils with increased amount of HSP47 bound to monomeric and multimeric collagen molecules. Mapping the identified KDELR2 variants onto the crystal structure of G. gallus KDELR2 indicated that these lead to an inactive receptor resulting in impaired KDELR2-mediated Golgi-ER transport. Therefore, in KDELR2-deficient individuals, OI most likely occurs because of the inability of HSP47 to bind KDELR2 and dissociate from collagen type I. Instead, HSP47 remains bound to collagen molecules extracellularly, disrupting fiber formation. This highlights the importance of intracellular recycling of ER-resident molecular chaperones for collagen type I and bone metabolism and a crucial role of HSP47 in the KDELR2-associated pathogenic mechanism leading to OI.


Asunto(s)
Huesos/metabolismo , Colágeno Tipo I/metabolismo , Proteínas del Choque Térmico HSP47/metabolismo , Osteogénesis Imperfecta/genética , Proteínas de Transporte Vesicular/metabolismo , Adulto , Alelos , Secuencia de Aminoácidos , Animales , Sitios de Unión , Huesos/patología , Pollos , Preescolar , Colágeno Tipo I/química , Colágeno Tipo I/genética , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/patología , Femenino , Fibroblastos/metabolismo , Fibroblastos/patología , Expresión Génica , Aparato de Golgi/metabolismo , Aparato de Golgi/patología , Proteínas del Choque Térmico HSP47/química , Proteínas del Choque Térmico HSP47/genética , Humanos , Lactante , Masculino , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/metabolismo , Osteogénesis Imperfecta/patología , Linaje , Cultivo Primario de Células , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Estructura Secundaria de Proteína , Transporte de Proteínas , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Proteínas de Transporte Vesicular/química , Proteínas de Transporte Vesicular/genética
20.
Int J Pediatr Otorhinolaryngol ; 138: 110266, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32866797

RESUMEN

INTRODUCTION: To evaluate the safety in cochlear implantation without preoperative computed tomography diagnostics, which was implemented into the protocol of cochlear implantation in 2013, since in the year before, new evidence concerning the risks of ionizing radiation especially in children arose. METHODS: In this retrospective data analysis 89 children under 36 months, which were cochlear implanted from 2008 until 2018 at a tertiary referral centre with a large cochlear implant program were analysed. Fortyfour of the children were implanted before the date of change in 2013 and 45 in the following years up to now. The data about the operative procedures, the postoperative care and the complication rate before and after implementation of the new protocol were compared. RESULTS: Before the date of change in 2013, 100% of patients received preoperative CT diagnostics, in the following years 13.3%. No difference in the duration of surgery, the procedure related and the late complications between the two groups was identified. CONCLUSION: Cochlear implantation in very young children under the age of 36 months without preoperative radiological diagnostics by CT scan of the temporal bone is a safe procedure without additional risks for the patients.


Asunto(s)
Implantación Coclear/métodos , Complicaciones Posoperatorias/etiología , Tomografía Computarizada por Rayos X , Preescolar , Implantación Coclear/efectos adversos , Estudio Históricamente Controlado , Humanos , Lactante , Tempo Operativo , Cuidados Posoperatorios , Periodo Preoperatorio , Estudios Retrospectivos
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