DLD is a potential therapeutic target for COVID-19 infection in diffuse large B-cell lymphoma patients.

Since the discovery of copper induces cell death(cuprotosis) in 2022, it has been one of the biggest research hotspots. cuprotosis related genes (CRGs) has been demonstrated to be a potential therapeutic target for cancer, however, the molecular mechanism of CRGs in coronavirus disease 2019 (COVID-19) infected in DLBCL patients has not been reported yet. Therefore, our research objective is first to elucidate the mechanism and role of CRGs in COVID-19. Secondly, we conducted univariate and multivariate analysis and machine learning to screen for CRGs with common expression differences in COVID-19 and DLBCL. Finally, the functional role and immune mechanism of genes in DLBCL were confirmed through cell experiments and immune analysis. The research results show that CRGs play an important role in the occurrence and development of COVID-19. Univariate analysis and machine learning confirm that dihydrolipoamide dehydrogenase (DLD) is the common key gene of COVID-19 and DLBCL. Inhibiting the expression of DLD can significantly inhibit the cycle progression and promote cell apoptosis of DLBCL cells and can target positive regulation of Lysine-specific demethylase 1 (LSD1, also known as KDM1A) to inhibit the proliferation of DLBCL cells and promote cell apoptosis. The immune analysis results show that high-expression of DLD may reduce T cell-mediated anti-tumor immunity by regulating immune infiltration of CD8 + T cells and positively regulating immune checkpoints LAG3 and CD276. Reducing the expression of DLD can effectively enhance T cell-mediated anti-tumor immunity, thereby clearing cancer cells and preventing cancer growth. In conclusion, DLD may be a potential therapeutic target for COVID-19 infection in DLBCL patients. Our research provides a theoretical basis for improving the clinical treatment of COVID-19 infection in DLBCL.

Collaborative working in speech and language therapy for children with DLD-What are parents' needs?

BACKGROUND: Collaborative practice between therapists and parents is a key element of family-centred care and is essential if we want to address family priorities and needs in interventions. However, collaborative practice is challenging for speech and language therapists (SLTs) and parents. To facilitate collaboration, collaborative practices need to be implemented into speech and language therapy for young children with developmental language disorders (DLD) and their families. Actual change and implementation of collaboration in practice will be successful only when it corresponds with patients' needs, in our case the needs of parents of young children with DLD. AIMS: To explore parents' needs in their collaboration with SLTs during therapy for their young child with DLD. METHODS & PROCEDURES: Parents of children with (a risk of) DLD in the age of 2-6 years were eligible for participation. We recruited parents via SLTs. Twelve parents of children with DLD participated in semi-structured interviews about their needs in collaboration with SLTs. We used a phenomenological approach focusing on parents' lived experiences. We transcribed the interviews verbatim. All interviews were read/listened to and discussed by our parent panel, multiple researchers and the interviewer. Two researchers independently analysed the data using the reflective thematic analysis of Braun and Clarke. OUTCOMES & RESULTS: The analysis of the interviews resulted in six themes: (1) knowing what to expect, (2) knowing how to contribute, (3) feeling capable of supporting the child, (4) trusting the therapist, (5) alignment with parents and children's needs, preferences and priorities and (6) time and space for asking questions and sharing information. CONCLUSIONS & IMPLICATIONS: Parents want SLTs to invest time in collaborating with them. Parents need SLTs to empower them to become a collaborative partner and enable them to support their child in daily life. Parents need knowledge about the therapy process and diagnosis and skills in how to support their child's language development. Also, they need emotional support to feel secure enough to support their child, to ask questions to therapists and to bring up their own thoughts and opinions in therapy. Parents' needs are in line with collaborative working as described in literature, which underlines the importance of implementing collaborative working in speech and language therapy for young children with DLD. WHAT THIS PAPER ADDS: What is already known on the subject Several reviews have explored parents' perspectives on speech and language therapy. Results reveal parents' experiences with speech and language therapy in general, and parents' perspectives on specific topics such as shared decision-making and parents/therapists roles in therapy. What this study adds This study adds insights into parents' needs to ensure collaboration with speech and language therapists (SLTs). Parents of young children with developmental language disorders (DLD) need SLTs to invest time to create optimal collaboration. It is important for parents to have enough knowledge about DLD and the SLT process, skills and confidence in how to support their child and opportunities to share thoughts and questions with SLTs. Our results underline the importance of parents being empowered by SLTs to become a collaborative partner. What are the clinical implications of this work? When children are referred to speech and language therapy, parents often venture into an unknown journey. They need support from SLTs to become a collaborative partner in speech and language therapy. Parents need SLTs to invest time in sharing knowledge, skills and power and align therapy to parents' and child's needs, preferences, priorities and expectations.

