Atypical vocal quality in women with the FMR1 premutation: an indicator of impaired sensorimotor control.

Women with the FMR1 premutation are susceptible to motor involvement related to atypical cerebellar function, including risk for developing fragile X tremor ataxia syndrome. Vocal quality analyses are sensitive to subtle differences in motor skills but have not yet been applied to the FMR1 premutation. This study examined whether women with the FMR1 premutation demonstrate differences in vocal quality, and whether such differences relate to FMR1 genetic, executive, motor, or health features of the FMR1 premutation. Participants included 35 women with the FMR1 premutation and 45 age-matched women without the FMR1 premutation who served as a comparison group. Three sustained /a/ vowels were analyzed for pitch (mean F0), variability of pitch (standard deviation of F0), and overall vocal quality (jitter, shimmer, and harmonics-to-noise ratio). Executive, motor, and health indices were obtained from direct and self-report measures and genetic samples were analyzed for FMR1 CGG repeat length and activation ratio. Women with the FMR1 premutation had a lower pitch, larger pitch variability, and poorer vocal quality than the comparison group. Working memory was related to harmonics-to-noise ratio and shimmer in women with the FMR1 premutation. Vocal quality abnormalities differentiated women with the FMR1 premutation from the comparison group and were evident even in the absence of other clinically evident motor deficits. This study supports vocal quality analyses as a tool that may prove useful in the detection of early signs of motor involvement in this population.

Comparison of Linguistic Error Production in Conversational Language Among Boys With Fragile X Syndrome + Autism Spectrum Disorder and Autistic Boys.

PURPOSE: Expressive language impairments are common among school-age boys with fragile X syndrome (FXS) and autistic boys. Given the high co-occurrence of autism spectrum disorder (ASD) among individuals with FXS, cross-condition comparisons can elucidate the specificity of such impairments as they relate to ASD. Language samples can provide fruitful information regarding individuals' grammatical skills in less structured formats relative to standardized measures. This study examined grammatical errors produced during a conversational language sample among 20 boys with FXS and co-occurring ASD (FXS + ASD) and 19 autistic boys matched on ASD severity. METHOD: Language samples were coded for omissions and errors at the word and utterance levels. Participants' grammatical errors were also compared to separate mental age-matched and mean length of utterance-matched boys from a reference database. RESULTS: Boys with FXS + ASD and autistic boys produced similar rates of errors across all categories. Relative to their matched comparison groups, boys with FXS + ASD and autistic boys produced significantly more omissions during conversation. CONCLUSIONS: These findings suggest that omissions may be a unique grammatical marker associated with the ASD phenotype. Further examination of omissions across diagnostic groups would aid in clarifying the specificity of omissions in the language phenotype of ASD.

Acute Occupational and Physical Therapy for Patients With COVID-19: A Retrospective Cohort Study.

OBJECTIVE: To describe the function of patients with COVID-19 admitted to an acute care hospital early in the pandemic and to characterize change in function among those admitted to intensive care units (ICU) and to non-critical care services. DESIGN: This descriptive, retrospective cohort study examined patients infected with SARS-CoV-2 admitted to a tertiary care medical center during the first wave of the pandemic in 2020. Included patients were stratified into 4 cohorts based on whether or not they received therapy during their hospitalization and whether or not their hospitalization included time in the ICU. Data on demographic characteristics, functional impairments, medical interventions, and functional outcomes were collected. SETTING: Hospital. PARTICIPANTS: 432 adult patients were included in this study (N=432). RESULTS: ICU patients receiving therapy were more likely to have impaired cognition, impaired strength, and impaired sensation than non-ICU patients receiving therapy. Patients made improvements from evaluation to discharge on the Functional Status Score for the ICU, Activity Measure for Post-Acute Care Daily Activity, and AM-PAC Basic Mobility Short Forms. CONCLUSION: Patients admitted with COVID-19 experienced significant functional impairments but also demonstrated improvement during the course of their hospitalizations. This study can facilitate health care provider awareness of the detrimental functional effects of COVID-19 and the potential role of rehabilitation services for these patients.

