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1.
Int J Speech Lang Pathol ; : 1-15, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38764397

RESUMO

PURPOSE: A long-standing issue in identifying developmental language disorder (DLD) in multilingual children is differentiating between effects of language experience and genuine impairment when clinicians often lack suitable norm-referenced assessments. In this tutorial we demonstrate, via a case study, that it is feasible to identify DLD in a multilingual child using the CATALISE diagnostic criteria, Language Impairment Testing in Multilingual Settings (LITMUS) assessment tools, and telepractice. METHOD: This tutorial features a case study of one 6-year-old Urdu-Cantonese multilingual ethnic minority child, and seven age- and grade-matched multilinguals. They were tested via Zoom using Urdu versions of the Multilingual Assessment Instrument for Narratives (LITMUS-MAIN), the Crosslinguistic Lexical Task (LITMUS-CLT), the Crosslinguistic Nonword Repetition Test (LITMUS-CL-NWR), and the Sentence Repetition Task (LITMUS-SRep). RESULT: The child scored significantly lower in the LITMUS tests compared to her peers in her best/first language of Urdu. Together with the presence of negative functional impact and poor prognostic features, and absence of associated biomedical conditions, the findings suggest this participant could be identified as having DLD using the CATALISE diagnostic criteria. CONCLUSION: The result demonstrates the promise of this approach to collect reference data and identify DLD in multilingual children. The online LITMUS battery has the potential to support identification of multilingual DLD in any target language.

2.
J Speech Lang Hear Res ; 67(6): 1772-1784, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38683057

RESUMO

PURPOSE: Nonword repetition (NWR) has been described as a clinical marker of developmental language disorder (DLD), as NWR tasks consistently discriminate between DLD and typical development (TD) cross-linguistically, with Cantonese as the only reported exception. This study reexamines whether NWR is able to generate TD/DLD group differences in Cantonese-speaking children by reporting on a novel set of NWR stimuli that take into account factors known to affect NWR performance and group differentiation, including lexicality, sublexicality, length, and syllable complexity. METHOD: Sixteen Cantonese-speaking children with DLD and 16 age-matched children with TD repeated two sets of high-lexicality nonwords, where all constituent syllables are morphemic in Cantonese but meaningless when combined, and one set of low-lexicality nonwords, where all constituent syllables are nonmorphemic. Low-lexicality nonwords were further classified on sublexicality in terms of consonant-vowel (CV) combination attestedness (whether or not CV combinations in nonword syllables occur in real Cantonese words). RESULTS: Children with DLD scored significantly below their peers with TD. Effect sizes showed that high-lexicality nonwords and nonword syllables with attested CV combinations offered the greatest TD/DLD group differentiation. Nonword length and syllable complexity did not affect TD/DLD group differentiation. CONCLUSIONS: NWR can capture TD/DLD group differences in Cantonese-speaking children. Lexicality and sublexicality effects must be considered in designing NWR stimuli for TD/DLD group differentiation. Future studies should replicate the present study on a larger sample size and a younger population as well as examine the diagnostic accuracy of this NWR test. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25529371.


Assuntos
Transtornos do Desenvolvimento da Linguagem , Fonética , Humanos , Masculino , Feminino , Transtornos do Desenvolvimento da Linguagem/psicologia , Criança , Testes de Linguagem , Pré-Escolar , Linguagem Infantil , Idioma
3.
J Anxiety Disord ; 103: 102857, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38507961

RESUMO

Given the high rate of trauma exposure among the general population, it is important to delineate the risk factors for post-traumatic stress disorder (PTSD). While historically implicated in panic disorder, anxiety sensitivity is increasingly found to play a role in PTSD. The present review investigated the size of the relationship between anxiety sensitivity and PTSD symptoms among trauma exposed adults. A systematic search on multiple electronic databases (PTSDpubs, CINAHL, MEDLINE and PsycINFO) generated a total of 1025 records, among which 52 (n = 15173) met study inclusion criteria and were included in our random effects meta-analysis. Our results indicated a medium effect size (r = .46, 95% CI =.41,.50) for the relationship between anxiety sensitivity and PTSD symptoms. There was significant between-study heterogeneity. Furthermore, sub-group analyses revealed that study design (cross-sectional vs. longitudinal) may significantly moderate the association between anxiety sensitivity and PTSD severity. No moderation effect was found for assessment of PTSD through interview versus questionnaire, interpersonal versus non-interpersonal trauma, or low versus high study quality. Such patterns of results are consistent with cognitive models of PTSD. Clinical implications, strengths and limitations of the review were discussed.