Speed of processing in Developmental Language Disorder (DLD): The case of real-time grammatical processing.

BACKGROUND: Developmental Language Disorder (DLD) impacts various aspects of children's language abilities, including the processing of inflectional morphology. Prior research suggests that children with DLD exhibit deficits in processing speed and sensitivity to grammatical inflections, yet the relationship between these deficits remains unclear. AIMS: This study aimed to investigate the relationship between processing speed and sensitivity to inflectional morphology in children with DLD, focusing on their real-time processing abilities in response to regular past tense, third person singular, and regular plural inflections at different rates of sentence articulation. METHOD: Eighteen children with DLD and 18 age-matched controls underwent word monitoring tasks that assessed sensitivity to grammaticality of inflections in sentences presented at normal and slow rates of articulation. RESULTS: At a normal rate of articulation, children with DLD demonstrated slower response times and reduced sensitivity to grammaticality across all inflections compared to controls. When the articulation rate was slowed, children with DLD showed improved sensitivity, particularly to regular plural and third person singular inflections, although deficits in processing the regular past tense persisted. CONCLUSIONS: The findings suggest a significant relationship between processing speed and inflectional morphology sensitivity in children with DLD. Slower articulation rates improved grammatical sensitivity for certain inflections, highlighting the potential of tailored interventions that consider processing speed limitations. Persistent difficulties with the regular past tense inflection indicate the need for targeted support for children with DLD in this area. WHAT THIS PAPER ADDS: What is already known on this subject Children with Developmental Language Disorder (DLD) have a wide range of language difficulties, but deficits in inflectional morphology are regarded as a 'hallmark' of the disorder. Children with DLD are also very likely to show deficits in speed of processing, although it is not known if a 'slowness to process' can causally explain the language difficulties these children experience. What this study adds to existing knowledge When grammatical sensitivity was measured using an online real-time task, children with DLD showed widespread inflectional deficits when sentences were spoken at a normal conversational rate. When sentence articulation rate was slowed down, children with DLD were faster, more accurate and more sensitive to the grammaticality of constructions. However, deficits in the regular past tense remained persistent, even in this slow-rate condition. What are the clinical implications of this work? This study has implications for clinical and educational practices that work with children with DLD to improve their language skills. The findings of this study show that when children with DLD are given more time to process incoming information, their grammatical skills significantly improve. This study also shows that deficits in the regular past tense are persistent, and children are likely need extensive and intensive support with this particular grammatical feature.

Exploring grammatical development in children aged 2;6 to 7: a novel approach using elicited production.

The assessment of children's grammatical skills is a crucial component of diagnosing language disorders. Elicited production is a commonly used method for obtaining data on a child's productive language abilities. We introduce a new instrument developed as part of the third edition of a standardised test battery for German. This instrument utilises elicited production, wherein participants describe coloured pictures depicting everyday situations, in order to generate four test scores: mean length of utterances, completeness of utterances, and two grammar scores comprising relevant target structures. The construction of the grammar scores was inspired by the Index of Productive Syntax (IPSyn), modified for German and computerised. The detailed results provide a comprehensive profile of a child's syntactic and morphological strengths and weaknesses. Analysis of data collected from 348 monolingual German children who formed part of the norming sample, aged between 2;6 and 6;11 years of age, revealed age-related changes in these scores. Additionally, the age range was determined for both grammatical milestones and 'red flags', which may indicate potential problems in language development. In conclusion, the newly developed, time-efficient instrument allows for a detailed assessment of grammatical skills, identification of potential intervention targets, and facilitates various research objectives.

The use of referring expressions in Mandarin-speaking children with and without developmental language disorder.

This study investigated the use of referring expressions in Mandarin-speaking children with and without developmental language disorder (DLD). The data consist of narratives elicited from 18 children with DLD and 18 typically-developing (TD) children matched on chronological age. Participants' referring expressions were analysed in terms of referential form, function, and adequacy. The overall results of form - function mappings showed that the two groups of children were quite similar in their referential choices, indicating that both groups were sensitive to function constraints and listener needs. On the other hand, children with DLD were less successful than TD children in producing adequate subsequent mentions, suggesting that referential adequacy would be useful for identifying areas of difficulty children with DLD would have in referencing.

Acquisition of Mandarin long passives by children with developmental language disorder.