Brief Report: Linguistic Mazes and Perseverations in School-Age Boys with Fragile X Syndrome and Autism Spectrum Disorder and Relationships with Maternal Maze Use.

Autism spectrum disorder (ASD) and fragile X syndrome (FXS) are neurodevelopmental disorders with overlapping pragmatic language impairments. Prior work suggests pragmatic language differences may run in families. This study examined specific pragmatic difficulties (i.e., linguistic mazes and perseverations) in boys (9-18 years) with idiopathic ASD (n = 26) and FXS+ASD (n = 29), and relationships with maternal maze use. Language samples were obtained separately for boys and mothers. Nonparametric analyses suggested that boys largely did not differ in their rates of mazes, but that boys with FXS+ASD exhibited more perseverations. Mazes were correlated between fragile X dyads. Maternal mazes were correlated with child perseverations among idiopathic ASD dyads. These findings have implications for the etiological significance of ASD-related language phenotypes.

Family as a Context for Child Development: Mothers with the FMR1 Premutation and Their Children with Fragile X Syndrome.

Fragile X syndrome (FXS) is a genetic disorder caused by changes of the FMR1 gene that is passed along among families. A range of developmental processes may be impacted with wide variation in abilities across individuals with FXS. Mothers of children with FXS are often carriers of a "premutation" expansion on the FMR1 gene, which is associated with its own clinical phenotype. These maternal features may increase individual and family vulnerabilities, including increased risk for depression and anxiety disorders and difficulties in social and cognitive ability. These characteristics may worsen with age, and potentially interact with a child's challenging behaviors and with family dynamics. Thus, families of children with FXS may experience unique challenges related to genetic risk, manifested across both children and parents, that should be considered in therapeutic planning to optimize outcomes for children and their families. In this article, we review core features of the FMR1 premutation as expressed in mothers and aspects of the family environment that interface with developmental outcomes of children with FXS. Recommendations for family-centered support services are discussed.

"Are We Done Yet?" Question-Asking in Boys With Fragile X Syndrome and Idiopathic Autism Spectrum Disorder.

Purpose Question-asking serves as a tool to learn new information and is important in both academic and social settings. Boys with idiopathic autism spectrum disorder (ASD) and boys with fragile X syndrome and comorbid ASD (FXS + ASD) have similar social communication deficits, which may have downstream effects on their question-asking ability. This study examined question-asking in school-age boys with idiopathic ASD and FXS + ASD, including the role of ASD severity, expressive grammatical complexity (measured by mean length of utterance [MLU]), and IQ. Method Twenty-five boys with FXS + ASD and 21 boys with idiopathic ASD (ages 9-16 years) were included in this study. Autism Diagnostic Observation Schedule assessments were transcribed and coded for the frequency, function, and appropriateness of spontaneous questions asked. We examined group differences in these aspects of question-asking and relationships between question-asking and ASD severity, MLU, and IQ within each group. Results Boys with FXS + ASD asked more questions than boys with idiopathic ASD, although boys with idiopathic ASD asked a higher proportion of appropriate questions. Boys with idiopathic ASD also asked the examiner more personal questions than the boys with FXS + ASD. ASD severity and MLU were related to the proportion of clarification questions in FXS + ASD, and ASD severity was also related to the proportion of personal questions in this group. For the boys with idiopathic ASD, ASD severity was related to the total number of questions asked. Conclusions Our findings highlight similarities and differences between boys with FXS + ASD and idiopathic ASD in their spontaneous question production and indicate that ASD severity and grammatical language are differentially important for question-asking. This study has implications for targeted treatment in question-asking skills for boys with FXS + ASD and ASD.

Expressive language abilities of boys with idiopathic autism spectrum disorder and boys with fragile X syndrome + autism spectrum disorder: Cross-context comparisons.