Assuntos
Terapia Cognitivo-Comportamental , Transtornos de Estresse Pós-Traumáticos , Adulto , Humanos , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia , Terapia Cognitivo-Comportamental/métodos , Estudos Transversais , Transtornos de Ansiedade/psicologia , Ansiedade
4.
Brain Lang ; 251: 105404, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38513427

RESUMO

Procedural circuit Deficit Hypothesis (PDH) of Developmental Language Disorder (DLD) predicts problems with learning and retention of grammar. Twenty 7- to 9-year-old Cantonese-speaking children with DLD and their typically developing (TD) age peers participated in a syntactic priming task that was given in two sessions one week apart. Production of Indirect Object Relative Clause (IORC) was tested using a probe test before and after the priming task, and one week later. The study involved two cycles of learning and retention, and two levels of prior knowledge. Bayesian linear mixed effects modelling was used for data analysis. Children with DLD learned, and possibly retained, IORC less well than TD children after age, working memory and general grammatical knowledge were controlled for. No interaction effects were significant, meaning that cycle and prior knowledge affected both groups similarly in learning and retention. Results were discussed in relation to PDH and the Complementary Learning Systems Theory.


Assuntos
Transtornos do Desenvolvimento da Linguagem , Criança , Humanos , Recém-Nascido , Teorema de Bayes , Aprendizagem , Linguística , Memória de Curto Prazo , Testes de Linguagem
5.
Int Dent J ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38350801

RESUMO

OBJECTIVES: The aim of this research was to compare the penetration ability of calcium silicate-based sealers (iRoot SP and TotalFill BC HiFlow) and an epoxy resin-based sealer (AH Plus) into the lateral canals using the single-cone (SC) or continuous wave compaction (CW) obturation techniques. METHODS: Ninety single-rooted human teeth received canal instrumentation and diaphanisation before artificial lateral canals were created at 3 different root levels. The specimens were randomly allocated into 6 groups based on the combination of obturation technique and sealer used. Radiographic and photographic measurements evaluated the percentage of sealer penetration. Statistical analysis was performed to compare the penetration ability amongst different types of sealers, obturation methods, and root levels. RESULTS: Although TotalFill BC HiFlow sealer combined with the CW technique demonstrated greater sealer penetration at the coronal level (P < .05), the overall penetration ability of iRoot SP, TotalFill BC HiFlow, and AH Plus was not significantly different. The deepest sealer penetration was observed at the apical root level. CONCLUSIONS: All sealers showed similar penetration abilities into the lateral canals using the SC or CW techniques in vitro. Calcium silicate-based sealers have comparable penetration ability into lateral canals compared to epoxy resin-based sealers using SC or CW obturation techniques.