This study investigated the comprehension and production of long passives (i.e. bei-constructions with an overt agent) in Mandarin-speaking children with developmental language disorder (DLD). Seventeen preschool children with DLD (1 female; mean age: 61 months old) and 23 typically developing (TD) children (6 females; mean age: 62 months old) participated in a sentence-picture matching task (for comprehension) and an elicited production task. Their nonverbal working memory (NVWM) was measured with the fourth edition of the Wechsler Preschool and Primary Scale of Intelligence. Results showed that children with DLD were less accurate and more likely to choose the picture with reversed thematic roles than their TD peers on passives in the sentence-picture matching task; in the elicited production task, they produced fewer target responses than TD children in passives. For NVWM, although that of the DLD group was lower than that of TD children, most children in the DLD group were within the average range. Furthermore, their performance on passives in the comprehension and production tasks was significantly correlated with their NVWM, which adds to the body of work suggesting links between complex syntax and working memory. However, the fact that NVWM could be preserved in the face of difficulties with passives suggests that this link may be due to NVWM enhancing performance during tasks with a high visual component, while it may not be underlyingly responsible for syntactic impairments in children with DLD.

A randomized study of parent- versus child-directed intervention for Dutch toddlers with DLD.

BACKGROUND: Indirect speech and language therapy, such as parent-implemented intervention, has been shown to be an effective approach for young children with speech and language disorders. However, relatively few studies have compared outcomes of parent-directed therapy with child-directed intervention, that is, individual therapy of a child delivered by a speech and language therapist (SLT). Although speech and language therapists (SLTs) regard parental engagement as imperative for successful intervention, currently they predominantly use child-directed intervention. AIM: To evaluate the effect of parent- versus child-directed speech-language therapy embedded in usual care intervention for young children with developmental language disorder (DLD). METHODS & PROCEDURES: In a randomized trial, forty-six 3-year-old monolingual children with DLD were assigned to parent-directed intervention or child-directed intervention groups. In addition, all children received usual care in special-language daycare centres. Outcomes included children's language development and functional communication, parents' language output, parents' perceptions and their self-efficacy. These were assessed at three time intervals, that is, at baseline, immediately after 6 months of treatment, and 1 year after baseline. The parent-directed intervention consisted of twelve 50-min sessions every 2 weeks with parent and child, consisting of parental training with immediate feedback by (SLTs. Children in the child-directed intervention group received individual speech-language therapy in weekly 30-min sessions for 6 months. OUTCOMES & RESULTS: Intervention in both groups was equally effective. All children improved significantly in receptive and expressive language measures as well as in functional communication at all intervals. All parents used significantly more language support strategies and were less concerned about their child's participation in communication. Parents in the parent-directed intervention group reported increased self-efficacy in stimulating their child's language development. In contrast, parents in the child-directed intervention group reported a decrease in self-efficacy. Though modest, these group differences were significant in both the short and long terms. Both parents and SLTs were positive about the parent-directed intervention. CONCLUSIONS & IMPLICATIONS: The effects of parent- and child-directed intervention for young children with DLD are similar. The parent-directed intervention adds to treatment options for parents as well as for SLTs and creates choices for shared decision-making. WHAT THIS PAPER ADDS: What is already known on the subject Language therapy for young children with DLD comprises various delivery models. Two of these are child- and parent-directed therapy by SLTs. Compared with no treatment, both delivery models are effective, but it is unclear if one of these results in better language outcomes than the other. SLTs value child-directed intervention more highly than indirect approaches where treatment is delivered by others. This study aims to compare the relative effectiveness of parent-directed intervention with child-directed intervention, both parts of multi-component usual care intervention. What this paper adds to existing knowledge This randomized trial indicates that a parent-directed intervention model is as effective as child-directed intervention by SLTs for children's language development and functional communication. Parents' use of language support strategies was also similar in both intervention models, in the short and long terms. Like in child-directed therapy, parent-directed intervention reduces parents' concerns. Contrary to child-directed treatment, parent-directed intervention increases parents' self-efficacy, that is, supporting their child's language development. What are the potential or actual clinical implications of this work? Though SLTs predominantly choose a child-directed intervention model, the study results show that they can consider parent-directed approaches too. There are no significant differences in children's language outcomes as a function of parent- or child-directed intervention. Furthermore, parents and SLTs were positive about the parent-directed intervention program and the SLTs evaluated it as valuable and feasible.

Creating the conditions for robust early language development for all: Part two: Evidence informed public health framework for child language in the early years.

