Body mass index influences the response to infliximab in ankylosing spondylitis

INTRODUCTION: The excess of adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetic consequences. The aim of this study was to determine whether body mass index (BMI) affects response to infliximab (IFX) in ankylosing spondylitis (AS) patients. METHODS: In 155 patients retrospectively included with active AS, the BMI was calculated before initiation of IFX treatment (5 mg/kg intravenously). After 6 months of treatment, changes from baseline in BASDAI, Visual Analogue Scale (VAS) pain, C-reactive protein (CRP) level, and total dose of nonsteroidal antiinflammatory drug (NSAID) were dichotomized with a threshold corresponding to a decrease of 50% of initial level of the measure, into binary variables assessing response to IFX (BASDAI50, VAS50, CRP50, NSAID50). Whether the BMI was predictive of the response to IFX therapy according to these definitions was assessed with logistic regression. RESULTS: Multivariate analysis found that a higher BMI was associated with a lower response for BASDAI50 (P = 0.0003; OR, 0.87; 95% CI (0.81 to 0.94)), VAS50 (P < 0.0001; OR, 0.87; 95% CI (0.80 to 0.93)); CRP50 (P = 0.0279; OR, 0.93; 95% CI (0.88 to 0.99)), and NSAID50 (P = 0.0077; OR, 0.91; 95% CI (0.85 to 0.97)), criteria. According to the three WHO BMI categories, similar results were found for BASDAI50 (77.6%, 48.9%, and 26.5%; P < 0.0001), VAS50 (72.6%, 40.4%, and 16.7%; P < 0.0001); CRP50 (87.5%, 65.7%, and 38.5%; P = 0.0001), and NSAID50 (63.2%, 51.5%, and 34.6%; P = 0.06). CONCLUSIONS: This study provides the first evidence that a high BMI negatively influences the response to IFX in AS. Further prospective studies, including assessment of the fat mass, pharmacokinetics, and adipokines dosages are mandatory to elucidate the role of obesity in AS IFX response

Integrating hydrological features and genetically validated occurrence data in occupancy modeling of an endemic and endangered semi-aquatic mammal species, Galemys pyrenaicus, in a Pyrenean catchment

As freshwater habitats are among the most endangered, there is an urgent need to identify critical areas for conservation, especially those that are home to endangered species. The Pyrenean desman (Galemys pyrenaicus) is a semi-aquatic mammal whose basic ecological requirements are largely unknown, hindering adequate conservation planning even though it is considered as a threatened species. Species distribution modelling is challenging for freshwater species. Indeed, the complexity of aquatic ecosystems (e.g., linear and hierarchical ordering) must be taken into account as well as imperfect sampling. High-quality and relevant hydrological descriptors should also be used. To understand the influence of environmental covariates on the occupancy and detection of the Pyrenean desman, we combine both a robust sign-survey data set (i.e. with genetic validation ensuring true presence information) and a hydrological model to simulate the flow regime across a whole catchment. Markovian site-occupancy analysis, taking into account sign detection and based on spatially adjacent replicates, indicated a positive influence of heterogeneity of substrate and shelters, and a negative influence of flow variability on Pyrenean desman detection. This valuable information should help to improve monitoring programs for this endangered species. Our results also highlighted a spatially clustered distribution and a positive influence of stream flow and number of tributaries on occupancy. Hence, modifications of flow regime (e.g. hydropower production, irrigation, climate change) and habitat fragmentation appear to be major threats for this species, altering the connectivity between tributaries and the mainstream river as well as between adjacent sub-catchments

Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes

A deficiency in pejvakin, a protein of unknown function, causes a strikingly heterogeneous form of human deafness. Pejvakin-deficient (Pjvk(-/-)) mice also exhibit variable auditory phenotypes. Correlation between their hearing thresholds and the number of pups per cage suggest a possible harmful effect of pup vocalizations. Direct sound or electrical stimulation show that the cochlear sensory hair cells and auditory pathway neurons of Pjvk(-/-) mice and patients are exceptionally vulnerable to sound. Subcellular analysis revealed that pejvakin is associated with peroxisomes and required for their oxidative-stress-induced proliferation. Pjvk(-/-) cochleas display features of marked oxidative stress and impaired antioxidant defenses, and peroxisomes in Pjvk(-/-) hair cells show structural abnormalities after the onset of hearing. Noise exposure rapidly upregulates Pjvk cochlear transcription in wild-type mice and triggers peroxisome proliferation in hair cells and primary auditory neurons. Our results reveal that the antioxidant activity of peroxisomes protects the auditory system against noise-induced damage

