[Surgical management of strabismus in dysthyroid orbitopathy: A retrospective single-center study of 32 cases]. / Prise en charge chirurgicale des strabismes compliquant une orbitopathie dysthyroïdienne : étude rétrospective monocentrique d'une série de 32 cas.

INTRODUCTION: Thyroid-related immune orbitopathy often results in a restrictive strabismus. We report our experience of surgical management in these cases. PATIENTS AND METHODS: We present a retrospective case series conducted on 32 patients, operated between 2008 and 2017. Strabismus surgery was proposed in the postinflammatory stage with stable clinical findings for at least 6 months. It was performed under general anesthesia by recessions of restrictive muscles using a fixed suture technique. Outcomes were graded as excellent, good or poor, according to the presence or absence of diplopia in primary or reading positions, and according to whether prism prescription was necessary. RESULTS: The study included 32 patients (21 women, 11 men) with a mean age of 53 years. Average follow-up was 9.6 months. Eight patients developed diplopia after orbital decompression. Fifteen patients had vertical surgery, 8 horizontal surgery, 9 mixed surgery. A mean of 1.31 surgeries (range 1-3) were performed. After all surgeries, 28 patients (87.5 %) had an excellent outcome, 4 (12.5 %) had a good outcome, and none had a poor outcome. There was a significant improvement in stereoscopic acuity (P<0.01), but not motility. Among the 8 patients who developed diplopia after orbital decompression, a clinically acceptable final outcome was achieved after only one surgery. CONCLUSION: Strabismus surgery using conventional non-adjustable sutures provides excellent ocular alignment and relief from diplopia in the majority of patients with dysthyroid strabismus. The reoperation rate is similar to other techniques, such adjustable suture and intraoperative relaxed muscle technique.

Source analysis of short and long latency vestibular-evoked potentials (VsEPs) produced by left vs. right ear air-conducted 500 Hz tone pips.

Todd et al. (2014) have recently demonstrated the presence of vestibular dependent changes both in the morphology and in the intensity dependence of auditory evoked potentials (AEPs) when passing through the vestibular threshold as determined by vestibular evoked myogenic potentials (VEMPs). In this paper we extend this work by comparing left vs. right ear stimulation and by conducting a source analysis of the resulting evoked potentials of short and long latency. Ten healthy, right-handed subjects were recruited and evoked potentials were recorded to both left- and right-ear sound stimulation, above and below vestibular threshold. Below VEMP threshold, typical AEPs were recorded, consisting of mid-latency (MLR) waves Na and Pa followed by long latency AEPs (LAEPs) N1 and P2. In the supra-threshold condition, the expected changes in morphology were observed, consisting of: (1) short-latency vestibular evoked potentials (VsEPs) which have no auditory correlate, i.e. the ocular VEMP (OVEMP) and inion response related potentials; (2) a later deflection, labelled N42/P52, followed by the LAEPs N1 and P2. Statistical analysis of the vestibular dependent responses indicated a contralateral effect for inion related short-latency responses and a left-ear/right-hemisphere advantage for the long-latency responses. Source analysis indicated that the short-latency effects may be mediated by a contralateral projection to left cerebellum, while the long-latency effects were mediated by a contralateral projection to right cingulate cortex. In addition we found evidence of a possible vestibular contribution to the auditory T-complex in radial temporal lobe sources. These last results raise the possibility that acoustic activation of the otolith organs could potentially contribute to auditory processing.

Is there a relationship between odors and motion sickness?

The aim of this study was to evaluate the relationship between olfaction and motion sickness. A sample of 18 participants was recruited and submitted to three sessions of nauseogenic stimulations: off vertical axis rotation (OVAR), performed under conditions of olfactory stimulation with limonene (pleasant odor), petrol (unpleasant odor) or distilled water (as a control). Motion sickness was assessed before, during and after each OVAR session. In addition, participants were asked to evaluate the intensity and hedonic valence of four odors (geraniol, limonene, butanol, petrol) as well as distilled water (as a control) before and after each OVAR session. Our analysis showed that OVAR has consistently increased the induced-motion sickness. However the addition of an odor that is pleasant or unpleasant during the rotation did not affect the occurrence of motion sickness symptoms compared to the control condition. Our results also showed that intensity of odors was significantly increased after OVAR and the intensity was significantly higher for unpleasant odors than for pleasant one. For the hedonicity, OVAR made unpleasant odors more unpleasant (p<0.0001) while it made limonene odor slightly more pleasant (p<0.05). The present study highlighted the lack of influence of odors in motion-induced sickness but an impact of a nauseogenic test on olfactory perception.