BACKGROUND: One of the most significant developmental accomplishments is the emergence of language in early childhood. Whilst this process is effortless for most children, others can face significant hurdles. Identifying, in the early years, which children will go on to have developmental language disorder is, however, fraught with several well-documented challenges. In the preceding paper we described and linked new research evidence about factors that influence language development in the early years, noting that exposure to some may be time sensitive and that these influences cluster together and can accumulate over time. We demonstrated that risk profiles were associated with and characterised low language trajectories, and we considered how this information could be integrated into a concept that moves beyond screening at single time points in the early years. We argue that this evidence might be used to build an improved early years framework for language thereby creating a more equitable surveillance system that does not leave children living in less advantageous circumstances behind. Underpinning this thinking was a bioecological framework that incorporates the social, environmental and family factors in the child's ecosystem known to influence language development in the early years. AIMS: To develop a proposal for the design and implementation of an early language public health framework based on current best evidence METHODS: We synthesised the findings from the companion paper (Reilly & McKean 2023) regarding early language trajectories, inequalities and clustering of risks with key public health concepts, relevant intervention evidence and implementation theories to develop a new framework for language surveillance and preventative interventions in the early years. MAIN CONTRIBUTION: An evidence informed early language public health framework is presented. Describing in turn (1) essential components; (2) relevant interventions; (3) essential qualities for implementation ((i) probabilistic, (ii) proportionate, (iii) developmental and sustained and (iv) codesigned); (4) system-level structures and (5) processes required to adopt and embed an early language public health framework in an existing Local Government Area's child health surveillance and early prevention-intervention systems. CONCLUSIONS: Children's language development influences their life chances across the life course and language difficulties are unfairly distributed across society. Current evidence points to the need for whole systems approaches to early child language and enables a blueprint for such a framework to be described. WHAT THIS PAPER ADDS: What is already known on the subject Early child language development sets the stage for a child's life chances and language difficulties can have profound long-term consequences. Such difficulties are unfairly distributed across society and the reach of preventative services is not universal or equitable. WHAT THIS STUDY ADDS: Several effective primary and secondary preventative interventions exist but their successful implementation is not straightforward. An early language public health framework of surveillance and intervention is described to provide equitable and effective early interventions to children from 0-4 years. We detail the essential components, interventions and qualities of that framework and describe system-level structures and processes required to adopt and embed an early language public health framework in a given locality. WHAT ARE THE CLINICAL IMPLICATIONS OF THIS WORK?: A whole systems approach to early child language is required and should be co-designed through local collaboration with family, community and children's services stakeholders. A public health speech and language therapist role could catalyse the implementation of such approaches and support continuous improvement.

Language gains in 4-6-year-old children with developmental language disorder and the relation with language profile, severity, multilingualism and non-verbal cognition.

BACKGROUND: Early and effective treatment for children with developmental language disorder (DLD) is important. Although a growing body of research shows the effects of interventions at the group level, clinicians observe large individual differences in language growth, and differences in outcomes across language domains. A systematic understanding of how child characteristics contribute to changes in language skills is still lacking. AIMS: To assess changes in the language domains: expressive morphosyntax; receptive and expressive vocabulary; and comprehension, in children in special needs education for DLD. To explore if differences in language gains between children are related to child characteristics: language profile; severity of the disorder; being raised mono- or multilingually; and cognitive ability. METHODS & PROCEDURES: We extracted data from school records of 154 children (4-6 years old) in special needs education offering a language and communication-stimulating educational environment, including speech and language therapy. Changes in language were measured by comparing the scores on standardized language tests at the beginning and the end of a school year. Next, we related language change to language profile (receptive-expressive versus expressive-only disorders), severity (initial scores), growing up mono- and multilingually, and children's reported non-verbal IQ scores. OUTCOMES & RESULTS: Overall, the children showed significant improvements in expressive morphosyntax, expressive vocabulary and language comprehension. Baseline scores and gains were lowest for expressive morphosyntax. Differences in language gains between children with receptive-expressive disorders and expressive-only disorders were not significant. There was more improvement in children with lower initial scores. There were no differences between mono- and multilingual children, except for expressive vocabulary. There was no evidence of a relation between non-verbal IQ scores and language growth. CONCLUSIONS & IMPLICATIONS: Children with DLD in special needs education showed gains in language performance during one school year. There was, however, little change in morphosyntactic scores, which supports previous studies concluding that poor morphosyntax is a persistent characteristic of DLD. Our results indicate that it is important to include all children with DLD in intervention: children with receptive-expressive and expressive disorders; mono- and multilingual children, and children with high, average and low non-verbal IQ scores. We did not find negative relations between these child factors and changes in language skills. WHAT THIS PAPER ADDS: What is already known on the subject Intervention studies indicate that intervention can be effective, but not for all children with DLD, and not in all language domains. Longitudinal studies on language development show stable growth patterns in children with DLD at the group level. A systematic understanding of how child characteristics contribute to changes in language skills is still lacking. What this paper adds to existing knowledge In this study, we report on the language gains of a cohort of 154 children with DLD (4-6 years old), in a special education setting for children with language disorders. Our sample includes children with receptive-expressive disorders and expressive-only disorders, and monolingual as well as multilingual children. Our results show that children's language skills improved. The co-normed tests we used revealed that the children had much lower growth in morphosyntax than in the other language domains. Language gains between children with receptive-expressive and expressive-only language disorders did not differ, children with lower initial test scores showed more improvement than children with higher initial scores, multilingual children showed more gains in expressive vocabulary than monolingual children, and there was no effect of non-verbal IQ on change in language scores. What are the potential or actual clinical implications of this work? The results suggest that catching up on language is possible for children with DLD. It is important to include all children with DLD in intervention: mono- and multilingual children; children with receptive-expressive and expressive disorders; and children with high, average and low non-verbal IQ scores. We did not find negative relations between these child factors and changes in language skills. The limited growth in morphosyntax compared with other linguistic areas warrants the attention of both practitioners and researchers, with a particular focus on the implementation of research findings in clinical practice.