Background and aims: Understanding the unique expressive language profiles of children with phenotypically similar, but distinct neurodevelopmental disorders, such as idiopathic autism spectrum disorder and fragile X syndrome with a co-diagnosis of autism spectrum disorder (fragile X syndrome + autism spectrum disorder), has both clinical and theoretical implications. However, comparative studies of these two clinical groups have been limited, and results have been inconsistent, partially as a result of different assessment methods being utilized. Thus, the current study compared the expressive language profiles of boys with idiopathic autism spectrum disorder and boys with fragile X syndrome + autism spectrum disorder and examined whether a similar linguistic profile emerged across different language sampling contexts: a semi-structured conversation and the Autism Diagnostic Observation Schedule. Methods: Eighteen boys with autism spectrum disorder (Mage = 13.25 years) and 19 boys with fragile X syndrome + autism spectrum disorder (Mage = 12.19 years), matched on autism spectrum disorder symptom severity and similar in terms of chronological age and mean length of utterance, participated in this study. Boys produced two language samples: one semi-structured conversation and one taken from the Autism Diagnostic Observation Schedule. Language samples were coded for talkativeness, lexical diversity, mean length of utterance, intelligibility, and repetitive or perseverative language. Results: Analyses revealed that boys with autism spectrum disorder produced language samples that were more lexically diverse and intelligible, and that included less topic perseveration compared to boys with fragile X syndrome + autism spectrum disorder. With regards to sampling context, boys in both groups were more talkative and produced longer and more intelligible utterances in their conversation sample compared to their Autism Diagnostic Observation Schedule sample. However, boys with autism spectrum disorder and fragile X syndrome + autism spectrum disorder used a higher proportion of topic perseveration during the conversation sample. Conclusions: Overall, we found similarities as well as distinctions in the expressive language profiles of boys with fragile X syndrome + autism spectrum disorder and boys with idiopathic autism spectrum disorder. Moreover, the Autism Diagnostic Observation Schedule sample elicited a relatively different language profile than the conversation sample for boys in both groups. Implications: These findings help to further elucidate the unique language phenotypes of boys with idiopathic autism spectrum disorder and boys with fragile X syndrome + autism spectrum disorder. Moreover, our findings indicate that multiple language samples may be needed to obtain a comprehensive account of a child's expressive language ability.

Conversational Language Is a Predictor of Vocational Independence and Friendships in Adults with ASD.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder, impacting social communication and in some individuals, aspects of language such as vocabulary diversity. However, we have only a limited understanding of the verbal language abilities of adults with ASD. The present longitudinal study examined conversational language and its impact on vocational independence and friendship status measured 5 years later in a sample of 84 adults with ASD. After controlling for IQ and childhood language, vocabulary diversity (a measure of structural language) predicted vocational independence and having friendships, while topic maintenance (a measure of social communication) predicted friendships. These findings highlight the importance of adult conversational language abilities for adult outcomes and quality of life.

A Review of Language, Executive Function, and Intervention in Autism Spectrum Disorder.

Difficulties with both executive functions and language skills are common but variable in autism spectrum disorder (ASD). Executive functions and language skills are related to one another, such that vocabulary, syntax, and pragmatics are related to domains of working memory, shifting, and inhibition in ASD, although the directionality of these relationships remains unclear. Moreover, interventions that target pragmatic ability have been found to improve executive function skills, and conversely, executive function interventions are linked with improvements in social skills in children with ASD. We review the literature on executive functions, language skills, and their relationship in ASD; discuss factors that may be driving inconsistent findings; and explore clinical applications from the research thus far.

Urinary tract colonization is enhanced by a plasmid that regulates uropathogenic Acinetobacter baumannii chromosomal genes.

Multidrug resistant (MDR) Acinetobacter baumannii poses a growing threat to global health. Research on Acinetobacter pathogenesis has primarily focused on pneumonia and bloodstream infections, even though one in five A. baumannii strains are isolated from urinary sites. In this study, we highlight the role of A. baumannii as a uropathogen. We develop the first A. baumannii catheter-associated urinary tract infection (CAUTI) murine model using UPAB1, a recent MDR urinary isolate. UPAB1 carries the plasmid pAB5, a member of the family of large conjugative plasmids that represses the type VI secretion system (T6SS) in multiple Acinetobacter strains. pAB5 confers niche specificity, as its carriage improves UPAB1 survival in a CAUTI model and decreases virulence in a pneumonia model. Comparative proteomic and transcriptomic analyses show that pAB5 regulates the expression of multiple chromosomally-encoded virulence factors besides T6SS. Our results demonstrate that plasmids can impact bacterial infections by controlling the expression of chromosomal genes.