Otolith signals contribute to inter-individual differences in the perception of gravity-centered space.

The aim of the present study was to investigate (1) the relative contribution of the egocentric reference as well as body orientation perception to visual horizon percept during tilt or during increased gravito-inertial acceleration (GiA, hypergravity environment) conditions and (2) the role of vestibular signals in the inter-individual differences observed in these perceptual modalities. Perceptual estimates analysis showed that backward tilt induced (1) an elevation of the visual horizon, (2) an elevation of the egocentric estimation (visual straight ahead) and (3) an overestimation of body tilt. The increase in the magnitude of GiA induced (1) a lowering of the apparent horizon, (2) a lowering of the straight ahead and (3) a perception of backward tilt. Overall, visual horizon percept can be expressed as the combination of body orientation perception and egocentric estimation. When assessing otolith reactivity using off-vertical axis rotation (OVAR), only visual egocentric estimation was significantly correlated with horizontal OVAR performance. On the one hand, we found a correlation between a low modulation amplitude of the otolith responses and straight ahead accuracy when the head axis was tilted relative to gravity. On the other hand, the bias of otolith responses was significantly correlated with straight ahead accuracy when subjects were submitted to an increase in the GiA. Thus, straight ahead sense would be dependent to some extent to otolith function. These results are discussed in terms of the contribution of otolith inputs in the overall multimodal integration subtending spatial constancy.

Motion sickness susceptibility in healthy subjects and vestibular patients: effects of gender, age and trait-anxiety.

Several studies have suggested that anxiety may play a role in motion sickness susceptibility (MSS) variability. This study aimed to assess motion sickness susceptibility in healthy subjects and chronic vestibular patients and to investigate its relationship to gender, age and trait-anxiety. Healthy subjects (n=167) and chronic dizzy patients with various vestibulopathies (n=94), aged from 20 to 92 years old, were asked to complete Motion Sickness Susceptibility questionnaire (MSSQ) and trait-anxiety questionnaire (STAI-B). When patients were divided into those who had vestibular loss (n=51) vs. patients without vestibular loss (n=43), the MSSQ scores (mean ± SD) for patients with vestibular loss (18.8 ± 30.9) were lower than healthy subjects (36.4 ± 34.8), who were lower than vestibular patients without vestibular loss (59.0 ± 39.7). These significant differences could not be explained by gender, age, trait-anxiety, or interaction. Women had higher MSS than men, and MSS declined with age for healthy subjects and vestibular patients. The overall relationship between anxiety and MSS scores was weak and only reached significance in healthy subjects. These results support the conclusion that the vestibular system is heavily involved in MSS and that trait-anxiety may play a role in MSS but only in healthy subjects.

Smart nanocarriers for pH-triggered targeting and release of hydrophobic drugs.

The use of hybrid pH-sensitive micelles based mainly on the (PEO)(129)(P2VP)(43)(PCL)(17) ABC miktoarm star copolymer as potential triggered drug delivery systems was investigated. Co-micellization of this star copolymer with a second copolymer labeled by a targeting ligand, i.e. biotin, on the pH sensitive block (poly-2-vinylpyridine) is considered here in order to impart possible active targeting of the tumor cells. Two architectures were studied for these labeled copolymers, i.e. a miktoarm star or a linear ABC terpolymer, and the respective hybrid micelles are compared in terms of cytotoxicity (cells viability) and cellular uptake (using fluorescent dye loaded micelles). Finally, the triggered drug release in the cytosol of tumor cells was investigated by studying, on the one hand, the lysosomal integrity after internalization and, on the other hand, the release profile in function of the pH.