Transcriptome profiling and in silico docking analysis of phosphine resistance in rice weevil, Sitophilus oryzae (Coleoptera: Curculionidae).

The rice weevil, Sitophilus oryzae (Linnaeus, Coleoptera: Curculionidae), is a serious cosmopolitan pest that affects grain in storage and has developed high levels of resistance toward phosphine. In this study, RNA-seq data was used to study the phosphine resistance mechanisms in S. oryzae. Resistant and susceptible populations of S. oryzae were identified based on phosphine bioassays conducted in 32 populations collected across Tamil Nadu, India. Differential expression of mitochondrial (COX1, COX2, COX3, ND2, ND3, ATP6, and ATP8) and detoxification genes (Cyps, Gsts, and Cbe) were observed in the resistant and susceptible populations of S. oryzae. The previously characterized phosphine resistant gene, dld (dihydrolipoamide dehydrogenase) linked to the rph2 locus, was found to be up-regulated in resistant S. oryzae population (ISO-TNAU-RT) treated with phosphine. Also, the genes involved in Tricarboxylic acid (TCA) cycle were significantly down-regulated. In addition, a significant up-regulation in the expression of the antioxidant enzymes superoxide dismutase (2.5×) and catalase (2.1×) in ISO-TNAU-RT populations was recorded. Furthermore, a distinct amino acid substitution, Lysine > Glutamic acid (K141E) was identified in resistant phenotypes. In silico docking studies of both resistant and susceptible DLD protein with phosphine molecule revealed that the amino acid residues involved in the interaction were different. This suggested that the amino acid substitution might lead to structural modifications which reduces the affinity of the target (phosphine). This study provides insight on the various genes, pathways, and functional mechanisms having a significant role in phosphine resistance in S. oryzae.

Evaluation of the Cytotoxic, Antioxidative and Antimicrobial Effects of Dracocephalum moldavica L. Cultivars.

The aim of the present study was to correlate the antioxidant, antimicrobial, and cytotoxic activities of hydroalcoholic extracts obtained from the aerial parts of three Dracocephalum moldavica L. cultivars with their polyphenolic compositions. The polyphenols were identified and quantified using spectrophotometrical methods and LC-MS analysis. Their antioxidant capacities were assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods. Their in vitro antimicrobial efficacies were assessed using the agar well diffusion and broth microdilution methods. Their cytotoxicity was investigated on normal diploid foreskin fibroblasts (BJ) and on colorectal adenocarcinoma (DLD-1) cell lines. The results pointed out significant amounts of polyphenolic compounds in the compositions of the tested cultivars, with rosmarinic acid as the main compound (amounts ranging between 5.337 ± 0.0411 and 6.320 ± 0.0535 mg/mL). All three cultivars displayed significant antioxidant (IC50 ranging between 35.542 ± 0.043 and 40.901 ± 0.161 µg/mL for the DPPH assay, and for the FRAP assay 293.194 ± 0.213 and 330.165 ± 0.754 µmol Trolox equivalent/mg dry vegetal material) and antimicrobial potential (especially towards the Gram-positive bacteria), as well as a selective toxicity towards the tumoral line. A significant positive correlation was found between antioxidant activity and the total phenolic acids (r2 = 0.987) and polyphenols (r2 = 0.951). These findings bring further arguments for strongly considering D. moldavica cultivars as promising vegetal products, which warrants further investigation.

