DAOS

Disease-associated oligodendrocyte responses across neurodegenerative diseases

Oligodendrocyte dysfunction has been implicated in the pathogenesis of neurodegenerative diseases, so understanding oligodendrocyte activation states would shed light on disease processes. We identify three distinct activation states of oligodendrocytes from single-cell RNA sequencing (RNA-seq) of mouse models of Alzheimer's disease (AD) and multiple sclerosis (MS): DA1 (disease-associated1, associated with immunogenic genes), DA2 (disease-associated2, associated with genes influencing survival), and IFN (associated with interferon response genes). Spatial analysis of disease-associated oligodendrocytes (DAOs) in the cuprizone model reveals that DA1 and DA2 are established outside of the lesion area during demyelination and that DA1 repopulates the lesion during remyelination. Independent meta-analysis of human single-nucleus RNA-seq datasets reveals that the transcriptional responses of MS oligodendrocytes share features with mouse models. In contrast, the oligodendrocyte activation signature observed in human AD is largely distinct from those observed in mice. This catalog of oligodendrocyte activation states (http://research-pub.gene.com/OligoLandscape/) will be important to understand disease progression and develop therapeutic interventions.

Examining Physician Interactions with Disease Advocacy Organizations

Disease advocacy organizations (DAOs) have traditionally focused on raising awareness of rare diseases, providing educational resources to patients, and supporting patients and families. Previous research has described how scientists collaborate with DAOs, but few empirical data are available regarding the extent to which physicians interact with DAOs and how those interactions impact patient care. We conducted a national survey of 230 board-certified pediatric neurologists to assess their engagement with DAOs and their beliefs about the impact of DAOs on patient care. In that context, we evaluated a set of 24 items describing interactions between physicians and DAOs. Exploratory factor analysis produced a 19-item model capturing four types of physician-DAO engagement: (1) accessing or distributing DAO-produced materials (6 items, alpha = 0.80); (2) consulting on DAO activities (5 items, alpha = 0.81); (3) collaborating with DAOs on research activities (6 items, alpha = 0.80); and (4) co-producing scholarly materials with DAOs (2 items, alpha = 0.80). Our data indicate that physicians engage with DAOs in more frequent and diverse ways than has been previously reported. Almost all physicians in our sample had interacted directly with a DAO in some way, from low-effort activities such as visiting a DAO's website to deeper forms of engagement including coauthoring journal articles. These findings may provide a framework for bioethicists to characterize the nature and extent of physician interactions with advocacy organizations, which is critical for evaluating the ethical implications of physician-DAO relationships.

Comparative pharmacokinetic study of two kinds of altrenogest oral solutions for sows

This study was to compare the pharmacokinetic characteristics of domestic altrenogest oral solution (DAOS) or imported altrenogest oral solution (IAOS) in healthy sows. A single administration (1 mg/kg body weight) of DAOS or IAOS was performed in sixteen healthy sows according to a two-period crossover design. Plasma concentrations of altrenogest (AT) were measured by high performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS) and the concentration-time data of AT was analyzed by WINNONLIN 5.2. It was suggested that the main pharmacokinetic parameters of DAOS and IAOS were as follows: C_max was 227.59 ± 83.35 ng/mL and 152.83 ± 80.34 ng/mL, T_max was 1.16 ± 0.52 h and 1.58 ± 0.85 h, t_1/2 was 3.63 ± 0.72 h and 3.45 ± 0.63 h, MRT was 5.02 ± 0.79 h and 5.21 ± 0.87 h, AUC_0-t was 1050.23 ± 409.80 h·ng/mL and 778.22 ± 397.84 h·ng/mL, and AUC_0-∞ was 1060 h·ng/mL and 786 h·ng/mL, respectively. The relative bioavailability of DAOS was 134.9%. Above results indicated that oral DAOS was better absorbed than IAOS, C_max of DAOS was higher than that of IAOS (p < 0.05). However, there was no significant difference in the main pharmacokinetic parameters between oral DAOS and IAOS (p > 0.05). Our data confirmed that the absorption, fast elimination and bioavailability of DAOS in sows were better than those of IAOS.