6.
J Speech Lang Hear Res ; 67(3): 782-801, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38354102

RESUMO

PURPOSE: The current study investigated English prosodic focus marking by autistic and typically developing (TD) Cantonese trilingual children, and examined the potential differences in this regard compared to native English-speaking children. METHOD: Forty-eight participants were recruited with 16 speakers for each of the three groups (Cantonese-speaking autistic [CASD], Cantonese-speaking TD [CTD], and English-speaking TD [ETD] children), and prompt questions were designed to elicit desired focus type (i.e., broad, narrow, and contrastive focus). Mean duration, mean fundamental frequency (F0), F0 range, mean intensity, and F0 curves were used as the acoustic correlates for linear mixed-effects model fitting and functional data analyses in relation to groups and focus conditions (i.e., broad, narrow, and contrastive pre-, on-, and post-focus). RESULTS: The CTD group had post-focus compression (PFC) patterns via reducing mean duration, narrowing F0 range, and lowering mean F0, F0 curve, and mean intensity for words under both narrow and contrastive post-focus conditions, while the CASD group only had shortened mean duration and lowered F0 curves. However, neither the CTD group nor CASD group showed much of on-focus expansion (OFE) patterns. The ETD group marked OFE by increasing mean duration, mean F0, mean intensity, and higher F0 curve for words under on-focus conditions. CONCLUSIONS: The CTD group utilized more acoustic cues than the CASD group when it comes to PFC. The ETD group differed from the CASD and CTD groups in the use of OFE. Furthermore, both the CASD and CTD groups showed positive first language transfer in the use of duration and intensity and, potentially, successful acquisition in the use of F0 for prosodic focus marking. Meanwhile, the differences in the use of OFE between the Cantonese-speaking and English-speaking groups, not PFC, might indicate that Cantonese-speaking children acquire PFC prior to OFE.


Assuntos
Transtorno do Espectro Autista , Criança , Humanos , Acústica da Fala , Medida da Produção da Fala , Idioma , Acústica
7.
Ann Biomed Eng ; 52(5): 1378-1392, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38407724

RESUMO

An in silico study is performed to investigate fluid dynamic effects of central venous catheter (CVC) placement within patient-specific cavo-atrial junctions. Prior studies show the CVC infusing a liquid, but this study focuses on the placement without any liquid emerging from the CVC. A 7 or 15-French double-lumen CVC is placed virtually in two patient-specific models; the CVC tip location is altered to understand its effect on the venous flow field. Results show that the CVC impact is trivial on flow in the superior vena cava when the catheter-to-vein ratio ranges from 0.15 to 0.33. Results further demonstrate that when the CVC tip is directly in the right atrium, flow vortices in the right atrium result in elevated wall shear stress near the tip hole. A recirculation region characterizes a spatially variable flow field inside the CVC side hole. Furthermore, flow stagnation is present near the internal side hole corners but an elevated wall shear stress near the curvature of the side hole's exit. These results suggest that optimal CVC tip location is within the superior vena cava, so as to lower the potential for platelet activation due to elevated shear stresses and that CVC geometry and location depth in the central vein significantly influences the local CVC fluid dynamics. A thrombosis model also shows thrombus formation at the side hole and tip hole. After modifying the catheter design, the hemodynamics change, which alter thrombus formation. Future studies are warranted to study CVC design and placement location in an effort to minimize CVC-induced thrombosis incidence.


Assuntos
Cateteres Venosos Centrais , Trombose , Humanos , Veia Cava Superior , Átrios do Coração , Hemodinâmica
8.
JACC Cardiovasc Imaging ; 17(2): 128-145, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37410010