The rpf/DSF signalling system of Stenotrophomonas maltophilia positively regulates biofilm formation, production of virulence-associated factors and ß-lactamase induction.

Stenotrophomonas maltophilia is a multidrug-resistant opportunistic pathogen. S. maltophilia quorum-sensing system is mediated by the diffusible signal factor (DSF), which synthesis depends on rpfF. It has been reported that rpfF disruption in S. maltophilia K279a leads to a loss of DSF synthesis, reduced levels of extracellular protease, swarming motility and virulence in the Galleria mellonella model. The aim of this work was to attain a deeper knowledge of the role of the rpf/DSF signalling system in S. maltophilia biofilm formation, phenotypic traits associated with biofilm development and virulence and antimicrobial susceptibility. To this end, comparative studies were conducted on S. maltophilia K279a and K279arpfF. The results presented here put in evidence the positive role of DSF in bacterial growth, biofilm formation, swimming and twitching motilities, DNAse, lipases and siderophores production as well as resistance to oxidative stress. Interestingly, DSF seems to be essential for the development of the spatially organised structure seen in mature biofilms. Therefore, DSF from S. maltophlia K279a positively regulates biofilm formation and virulence. Furthermore, DSF is necessary for the induction of L1 and L2 ß-lactamase production in K279a. This is the first evidence of the role of the rpf/DSF signalling system in S. maltophilia ß-lactam resistance.

The use of demonstratives and personal pronouns in fragile X syndrome and autism spectrum disorder.

Demonstratives (e.g. here, that, these) and personal pronouns are early developing components of language, which are often impaired in young children with autism spectrum disorder (ASD). Additionally, demonstrative and personal pronoun use are linked to joint attention and language ability early in life for individuals with ASD. Fragile X syndrome (FXS) is a genetic disorder with a significant amount of overlap in its behavioural phenotype with ASD. The present study examined demonstrative and personal pronoun production during a conversation sample in adolescent boys with ASD and adolescent boys with FXS with a co-diagnosis of ASD (FXS+ASD). Findings indicated that grammatical complexity was related to both qualitative and quantitative aspects of demonstrative and personal pronoun production in boys with ASD, while grammatical complexity was related to the total number of demonstratives and personal pronouns produced in the boys with FXS+ASD. ASD severity was not related to demonstrative or personal pronoun production in ASD, although it was negatively correlated with the total number of personal pronouns produced by the boys with FXS. Additionally, groups did not differ significantly in production of personal pronouns, but they did differ significantly in multiple aspects of demonstrative use. Findings suggest that these groups produce similar rates of personal pronouns in the school-age years, while production of demonstratives differentiates these groups. This study contributes to the knowledge of the language phenotypes of idiopathic ASD and FXS+ASD, and provides implications for intervention targets for school-age children with these disorders.

Stenotrophomonas maltophilia isolated from patients exposed to invasive devices in a university hospital in Argentina: molecular typing, susceptibility and detection of potential virulence factors.

Purpose. The aim of this work was to investigate the presence of selected potential virulence factors, susceptibility and clonal relatedness among 63 Stenotrophomonas maltophilia isolates recovered from patients exposed to invasive devices in a university hospital in Argentina between January 2004 and August 2012.Methodology. Genetic relatedness was assessed by enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) and pulsed-field gel electrophoresis (PFGE). Isolates were characterized by antimicrobial resistance, the presence and/or expression of potential virulence determinants, and virulence in the Galleria mellonella model.Results/Key findings. ERIC-PCR generated 52 fingerprints, and PFGE added another pattern. Resistance to trimethoprim-sulfamethoxazole (6.35 %), levofloxacin (9.52 %) and ciprofloxacin (23.80 %) was detected. All isolates were susceptible to minocycline. All isolates were lipase, protease and siderophore producers, while all but Sm61 formed biofilms. However, 11/63 isolates did not amplify the major extracellular protease-coding gene (stmPr1). Sm61 is an stmPr1-negative isolate, and showed (as did Sm13 and the reference strain K279a) strong proteolysis and siderophore production, and high resistance to hydrogen peroxide. The three isolates were virulent in the G. mellonella model, while Sm10, a low-resistance hydrogen peroxide stmPr1-negative isolate, and weak proteolysis and siderophore producer, was not virulent.Conclusion. This is the first epidemiological study of the clonal relatedness of S. maltophilia clinical isolates in Argentina. Great genomic diversity was observed, and only two small clusters of related S. maltophilia types were found. Minocycline and trimethoprim-sulfamethoxazole were the most active agents. S. maltophilia virulence in the G. mellonella model is multifactorial, and further studies are needed to elucidate the role of each potential virulence factor.