The contribution of visual and linguistic cues to the production of passives in ADHD and DLD: evidence from thematic priming.

This study investigated how thematic priming via visual and linguistic cues influences the choice of syntactic voice in healthy French-speaking adults and in French-speaking children with typical and atypical development. In particular, we focused on children with attention deficit hyperactivity disorder (ADHD) and developmental language disorder (DLD), two clinical groups with documented syntactic difficulties. Twenty adults (M= 24;7) and 60 children aged 6-11 (20 typically developing, 20 with DLD and 20 with ADHD) were presented with agent or patient cues that progressively increased in strength over three conditions: a no cue condition, a visual cue condition with two cue types (perceptual vs. referential) and a linguistic cue condition with two cue types (topicalization of the agent/patient with and without subsequent sentence initiation). Results showed that all participants produced more passives after having been presented with a patient cue, regardless of cue type (cue > no cue), but linguistic cues facilitated the production of passives significantly more than visual cues (linguistic cue > visual cue). We also found that children with DLD were more sensitive than children with ADHD to visual cues (DLD > ADHD), which were more implicit than the linguistic cues and may have required more attentional resources. The opposite pattern (ADHD > DLD) was true for the linguistic cues, which required syntactic processing. These findings highlight how the development of dynamic tools using cue modality and cue sensitivity might be useful for discriminating children with and without syntactic impairment.

Atypical phonological processes in naming errors of children with language impairment.

The current study explored the characteristics of phonological errors of preschool children with DLD (Developmental Language Disorder), distinguishing between typical versus atypical phonological processes in segmental, syllabic and word levels. The analysis included 87 responses of words with phonological errors from a naming test, produced by 13 preschool children with DLD, aged 4;4-6;3 years. These responses included 166 phonological processes, which were classified into typical and atypical processes at the levels of: segments, syllables, and prosodic words. The findings revealed that 70% of the phonological processes were atypical. Furthermore, ten children produced more atypical processes, and there were more atypical than typical processes in segmental and word levels. It is suggested that some children with DLD represent phonological processes that are similar to those that children with speech and sound disorders produce. Therefore, clinically, the results emphasise the importance of analysing the typical and atypical characteristics of phonological errors as part of language assessment.

Preferred argument structure in the oral narratives of adolescents with and without SLI.

According to the theory of 'Preferred Argument Structure' (PAS), the realisation and distribution of core arguments including the subject of a transitive verb (A), the direct object of a transitive verb (O) or the subject of an intransitive verb (S) in spoken discourse are subject to both grammatical and pragmatic constraints. However, previous studies on the formulation of argument structure have largely focused on the syntactic difficulties of children with SLI. In addition, little is known about the developmental outcomes in argument structure for adolescents with SLI. In this study, we compared PAS in the narratives of 19 adolescents with SLI (Mean age = 14.3; SD = 0.64) and 19 adolescents with typical language development (TLD; Mean age = 14.5; SD = 0.84). The core arguments of the predicate in each narrative based on the wordless picture storybook 'Frog, where are you?' were coded for grammatical roles (A, O and S), referential forms (lexical forms and non-lexical form including null and pronominal forms) and information status (given, accessible and new information). The data were then analysed for conformity to the grammatical and pragmatic constraints of the PAS theory. The two groups were found to be similar in their conformity to the pragmatic constraints but differed in how they conform to the syntactic constraints. In particular, the adolescents with SLI were more likely to produce clauses with two lexical arguments, and the lexical arguments occurred significantly more frequently at the subject role of a transitive verb than the TLD groups. Our results provide further evidence that it is a persistent grammatical deficit, rather than a pragmatic deficit, which poses a special challenge for adolescents with SLI in their formulation of argument structure in narratives.

A randomized phase 2 clinical trial of phentolamine mesylate eye drops in patients with severe night vision disturbances.