Progressive apraxia of speech in Quebec French speakers: A case series

Background: The term progressive apraxia of speech (PAOS) is used to describe speakers presenting with isolated or dominant apraxia of speech in the context of a neurodegenerative syndrome, including primary progressive apraxia of speech (PPAOS) and dominant progressive apraxia of speech (DAOS), respectively. Its motor speech profile has been increasingly explored in the last decade, but description remains vague and very English oriented, although the effect of speakers' language on motor speech phenotypes is increasingly recognized. Although some studies suggest that speakers presenting with isolated PAOS (PPAOS) versus dominant PAOS with concomitant aphasia (DAOS) should be differentiated, distinct characteristics of the two presentations are unclear. Furthermore, a careful description of their clinical presentation in languages other than English is required.
Aims: To describe the motor speech characteristics of Quebec French-speaking participants with prominent PAOS and to explore the communication profile of those presenting more specifically with isolated PAOS (PPAOS), and with dominant PAOS and concomitant aphasia (DAOS).
Methods & procedures: A thorough effort to recruit all speakers presenting with PAOS in the larger population areas of the province of Quebec was conducted over a 3-year span. A total of nine participants with PAOS (pwPAOS; PPAOS = 5, DAOS = 4) underwent a comprehensive language and motor speech assessment, and a cognitive screening. Their performance was compared with 30 matched healthy controls.
Outcomes & results: As a group, pwPAOS differed from healthy speakers on all acoustic and perceptual measures. The PPAOS and PAOS subgroups were similar on several measures, but participants from the PPAOS subgroup tended to perform better on articulatory measures and maximum speech rate tasks.
Conclusions & implications: This study provides an in-depth analysis of motor speech characteristics of PAOS in Quebec French speakers and adds further evidence for the differentiation of PPAOS and DAOS. Combining simple perceptual and acoustic analyses represent a promising approach to distinguish the two variants and identify treatment targets. What this paper adds What is already known on this subject Progressive apraxia of speech (PAOS) is a neurodegenerative syndrome characterized by progressive and initially isolated or dominant apraxia of speech (primary progressive apraxia of speech [PPAOS] and dominant progressive apraxia of speech [DAOS], respectively). Studies mostly report articulatory and prosodic deficits in PAOS, but concomitant deficits such as dysarthria and executive dysfunction are also reported. The description of motor speech skills in PAOS remains vague and English-oriented. Studies suggest that speakers presenting with isolated PAOS vs dominant PAOS with concomitant aphasia should be differentiated, but distinct characteristics of the two presentations are unclear. What this study adds to existing knowledge To the best of the authors' knowledge, this study is the first to report transversal data of Quebec-French participants with PPAOS and DAOS. Moreover, this study is a first step towards identifying potential characteristics that could facilitate the diagnosis of PPAOS and DAOS in Quebec French. It makes a significant contribution to our understanding of progressive apraxia of speech in different cultural languages. What are the potential or actual clinical implications of this work? This study also initiates the search for sensitive tasks for the diagnosis of those speakers (which is an important process), in addition to identifying the core characteristics of PAOS, DAOS, and PPAOS in the development of an assessment battery for this population.

Quantitative Analysis of Agrammatism in Agrammatic Primary Progressive Aphasia and Dominant Apraxia of Speech

Purpose: The aims of the study were to assess and compare grammatical deficits in written and spoken language production in subjects with agrammatic primary progressive aphasia (agPPA) and in subjects with agrammatism in the context of dominant apraxia of speech (DAOS) and to investigate neuroanatomical correlates.
Method: Eight agPPA and 21 DAOS subjects performed the picture description task of the Western Aphasia Battery (WAB) both in writing and orally. Responses were transcribed and coded for linguistic analysis. agPPA and DAOS were compared to 13 subjects with primary progressive apraxia of speech (PPAOS) who did not have agrammatism. Spearman correlations were performed between the written and spoken variables. Patterns of atrophy in each group were compared, and relationships between the different linguistic measures and integrity of Broca's area were assessed.
Results: agPPA and DAOS both showed lower mean length of utterance, fewer grammatical utterances, more nonutterances, more syntactic and semantic errors, and fewer complex utterances than PPAOS in writing and speech, as well as fewer correct verbs and nouns in speech. Only verb ratio and proportion of grammatical utterances correlated between modalities. agPPA and DAOS both showed greater involvement of Broca's area than PPAOS, and atrophy of Broca's area correlated with proportion of grammatical and ungrammatical utterances and semantic errors in writing and speech.
Conclusions: agPPA and DAOS subjects showed similar patterns of agrammatism, although subjects performed differently when speaking versus writing. Integrity of Broca's area correlates with agrammatism.