RESUMO

BACKGROUND: Cardiac magnetic resonance (CMR) differentiates cardiac metastasis (CMET) and cardiac thrombus (CTHR) based on tissue characteristics stemming from vascularity on late gadolinium enhancement (LGE). Perfusion CMR can assess magnitude of vascularity; utility for cardiac masses (CMASS) is unknown. OBJECTIVES: This study sought to determine if perfusion CMR provides diagnostic and prognostic utility for CMASS beyond binary differentiation of CMET and CTHR. METHODS: The population comprised adult cancer patients with CMASS on CMR; CMET and CTHR were defined using LGE-CMR: CMASS+ patients were matched to CMASS- control subjects for cancer type/stage. First-pass perfusion CMR was interpreted visually and semiquantitatively for CMASS vascularity, including contrast enhancement ratio (CER) (plateau vs baseline) and contrast uptake rate (CUR) (slope). Follow-up was performed for all-cause mortality. RESULTS: A total of 462 cancer patients were studied, including patients with (CMET = 173, CTHR = 69) and without CMASS on LGE-CMR. On perfusion CMR, CER and CUR were higher within CMET vs CTHR (P < 0.001); CUR yielded better performance (AUC: 0.89-0.93) than CER (AUC: 0.66-0.72) (both P < 0.001) to differentiate LGE-CMR-evidenced CMET and CTHR, although both CUR (P = 0.10) and CER (P = 0.01) typically misclassified CMET with minimal enhancement. During follow-up, mortality among CMET patients was high but variable; 47% of patients were alive 1 year post-CMR. Patients with semiquantitative perfusion CMR-evidenced CMET had higher mortality than control subjects (HR: 1.42 [95% CI: 1.06-1.90]; P = 0.02), paralleling visual perfusion CMR (HR: 1.47 [95% CI: 1.12-1.94]; P = 0.006) and LGE-CMR (HR: 1.52 [95% CI: 1.16-2.00]; P = 0.003). Among patients with CMET on LGE-CMR, mortality was highest among patients (P = 0.002) with lesions in the bottom perfusion (CER) tertile, corresponding to low vascularity. Among CMET and cancer-matched control subjects, mortality was equivalent (P = NS) among patients with lesions in the upper CER tertile (corresponding to higher lesion vascularity). Conversely, patients with CMET in the middle (P = 0.03) and lowest (lowest vascularity) (P = 0.001) CER tertiles had increased mortality. CONCLUSIONS: Perfusion CMR yields prognostic utility that complements LGE-CMR: Among cancer patients with LGE-CMR defined CMET, mortality increases in proportion to magnitude of lesion hypoperfusion.


Assuntos
Meios de Contraste , Neoplasias Cardíacas , Humanos , Adulto , Prognóstico , Valor Preditivo dos Testes , Gadolínio , Neoplasias Cardíacas/diagnóstico por imagem , Espectroscopia de Ressonância Magnética , Perfusão , Medição de Risco , Imagem Cinética por Ressonância Magnética
9.
Res Sq ; 2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38077079

RESUMO

Background: The COVID-19 pandemic and rise in anti-Asian racism have had adverse mental health impacts in Asian communities. The lack of culturally-responsive and linguistically-accessible mental health trainings hinders access to mental health services for Asian populations. In this study, we assessed the mental health needs of Asian communities in Greater Boston and evaluated cultural responsiveness of the Mental Health First Aid (MHFA), a first-responder training teaching participants skills to recognize signs of mental health and substance use challenges, and how to appropriately respond. Methods: This community-based participatory research with the Boston Chinatown Neighborhood Center (BCNC), Asian Women For Health (AWFH), and the Addressing Disparities in Asian Populations through Translational Research (ADAPT) Coalition employed two phases. In phase 1, we conducted focus groups with BCNC and AWFH staff and peer educators to assess mental health priorities of Asian populations in Boston. Findings informed phase 2, which evaluated cultural responsiveness of the MHFA through pre- and post-training questionnaires and focus groups with community participants. The pre-training questionnaire asked about mental health needs and barriers, help-seeking behaviors, and literacy; and personal and Asian community stigma. The post-training questionnaire and focus group with community participants asked about cultural competence of MHFA training for Asian populations. Paired t-tests were used to evaluate questionnaire responses. Thematic analysis was used to analyze interviews. Results: In total, 10 staff/educators and 8 community members participated in focus groups. They identified common mental health needs and workforce and culturally-responsive community strategies to support persons with mental health issues. Twenty-four community participants completed pre- and post-training questionnaires. They reported the MHFA training reduced mental health care stigma and increased mental health literacy. Recommendations to increase cultural-responsiveness of the MHFA were to include mental health case studies common in Asian populations and provide the training in other languages (e.g., Chinese, Vietnamese). Conclusion: Cultural responsiveness of the MHFA for Asian populations could be improved with the inclusion of case studies specific to the Asian communities and accessibility of the training in other languages. Increasing the cultural relevance and language accessibility of these trainings could help reduce mental health stigma and gaps in mental health awareness and service utilization among Asian populations.