Gaze avoidance and perseverative language in fragile X syndrome and autism spectrum disorder: brief report.

Gaze avoidance and perseverative language impact pragmatics in autism spectrum disorder (ASD) and fragile X syndrome (FXS). We examined these features during conversation samples in boys with ASD (n = 10) and boys with FXS and ASD (FXS+ASD; n = 10). Both groups had similar high rates of gaze avoidance and topic and conversation device perseverations, yet these features were not correlated with one another. Boys with FXS+ASD produced a higher proportion of single utterance perseverations. Results from this study highlight the need for future research to identify potential mechanisms influencing the presence of language perseverations and gaze avoidance.

Production of Verb Tense in Agrammatic Aphasia: A Meta-Analysis and Further Data.

In a majority of languages, the time of an event is expressed by marking tense on the verb. There is substantial evidence that the production of verb tense in sentences is more severely impaired than other functional categories in persons with agrammatic aphasia. The underlying source of this verb tense impairment is less clear, particularly in terms of the relative contribution of conceptual-semantic and processing demands. This study aimed to provide a more precise characterization of verb tense impairment by examining if there is dissociation within tenses (due to conceptual-semantic differences) and an effect of experimental task (mediated by processing limitations). Two sources of data were used: a meta-analysis of published research (which yielded 143 datasets) and new data from 16 persons with agrammatic aphasia. Tensed verbs were significantly more impaired than neutral (nonfinite) verbs, but there were no consistent differences between past, present, and future tenses. Overall, tense accuracy was mediated by task, such that picture description task was the most challenging, relative to sentence completion, sentence production priming, and grammaticality judgment. An interaction between task and tense revealed a past tense disadvantage for a sentence production priming task. These findings indicate that verb tense impairment is exacerbated by processing demands of the elicitation task and the conceptual-semantic differences between tenses are too subtle to show differential performance in agrammatism.

Polycationic glycosides.

Cationic lipids have long been known to serve as antibacterial and antifungal agents. Prior efforts with attachment of cationic lipids to carbohydrate-based surfaces have suggested the possibility that carbohydrate-attached cationic lipids might serve as antibacterial and antifungal pharmaceutical agents. Toward the understanding of this possibility, we have synthesized several series of cationic lipids attached to a variety of glycosides with the intent of generating antimicrobial agents that would meet the requirement for serving as a pharmaceutical agent, specifically that the agent be effective at a very low concentration as well as being biodegradable within the organism being treated. The initial results of our approach to this goal are presented.

Polycations. 17. Synthesis and properties of polycationic derivatives of carbohydrates.

In our continuing investigation of polycationic salts for purposes of antimicrobial action, ion-channel blocking, and construction of ionic liquids, we have prepared several series of polycationic salts derived from carbohydrate precursors. These salts are currently being investigated for optimal efficacy as antibacterials and antifungals, as well as for other applications. The syntheses of such series of salts are described here along with preliminary antibacterial testing results and a discussion of their properties indicating their potential utility for several purposes.

Polymorphisms in the pertussis toxin promoter in Bordetella bronchiseptica veterinary isolates from Argentina.

Five restriction patterns (including a novel one) could be defined by polymerase chain reaction-restriction fragment length polymorphism on the pertussis toxin (PT) promoter region in local veterinary isolates, suggesting that PT gene analysis is a potential molecular marker for Bordetella bronchiseptica detection and typing.