Thérapie génique des surdités humaines

Durant les vingt dernières années, des progrès considérables ont été accomplis dans la compréhension de la pathogénie des diverses formes de surdités, congénitales ou acquises. L’identification de gènes responsables de surdité chez l’homme, l’ingénierie et la caractérisation fonctionnelle de modèles murins de certaines formes de surdité humaine ont également fait progresser la physiologie moléculaire des cellules sensorielles auditives. Ces avancées ont ouvert la voie au développement de nouvelles stratégies thérapeutiques, alternatives aux prothèses conventionnelles (amplificateurs du son) ou aux implants cochléaires permettant d’améliorer la fonction auditive. Dans cette revue, nous présentons d’abord les progrès accomplis sur le chemin de la thérapie génique des surdités au cours de la dernière décennie. Nous discutons ensuite le potentiel de la thérapie génique pour traiter les surdités acquises ou héréditaires, ainsi que les principaux obstacles qui doivent être surmontés avant qu’une application clinique puisse être envisagée

Whistled Phoneme Categorization: the Effect of Vowel Space Range

We explore whistled vowel categorization by untrained listeners, focusing specifically on the impact of the different vocalic frequency ranges of two whistlers (for the vowels /i/, /e/, /a/, /o/) and the effect of training on performance. In the experiment, we included stimuli that show inter-individual and intra-individual variations of production. In the analyses we looked at the whistler identity effect and at the learning effect through the experiment for the studied vowels. The results showed an effect of the whistler, where the larger vocalic range led to improved categorization, and highlighted the robustness of the vowel recognition hierarchy. There was no general learning effect, albeit for one vowel and for the whistler with a narrower vocalic range. This study provides insight into one's representation of the vowel space in non-tonal languages

Categorization of Whistled Consonants by French Speakers

International audienceWhistled speech is a form of modified speech where some frequencies of vowels and consonants are augmented and transposed to whistling, modifying the timbre and the construction of each phoneme. These transformations cause only some elements of the signal to be intelligible for naive listeners, which, according to previous studies, includes vowel recognition. Here, we analyze naive listeners’ capacities for whistled consonant categorization for four consonants: /p/, /k/, /t/ and /s/ by presenting the findings of two behavioral experiments. Though both experiments measure whistled consonant categorization, we used modified frequencies — lowered with a phase vocoder — of the whistled stimuli in the second experiment to better identify the relative nature of pitch cues employed in this process. Results show that participants obtained approximately 50% of correct responses (when chance is at 25%). These findings show specific consonant preferences for “s” and “t” over “k” and “p”, specifically when stimuli is unmodified. Previous research on whistled consonants systems has often opposed “s” and “t” to “k” and “p”, due to their strong pitch modulations. The preference for these two consonants underlines the importance of these cues in phoneme processing

Whistled Vowel Identification by French Listeners

International audienceIn this paper, we analyzed whistled vowel categorization by native French listeners. Whistled speech, a natural, yet modified register of speech, is used here as a tool to investigate perceptual processes in languages. We focused on four whistled vowels: /i, e, a, o/. After a detailed description of the vowels, we built and ran a behavioral experiment in which we asked native French speakers to categorize whistled vowel stimuli in which we introduced intra- and inter- production variations. In addition, half of the participants performed the experiment in person (at the laboratory) while the other half participated online, allowing us to evaluate the impact of the testing set up. Our results confirm that the categorization rate of whistled vowels is above chance. They reveal significant differences in performance for different vowels and suggest an influence of certain acoustic parameters from the whistlers’ vowel range on categorization. Moreover, no effect or interaction was found for testing location and circumstances in our data set. This study confirms that whistled stimuli are a useful tool for studying how listeners process modified speech and which parameters impact sound categorization

Testing perceptual flexibility in speech through the categorization of whistled Spanish consonants by French speakers

International audienceWhistled speech is a form of modified speech where, in non-tonal languages, vowels and consonants are augmented and transposed to whistled frequencies, simplifying their timbre. According to previous studies, these transformations maintain some level of vowel recognition for naive listeners. Here, in a behavioral experiment, naive listeners' capacities for the categorization of four whistled consonants (/p/, /k/, /t/, and /s/) were analyzed. Results show patterns of correct responses and confusions that provide new insights into whistled speech perception, highlighting the importance of frequency modulation cues, transposed from phoneme formants, as well as the perceptual flexibility in processing these cues