PURPOSE: Dim light vision disturbances (DLD) comprise a wide range of symptoms affecting the quality of vision at low illumination including glare, halos, and starbursts. This exploratory study investigated 1.0% phentolamine mesylate ophthalmic solution (PMOS) as a treatment to improve vision and image quality for patients with DLD. METHODS: In this placebo-controlled, randomized, double-masked clinical trial, 24 adult patients with severe DLD were randomized in a 2:1 ratio to receive either one dose of PMOS or placebo. Subjects were eligible if they reported experiencing severe night vision difficulty that was not eliminated by distance spectacle correction and scored ≥0.3 log units below the normal range of contrast sensitivity assessed under mesopic conditions with glare at ≥2 spatial frequencies. Key efficacy outcomes were change from baseline in pupil diameter, contrast sensitivity, and visual acuity. Safety measures including intraocular pressure, conjunctival hyperemia, and systemic effects were also assessed. RESULTS: Eight subjects were randomized to placebo (63% female; mean age 47 years) and 16 were randomized to PMOS (75% female; mean age 42 years). Mean (SD) pupil diameter of PMOS-treated subjects decreased significantly - 1.3 mm (0 to - 2.8 mm) with p < 0.0001. Mean contrast sensitivity with glare in PMOS-treated subjects improved significantly post-treatment at spatial frequencies 3, 6, 12, and 18 cycles per degree (p ≤ 0.03). PMOS also demonstrated improvements in the numbers of letters read for mesopic and photopic, high- and low-contrast visual acuity (LCVA). Importantly, a statistically greater proportion of PMOS-treated eyes registered mesopic LCVA 5 letter (69% vs. 31%, p = 0.029) and 10 letter (34% vs. 6%, p = 0.04) improvement, with a trend at 15 letters (19% vs. 0%, p = 0.16). PMOS was well tolerated with the only reported side effect being a mild increase in conjunctival hyperemia. CONCLUSION: PMOS was well tolerated and effectively reduced pupil size with improvements in contrast sensitivity and visual acuity in adults with severe DLD. Future Phase 3 studies should be conducted to further evaluate its potential to treat DLD. TRIAL REGISTRATION: The trial registration number is NCT04004507 (02/07/2019). Retrospectively registered.

Interventions for pre-school children with co-occurring phonological speech sound disorder and expressive language difficulties: A scoping review.

BACKGROUND: Recent evidence suggests that pre-school children with co-occurring phonological speech sound disorder (SSD) and expressive language difficulties are at a higher risk of ongoing communication and literacy needs in comparison with children with these difficulties in isolation. However, to date there has been no systematic or scoping review of the literature specific to interventions for children with this dual profile. AIMS: To explore the evidence regarding interventions for pre-school children with co-occurring phonological SSD and expressive language difficulties, including the content/delivery of such interventions, areas of speech and language targeted, and a broad overview of study quality. METHODS & PROCEDURES: A scoping review methodology was used in accordance with the guidance from the Joanna Briggs Institute. Following a systematic search of Ovid Medline, Ovid Emcare, OVID Embase, CINAHL, Psychinfo and ERIC, 11 studies were included in the review. A researcher-developed data extraction form was used to extract specific information about each intervention, with the JBI appraisal tools used to provide a broad overview of the quality of each study. MAIN CONTRIBUTION: Included papers consisted of six randomized controlled trials (RCTs), two cohort studies, two case studies and one case series. Interventions fell into two main categories: (1) integrated interventions that combined content for both speech and language targets and/or explicitly used the same type of technique to improve both domains; and (2) single-domain interventions that explicitly included content to target speech or language only, but also aimed to improve the other domain indirectly. Study quality varied, with detail on the content, context and delivery of interventions often underspecified, hampering the replication and clinical applicability of findings. CONCLUSIONS & IMPLICATIONS: Early emerging evidence was identified to support both integrated speech and language interventions as well as single-domain interventions. However, caution should be exercised due to the variation in the quality and level of detail reported for the interventions. Future intervention studies may seek to address this by reporting in accordance with Template for Intervention Description and Replication (TIDieR) reporting guidelines. This approach would enable clinicians to consider the applicability of the intervention to individual children within differing settings. WHAT THIS PAPER ADDS: What is already known on the subject Pre-school children with co-occurring phonological SSD and expressive language difficulties frequently present within speech and language therapy services. These children are at a higher risk of long-term communication and literacy difficulties compared with children with these needs in isolation. Some emerging evidence suggests that interventions for children with this co-occurring profile may exist within the literature; however, this evidence may not be known to clinicians in everyday practice. What this paper adds to existing knowledge This review is the first to systematically examine evidence of interventions for pre-school children with co-occurring phonological SSD and expressive language difficulties. The review identified a small number of intervention studies that varied in research quality and level of detail provided regarding the content and delivery of interventions. What are the potential or actual clinical implications of this work? The findings of this study highlight published evidence for interventions for pre-school children with co-occurring phonological SSD and expressive language difficulties. These may take the form of integrating techniques for speech/language into a single intervention, or the explicit targeting of one domain with the aim of also influencing the other. However, there is a need for further high-quality research in this area. Such studies should provide sufficient detail to enable replication. This would enable clinicians to understand the relevance and applicability of such intervention findings to the individual children they see within their clinical practice.

