Levodopa-Associated Barking Vocalizations.
Ontology highlight
ABSTRACT:
SUBMITTER: Prasad S
PROVIDER: S-EPMC8175812 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
Levodopa-Associated Barking Vocalizations.
Prasad Shweta S Pal Pramod Kumar PK
Journal of movement disorders 20201031 2
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Project description:A promising approach to understanding the mechanistic basis of speech is to study disorders that affect speech without compromising other cognitive or motor functions. Stuttering, also known as stammering, has been linked to mutations in the lysosomal enzyme-targeting pathway, but how this remarkably specific speech deficit arises from mutations in a family of general "cellular housekeeping" genes is unknown. To address this question, we asked whether a missense mutation associated with human stuttering causes vocal or other abnormalities in mice. We compared vocalizations from mice engineered to carry a mutation in the Gnptab (N-acetylglucosamine-1-phosphotransferase subunits alpha/beta) gene with wild-type littermates. We found significant differences in the vocalizations of pups with the human Gnptab stuttering mutation compared to littermate controls. Specifically, we found that mice with the mutation emitted fewer vocalizations per unit time and had longer pauses between vocalizations and that the entropy of the temporal sequence was significantly reduced. Furthermore, Gnptab missense mice were similar to wild-type mice on an extensive battery of non-vocal behaviors. We then used the same language-agnostic metrics for auditory signal analysis of human speech. We analyzed speech from people who stutter with mutations in this pathway and compared it to control speech and found abnormalities similar to those found in the mouse vocalizations. These data show that mutations in the lysosomal enzyme-targeting pathway produce highly specific effects in mouse pup vocalizations and establish the mouse as an attractive model for studying this disorder.
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Project description:Chronic levodopa treatment for Parkinson's disease often results in the development of abnormal involuntary movement, known as L-dopa-induced dyskinesia (LIDs). Studies suggest that LIDs may be associated with aberrant corticostriatal plasticity. Using in vivo extracellular recordings from identified Type I and Type II medium spiny striatal neurons, chronic L-dopa treatment was found to produce abnormal corticostriatal information processing. Specifically, after chronic L-dopa treatment in dopamine-depleted rats, there was a transition from a cortically evoked long-term depression (LTD) to a complementary but opposing form of plasticity, long-term potentiation, in Type II "indirect" pathway neurons. In contrast, LTD could still be induced in Type I neurons. Interestingly, the one parameter that correlated best with dyskinesias was the inability to de-depress established LTD in Type I medium spiny striatal neurons. Taken as a whole, we propose that the induction of LIDs is due, at least in part, to an aberrant induction of plasticity within the Type II indirect pathway neurons combined with an inability to de-depress established plastic responses in Type I neurons. Such information is critical for understanding the cellular mechanisms underlying one of the major caveats to L-dopa therapy.
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Project description:OBJECTIVES:Several trials have been published examining the role of antibiotics in dog bite wound management. A meta-analysis of these suggests that there is very little benefit to routine antibiotic prescription in these patients. All papers however incorporated rigorous wound care regimens involving large volume irrigation. METHODS:The authors undertook a telephone survey to investigate wound care and prescribing practice in bite wound management in accident and emergency and minor injury units in the Yorkshire region. RESULTS:Twenty one departments were contacted. Only 10% of departments routinely irrigate these wounds. Antibiotics are prescribed routinely in 71%. CONCLUSIONS:Management of dog bite wounds would not seem to be evidence based in most departments in this sample.
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Project description:Over half of US children are enrolled in preschools, where the quantity and quality of language input from teachers are likely to affect children's language development. Leveraging repeated objective measurements, we examined the rate per minute and phonemic diversity of child and teacher speech-related vocalizations in preschool classrooms and their association with children's end-of-year receptive and expressive language abilities measured with the Preschool Language Scales (PLS-5). Phonemic diversity was computed as the number of unique consonants and vowels in a speech-related vocalization. We observed three successive cohorts of 2.5-3.5-year-old children enrolled in an oral language classroom that included children with and without hearing loss (N = 29, 16 girls, 14 Hispanic). Vocalization data were collected using child-worn audio recorders over 34 observations spanning three successive school years, yielding 21.53 mean hours of audio recording per child. The rate of teacher vocalizations positively predicted the rate of children's speech-related vocalizations while the phonemic diversity of teacher vocalizations positively predicted the phonemic diversity of children's speech-related vocalizations. The phonemic diversity of children's speech-related vocalizations was a stronger predictor of end-of-year language abilities than the rate of children's speech-related vocalizations. Mediation analyses indicated that the phonemic diversity of teacher vocalizations was associated with children's receptive and expressive language abilities to the extent that it influenced the phonemic diversity of children's own speech-related vocalizations. The results suggest that qualitatively richer language input expands the phonemic diversity of children's speech, which in turn is associated with language abilities.
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Project description:There is a notable shift toward more repression and criminalization in sex work policies, in Europe and elsewhere. So-called neo-abolitionism reduces sex work to trafficking, with increased policing and persecution as a result. Punitive "demand reduction" strategies are progressively more popular. These developments call for a review of what we know about the effects of punishing and repressive regimes vis-à-vis sex work. From the evidence presented, sex work repression and criminalization are branded as "waterbed politics" that push and shove sex workers around with an overload of controls and regulations that in the end only make things worse. It is illustrated how criminalization and repression make it less likely that commercial sex is worker-controlled, non-abusive, and non-exploitative. Criminalization is seriously at odds with human rights and public health principles. It is concluded that sex work criminalization is barking up the wrong tree because it is fighting sex instead of crime and it is not offering any solution for the structural conditions that sex work (its ugly sides included) is rooted in. Sex work repression travels a dead-end street and holds no promises whatsoever for a better future. To fight poverty and gendered inequalities, the criminal justice system simply is not the right instrument. The reasons for the persistent stigma on sex work as well as for its present revival are considered.
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Project description:Homonyms are a critical test case for investigating how the brain resolves ambiguity in language and, more generally, how context influences semantic processing. Previous neuroimaging studies have associated processing of homonyms with greater engagement of regions involved in executive control of semantic processing. However, the precise role of these areas and the involvement of semantic representational regions in homonym comprehension remain elusive. We addressed this by combining univariate and multivariate fMRI analyses of homonym processing. We tested whether multi-voxel activation patterns could discriminate between presentations of the same homonym in different contexts (e.g., bark following tree vs. bark following dog). The ventral anterior temporal lobe, implicated in semantic representation but not previously in homonym comprehension, showed this meaning-specific coding, despite not showing increased mean activation for homonyms. Within inferior frontal gyrus (IFG), a key site for semantic control, there was a dissociation between pars orbitalis, which also showed meaning-specific coding, and pars triangularis, which discriminated more generally between semantically related and unrelated word pairs. IFG effects were goal-dependent, only occurring when the task required semantic decisions, in line with a top-down control function. Finally, posterior middle temporal cortex showed a hybrid pattern of responses, supporting the idea that it acts as an interface between semantic representations and the control system. The study provides new evidence for context-dependent coding in the semantic system and clarifies the role of control regions in processing ambiguity. It also highlights the importance of combining univariate and multivariate neuroimaging data to fully elucidate the role of a brain region in semantic cognition.
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