Long term behavior of dexamethasone-loaded cochlear implants: In vitro & in vivo.

The aim of this study was to better understand the long term behavior of silicone-based cochlear implants loaded with dexamethasone: in vitro as well as in vivo (gerbils). This type of local controlled drug delivery systems offers an interesting potential for the treatment of hearing loss. Because very long release periods are targeted (several years/decades), product optimization is highly challenging. Up to now, only little is known on the long term behavior of these systems, including their drug release patterns as well as potential swelling or shrinking upon exposure to aqueous media or living tissue. Different types of cylindrical, cochlear implants were prepared by injection molding, varying their dimensions (being suitable for use in humans or gerbils) and initial drug loading (0, 1 or 10%). Dexamethasone release was monitored in vitro upon exposure to artificial perilymph at 37 °C for >3 years. Optical microscopy, X-ray diffraction and Raman imaging were used to characterize the implants before and after exposure to the release medium in vitro, as well as after 2 years implantation in gerbils. Importantly, in all cases dexamethasone release was reliably controlled during the observation periods. Diffusional mass transport and limited drug solubility effects within the silicone matrices seem to play a major role. Initially, the dexamethasone is homogeneously distributed throughout the polymeric matrices in the form of tiny crystals. Upon exposure to aqueous media or living tissue, limited amounts of water penetrate into the implant, dissolve the drug, which subsequently diffuses out. Surface-near regions are depleted first, resulting in an increase in the apparent drug diffusivity with time. No evidence for noteworthy implant swelling or shrinkage was observed in vitro, nor in vivo. A simplified mathematical model can be used to facilitate drug product optimization, allowing the prediction of the resulting drug release rates during decades as a function of the implant's design.

3D analysis of gerbil cochlea with cochlear implant.

OBJECTIVES: To assess a clearing protocol using ethyl cinnamate, an organic substance which is non-toxic for humans, and its value in light-sheet microscopy study of post-implantation cochlear damage in the Mongolian gerbil. MATERIAL AND METHODS: The animals underwent right cochlear implantation in the round window by a retroauricular approach. They were then euthanized 10 weeks after implantation (electrode array in place). The cochleae were prepared according to a 29-day protocol including steps of fixation, microdissection, decalcification, permeabilization, blocking, fluorescent immunolabeling, dehydration and finally clearing in ethyl cinnamate solution. Acquisition of transparent cochleae was performed by light-sheet microscopy. Imaris software was then used for 3D analysis. RESULTS: The transparent cochleae had not undergone any shrinkage or any significant architectural changes. Six cochleae were acquired by light-sheet microscopy, allowing good visibility of the whole cochlea. 3D immunofluorescence analysis of the cochlea provided sufficient image resolution for analysis of the spiral ganglion neurons and assessment of the fibrotic tissue reaction surrounding the electrode array. CONCLUSION: The ethyl cinnamate clearing protocol was effective for light-sheet microscopy analysis of the whole Mongolian gerbil cochlea with the implant left in situ. This technique is suitable for the study of post-implantation cell and tissue damage in the same sample, without the potential toxicity of other methods described to date.

Tolerance of salivary gland botulinum toxin A injection under local anesthesia for the treatment of sialorrhea in children: An observational study.

OBJECTIVES: The main objective of this study was to assess tolerance of botulinum toxin A injection into the salivary glands under local anesthesia in a pediatric population. Secondary endpoints comprised efficacy and side-effects. MATERIAL AND METHODS: A retrospective observational study included children treated between January 2013 and March 2020 for sialorrhea and/or pharyngeal salivary congestion. Children were identified from the botulinum toxin A injection database. The study included 162 injection sessions in 55 children. Injections were performed under local anesthesia with nitrous oxide, after clinical location of the site. Epidemiological and clinical data, injection tolerance on the FLACC scale, treatment response and complications were recorded. RESULTS: For submandibular gland injections, pain was absent in 81 cases, mild in 64, moderate in 4 and intense in 1. In parotid gland injections, pain was absent in 45 cases, mild in 89, moderate in 17 and intense in 1. Injection tolerance was significantly poorer (P<0.005) in parotid than submandibular glands. Seventy-seven percent of the injections had a positive effect on sialorrhea. Fifteen patients presented transient adverse events: mainly dysphagia and paradoxical increase in sialorrhea. CONCLUSION: Salivary gland botulinum toxin A injections in under local anesthesia were well-tolerated, safe and effective for children with sialorrhea and/or pharyngeal salivary congestion.

Interplay of disorder and antiferromagnetism in TlFe(1.6+δ)(Se(1-x)S(x))2 probed by neutron scattering.

The effect of selenium substitution by sulphur on the structural and physical properties of antiferromagnetic TlFe1.6+δSe2 has been investigated via neutron, x-ray and electron diffraction, and transport measurements. The √5a×√5a×c super-cell related to the iron vacancy ordering found in the pure TlFe1.6Se2 selenide is also present in the S-doped TlFe1.6+δ(Se1-xSx)2 compounds. Neutron scattering experiments show the occurrence of the same long range magnetic ordering in the whole series i.e. the 'block checkerboard' antiferromagnetic structure. In particular, this is the first detailed study where the crystal structure and the √5a×√5a antiferromagnetic structure is characterized by neutron powder diffraction for the pure TlFe1.6+δS2 sulphide over a large temperature range. We demonstrate the strong correlation between occupancies of the crystallographic iron sites, the level of iron vacancy ordering and the occurrence of block antiferromagnetism in the sulphur series. Introducing S into the Se sites also increases the Fe content in TlFe1.6+δ(Se1-xSx)2 which in turn leads to the disappearance of the Fe vacancy ordering at x = 0.5 ± 0.15. However, by reducing the nominal Fe content, the same √5a×√5a×c vacancy ordering and antiferromagnetic order can be recovered also in the pure TlFe1.6+δS2 sulphide with a simultaneous reduction in the Néel temperature from 435 K in the selenide TlFe1.75Se2 to 330 K in the sulphide TlFe1.5S2. The magnetic moment remains high at low temperature throughout the full substitution range, which contributes to the absence of superconductivity in these compounds.