Chemical Composition Analysis, Cytotoxic, Antimicrobial and Antioxidant Activities of Physalis angulata L.: A Comparative Study of Leaves and Fruit.

Physalis angulata L. belongs to the family Solanaceae and is distributed throughout the tropical and subtropical regions. Physalis angulata leaf and fruit extracts were assessed for in vitro anticancer, antioxidant activity, and total phenolic and flavonoid content. The GC-MS technique investigated the chemical composition and structure of bioactive chemicals reported in extracts. The anticancer activity results revealed a decrease in the percentage of anticancer cells' viability in a concentration- and time-dependent way. We also noticed morphological alterations in the cells, which we believe are related to Physalis angulata extracts. Under light microscopy, we observed that as the concentration of ethanolic extract (fruit and leaves) treated HeLa cells increased, the number of cells began to decrease.

When Developmental Language Disorder Meets Diglossia: A Cross-Sectional Investigation of Listening Comprehension Among Native Arabic-Speaking Preschoolers.

Diglossia in the Arabic language refers to the existence of two varieties of the same language: the Spoken Arabic (SA) and the Literary Arabic (LA). This study examined the development of listening comprehension (LC) among diglossic Arabic K1-K3. For this purpose, a large sample of typically developing (TD; N = 210) and developmental language disorder children (DLD; N = 118) were examined using SA and LA texts. The analysis of variance conducted on their performance in LC revealed significant effects of K-level, group (TD vs. DLD) and text affiliation (SA vs. LA): higher scores in TD and in SA. A significant interaction between text affiliation and K-level was observed among the TD but not the DLD group. This interaction indicated that the gap in LC between the SA and LA varieties decreased with age only among TD children. The theoretical and pedagogical implications of these results are discussed.

Separation of circulating tumor cells from blood using dielectrophoretic DLD manipulation.

Circulating Tumor Cells (CTCs) play a prominent role in early cancer detection. Emerging label-free techniques can be promising to CTC detection due to advantages in preserving cell integrity and minimal sample consumption. Deterministic Lateral Displacement (DLD) is a size-based label-free technique employing laminar flow for continuous sorting of suspended cells. However, separation based solely on size is challenging as the size distributions of CTCs tend to overlap with blood cells. Moreover, the rarity of CTCs in blood requires high throughput processing of samples for clinical utility. In this work, a dielectrophoretic DLD technique is presented to segregate CTCs from blood. This technique utilizes the cell size and dielectric properties as well as particle movement caused by polarization effect to accomplish continuous separation at high flow rates. A numerical model is developed and validated to investigate the effects of various parameters related to the fluid flow, micro-post array, and electric field. It is demonstrated that the dielectrophoretic DLD with specific post arrangement can continuously separate A549 lung CTCs from WBCs by applying a field frequency close to the crossover frequency of CTCs. The analysis further indicates that such a device can perform well despite uncertainties of CTC crossover frequencies. Additionally, efficient separation with minimum clogging can be achieved by setting the electric field perpendicular to fluid flow. The presented platform offers distinct advantages and can be potentially combined with techniques such as antibody-based immune-binding methods for rapid detection of CTCs.

Does rhythmic priming improve grammatical processing in Hungarian-speaking children with and without developmental language disorder?

Research has described several features shared between musical rhythm and speech or language, and experimental studies consistently show associations between performance on tasks in the two domains as well as impaired rhythm processing in children with language disorders. Motivated by these results, in the current study our first aim was to explore whether a short exposure to a regular musical rhythm (i.e., rhythmic priming) can improve subsequent grammatical processing in preschool-aged Hungarian-speaking children with and without developmental language disorder (DLD). Second, we investigated whether rhythmic priming is specific to grammar processing by assessing priming in two additional domains: a linguistic but non-grammatical task (picture naming) and a non-linguistic task (nonverbal Stroop task). Third, to confirm that the rhythmic priming effect originates from the facilitating effect of the regular rhythm and not the negative effect of the control condition, we added a third condition, silence, for all the three tasks. Both groups of children showed better performance on the grammaticality judgment task in the regular compared to both the irregular and the silent conditions but no such effect appeared in the non-grammatical and non-linguistic tasks. These results suggest that (1) rhythmic priming can improve grammatical processing in Hungarian, a language with complex morphosyntax, both in children with and without DLD, (2) the effect is specific to grammar and (3) is a result of the facilitating effect of the regular rhythm. These results could motivate further research about integrating rhythmic priming into traditional speech-language therapy. A video abstract of this article can be viewed at https://youtu.be/zKzGuIjZyvU.