A pharmaceutical study of doxorubicin-loaded PEGylated nanoparticles for magnetic drug targeting.

One of the new strategies to improve cancer chemotherapy is based on new drug delivery systems, like the polyethylene glycol-coated superparamagnetic iron oxide nanoparticles (PEG-SPION, thereafter called PS). In this study, PS are loaded with doxorubicin (DOX) anticancer drug, using a pre-formed DOX-Fe(2+) complex reversible at lower pH of tumour tissues and cancer cells. The DOX loaded PS (DLPS, 3% w/w DOX/iron oxide) present a hydrodynamic size around 60nm and a zeta potential near zero at physiological pH, both parameters being favourable for increased colloidal stability in biological media and decreased elimination by the immune system. At physiological pH of 7.4, 60% of the loaded drug is gradually released from the DLPS in ∼2h. The intracellular release and distribution of DOX is followed by means of confocal spectral imaging (CSI) of the drug fluorescence. The in vitro cytotoxicity of the DLPS on MCF-7 breast cancer cells is equivalent to that of a DOX solution. The reversible association of DOX to the SPION surface and the role of polymer coating on the drug loading/release are discussed, both being critical for the design of novel stealth magnetic nanovectors for chemotherapy.

Mitochondrial targeting by use of lipid nanocapsules loaded with SV30, an analogue of the small-molecule Bcl-2 inhibitor HA14-1.

Taking advantage from the development of SV30, a new analogue of the pro-apoptotic molecule HA14-1, the aim of this study was to functionally evaluate SV30 and to develop safe nanocarriers for its administration. By using an inversion phase process, 57nm organic solvent-free lipid nanocapsules loaded with SV30 (SV30-LNCs) were formulated. Biological performance of SV30 and SV30-LNCs were evaluated on F98 cells that express Bax and Bcl-2, through survival assays, HPLC, flow cytometry, confocal microscopy and spectral imaging. We observed that SV30 alone or in combination with paclitaxel, etoposide or beam radiation could trigger cell death in a similar fashion to HA14-1. Although partially blocked by Z-VAD-fmk, this effect was coincident to caspase-3 activation. Hence, we established that SV30-LNCs improved SV30 biological activity together with a potentiation of the mitochondrial membrane potential decrease. Interestingly, flow cytometry and confocal analysis indicated that SV30 itself conferred to LNCs improved mitochondrial targeting skills that may present a great interest toward the development of mitochondria targeted nanomedicines.

Influence of multisensory graviceptive information on the apparent zenith.

We studied the contribution of vestibular and somatosensory/proprioceptive stimulation to the perception of the apparent zenith (AZ). Experiment 1 involved rotation on a centrifuge and settings of the AZ. Subjects were supine on the centrifuge, and their body position was varied in relation to the rotation axis so that the gravitoinertial resultant force at the otoliths was 1 or 1.2 g with the otolith organs positioned 50 or 100 cm from the axis of rotation. Their legs were also positioned in different configurations, flexed and elevated or extended, to create different distributions of blood and lymph. Experiment 2 involved (a) settings of the AZ for subjects positioned supine with legs fully extended or legs flexed and elevated to create a torsoward shift of blood and (b) settings of the subjective visual vertical for subjects horizontally positioned on their sides with legs extended or bent. Experiment 3 had subjects in the same body configurations as in Experiment 2 indicate when they were horizontal as they were rotated in pitch or roll about an inter-aural or naso-occipital axis. The experimental results for all three experiments demonstrated that both visual localization and apparent body horizontal are jointly determined by multimodal combinations of otolithic and somatosensory/proprioceptive stimulation. No evidence was found for non-overlapping or exclusive mechanisms determining one or the other. The subjective postural horizontal and AZ were affected in similar ways by comparable manipulations.

The elevator illusion results from the combination of body orientation and egocentric perception.