Tunnel diode oscillator measurements of the upper critical magnetic field of FeTe(0.5)Se(0.5).

Temperature dependence of the upper critical magnetic field (Hc2) of single crystalline FeTe0.5Se0.5(Tc = 14.5 K) have been determined by tunnel diode oscillator-based measurements in magnetic fields of up to 55 T and temperatures down to 1.6 K. The Werthamer-Helfand-Hohenberg model accounts for the data for magnetic field applied both parallel (H ‖ ab) and perpendicular (H ‖ c) to the iron conducting plane, in line with a single band superconductivity. Whereas Pauli pair breaking is negligible for H ‖ c, Pauli contribution is evidenced for H ‖ ab with Maki parameter α = 1.4, corresponding to Pauli field HP = 79 T. As a result, the Hc2 anisotropy [Formula: see text] which is already rather small at Tc (γ = 1.6) further decreases as the temperature decreases and becomes smaller than 1 at liquid helium temperatures.

Dependence of the structural, transport and magnetic properties of Tl(1-y)Fe(2-z)(Se(1-x)S(x))2 with isovalent substitution of Se by S.

The effect of selenium substitution by sulfur in the Tl(1-y)Fe(2-z)Se(2) antiferromagnet was studied by x-ray and electron diffraction, magnetization and transport measurements. Tl(0.8)Fe(1.5)(Se(1-x)S(x))(2) (nominal composition) solid solution was synthesized in the full x range (0 ≤ x(S) ≤ 1) using the sealed tube technique. No superconductivity was found down to 4.2 K in the series despite the fact that the optimal crystallographic parameters, determined by Rietveld refinements, are reached in the series (i.e. the Fe-(Se, S) interplane height and (Se, S)-Fe-(Se, S) angle for which the critical superconducting transition T(c) is usually maximal in pnictides). A quasi-full Tl site (y ~ 0.05) compared to significant alkaline deficiency (y = 0.2-0.3) in analogous A(1-y)Fe(2-z)Se(2) (A = K, Rb, Cs), and the resulting differences in iron valency, density of states and doping, are suggested as an explanation for this absence of superconductivity. Transmission electron microscopy confirmed the existence of an ordered iron vacancies network in the samples of the Tl(0.8)Fe(1.5)(Se(1-x)S(x))(2) series in the form of the tetragonal √5a × âˆš5a × c superstructure (I4/m). The Néel temperature (T(N)) indicating the onset of antiferromagnetism order in this √5a × âˆš5a × c supercell is found to decrease from 450 K in the selenide (x = 0) to 330 K in the sulfide (x = 1). Finally, we demonstrate a direct linear relationship between T(N) and the Fe-(Se, S) bond length (or Fe-(Se, S) height).

Disorder effects in pnictides: a tunneling spectroscopy study.

We present the synthesis and the tunneling spectroscopy study of superconducting FeSe(0.5)Te(0.5) (T(c) = 14 K), SmFeAsO(0.85) (T(c) = 54 K) and SmFeAsO(0.9)F(0.1) (T(c) = 45 K). The samples were characterized by Rietveld refinement of x-ray diffraction patterns and transport as well as temperature-dependent magnetic measurements. Tunneling experiments on FeSe(0.5)Te(0.5) revealed a single superconducting gap ∼ 1 meV in BCS-like tunneling conductance spectra. In SmFeAsO(0.85) and SmFeAsO(0.9)F(0.1), however, more complex spectra were observed, characterized by two gap-like structures at ∼ 4 and ∼ 10 meV. These spectra are qualitatively understood assuming a two-band superconductor with a 's ±' order parameter. We show that, depending on the sign relation between the pairing amplitudes in the two bands, the interband quasiparticle scattering has a crucial effect on the shape of the tunneling spectra. On the other hand, single-gap spectra found in FeSe(0.5)Te(0.5) are more compatible with a disorder-induced 's '-wave gap, due to the Se-Te substitution.

[Association of disseminated lupus erythematosus and Crohn's disease]. / Association entre un lupus érythémateux disséminé et une maladie de Crohn.

INTRODUCTION: Association of Crohn's disease and systemic lupus erythematosus is infrequent. We report an observation of Crohn's disease that appeared in an 18-year-old woman followed-up for systemic lupus erythematosus for four years. EXEGESIS: The patient had all the clinical, biological and histological criteria of Crohn's disease and systemic lupus erythematosus was diagnosed according to the American Rheumatism Association criteria. On the base of this observation, we discuss the digestive manifestation of systemic lupus erythematosus and extradigestive manifestations of Crohn's disease. CONCLUSION: The immunological background of both diseases was proposed to explain the mechanism of this rare association.

[Congenital cyst of the common hepatic duct. Adenocarcinoma of the gall bladder and of the stomach (author's transl)]. / Kyste congénital du canal hépatique commun. Adénocarcinome vésiculaire et adénocarcinome gastrique.

The authors report an unusual case of coexistence in the same patient of a congenital cyst of the common bile duct, a mucous adenocarcinoma of the stomach and a gall bladder adenocarcinoma. There was a favourable short term course after gastrectomy, cholecystectomy and resection of the cyst followed by bilio-digestive anastomosis on a long jejunal Y-shaped loop. The authors review recent literature.