Perception of body orientation and apparent location of objects are altered when humans are using assisted means of locomotion and the resultant of the imposed acceleration and gravity is no longer aligned with the gravitational vertical. As the otolithic system cannot discriminate the acceleration of gravity from sustained inertial accelerations, individuals would perceive the resultant acceleration vector (GiA) as the vertical. However, when subjects are aligned on the GiA, an increase in the magnitude of GiA induced a lowering of the apparent visual horizon (i.e. "elevator illusion"). The main aim of this study was to quantify the contribution of body and egocentric perception in the elevator illusion. While being exposed to 1G and 1.3G and aligned on the GiA acceleration, subjects (N=20) were asked (1) to set a luminous target to the subjective horizon, (2) to set a luminous target on "straight ahead" position (egocentric task) and (3) to rotate a tilting tube to their subjective perception of body orientation. Results showed that increasing GiA lowered horizon and egocentric settings and induces a backward body tilt perception. Moreover, the elevator illusion can be expressed as the additive combination of two processes: one that is dependent on body tilt perception, and the other that is dependent on egocentric perception. Both misperceptions in hypergravity may be considered to be a consequence of excessive shearing of the otolith organs. However large inter-individual differences in body tilt perception were observed. This last result was discussed in terms of the contribution of extravestibular graviceptors.

Citrulline modulates muscle protein metabolism in old malnourished rats.

Protein energy malnutrition is common in the elderly, especially in hospitalized patients. The development of strategies designed to correct such malnutrition is essential. Our working hypothesis was that poor response to nutrition with advancing age might be related to splanchnic sequestration of amino acids, which implies that fewer amino acids reach the systemic circulation. Administration of citrulline, which is not taken up by the liver, can offer a means of increasing whole body nitrogen availability and, hence, improve nutritional status. Thirty old (19 mo) rats were submitted to dietary restriction (50% of food intake) for 12 wk. They were randomized into three groups: 10 rats (R group) were killed and 20 others refed (90% of food intake) for 1 wk with a standard diet (NEAA group) or a citrulline-supplemented diet (Cit group). Before being killed, the rats were injected with [(13)C]valine, and the absolute protein synthesis rate (ASR) was measured in the tibialis using the flooding-dose method. When the rats were killed, the tibialis was removed for protein content analysis. Blood was sampled for amino acid and insulin analysis. The standard diet did not have any effect on protein synthesis or on the protein content in the muscle. Citrulline supplementation led to higher protein synthesis and protein content in muscle (117 +/- 9, 120 +/- 14, and 163 +/- 4 mg/organ for protein content in R, NEAA, and Cit groups, P < 0.05). The ASR were 0.30 +/- 0.04, 0.31 +/- 0.04, and 0.56 +/- 0.10 mg/h in the three groups, respectively (R and NEAA vs. Cit, P < 0.05). Insulinemia was significantly higher in the Cit group. For the first time, a realistic therapeutic approach is proposed to improve muscle protein content in muscle in frail state related to malnutrition in aging.

The equivocal metabolic response to endotoxaemia in type 2 diabetic and obese ZDF rats.

AIMS/HYPOTHESIS: The metabolic and endocrine disturbances associated with obesity and type 2 diabetes may impair the normal metabolic response to injury. Our objective was to investigate amino acid metabolism in endotoxaemic type 2 diabetic obese rats. MATERIALS AND METHODS: A metabolic study was performed over 4 days using male Zucker diabetic fatty (ZDF) rats (fa/fa) and lean littermates (fa/+) divided into three groups: ad libitum-fed groups which underwent no treatment, lipopolysaccharide (LPS)-treated groups receiving E. coli LPS by i.p. injection, and pair-fed groups to the respective LPS groups. We evaluated the effect of endotoxaemia on body weight, food intake and tissue weights. Nitrogen loss and muscular proteolysis were measured daily by determination of urinary 3-methylhistidine (3-MH) excretion. Plasma, intestine and muscle amino acid levels were measured. RESULTS: The data showed that ad libitum-fed ZDF rats had lower plasma arginine and glutamine levels than ad libitum-fed control rats. Compared with control rats, the LPS-treated ZDF rats presented lower thymic involution, a lower 3-MH:creatinine ratio and higher cumulative nitrogen balance. CONCLUSIONS/INTERPRETATION: Against our working hypothesis, ZDF rats did not show an impaired metabolic response, and even appeared to be less sensitive to the stress.