10.
PLoS One ; 18(11): e0288021, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37934774

RESUMO

Developmental Language Disorder (DLD), present in 2 out of every 30 children, affects primarily oral language abilities and development in the absence of associated biomedical conditions. We report the first experimental study that examines relative clause (RC) comprehension accuracy and processing (via looking preference) in Cantonese-speaking children with and without DLD, testing the predictions from competing domain-specific versus domain-general theoretical accounts. We compared children with DLD (N = 22) with their age-matched typically-developing (TD) children (AM-TD, N = 23) aged 6;6-9;7 and language-matched (and younger) TD children (YTD, N = 21) aged 4;7-7;6, using a referent selection task. Within-subject factors were: RC type (subject-RCs (SRCs) versus object-RCs (ORCs); relativizer (classifier (CL) versus relative marker ge3 RCs). Accuracy measures and looking preference to the target were analyzed using generalized linear mixed effects models. Results indicated Cantonese children with DLD scored significantly lower than their AM-TD peers in accuracy and processed RCs significantly slower than AM-TDs, but did not differ from the YTDs on either measure. Overall, while the results revealed evidence of a SRC advantage in the accuracy data, there was no indication of additional difficulty associated with ORCs in the eye-tracking data. All children showed a processing advantage for the frequent CL relativizer over the less frequent ge3 relativizer. These findings pose challenges to domain-specific representational deficit accounts of DLD, which primarily explain the disorder as a syntactic deficit, and are better explained by domain-general accounts that explain acquisition and processing as emergent properties of multiple converging linguistic and non-linguistic processes.


Assuntos
Compreensão , Transtornos do Desenvolvimento da Linguagem , Humanos , Criança , Idioma , Linguística , Cognição
11.
Folia Phoniatr Logop ; 75(6): 447-455, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37778339

RESUMO

BACKGROUND: The recent development of the Global TALES Protocol provides a unique opportunity to conduct systematic cross-linguistic and cross-cultural comparisons of children's personal narratives. This protocol contains 6 scripted prompts to elicit personal narratives in school-age children about times when they experienced feeling happy/excited, worried, annoyed, proud, being in a problem situation, something important. OBJECTIVES: The objectives of this study were to examine the topics of the children's narratives when they responded to the 6 prompts and draw comparisons with the topics of narratives spoken by children from 10 other countries speaking 8 other languages as described in the original feasibility paper. METHODS: We translated the Global TALES Protocol into Hindi and collected personal narratives of thirty Hindi-speaking children (aged 6-9 years), residing in Varanasi, Uttar Pradesh, India. All personal narrative samples were elicited in person and audio recorded for manual coding of the topics. RESULTS: Although we observed many similarities in the topics of children's personal narratives between this dataset and the dataset reported on in the initial feasibility study, we also documented some novel topics, such as "welcoming guests" in response to the "excited" prompt; "financial problems" in response to the "worried" prompt; "helping someone by actions or by advising someone morally" in response to the "problem" prompt; and "mishap/personal loss" and "exams" in response to the "important" prompt. CONCLUSION: Some of these novel topics likely reflected the Indian culture. Because our study involved a group of children who are linguistically and culturally different from previous studies using the Global TALES protocol and, at ages 6-9 years, slightly younger than the 10-year-olds in prior studies, this study adds to the evidence that the Global TALES protocol can be used to elicit personal narratives of children from diverse languages and cultures, as young as age 6.


Assuntos
Idioma , Narração , Humanos , Criança , Linguagem Infantil , Linguística , Índia
12.
Front Psychol ; 14: 1128976, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37404579

RESUMO

Phonetic entrainment is a phenomenon in which people adjust their phonetic features to approach those of their conversation partner. Individuals with Autism Spectrum Disorder (ASD) have been reported to show some deficits in entrainment during their interactions with human interlocutors, though deficits in terms of significant differences from typically developing (TD) controls were not always registered. One reason related to the inconsistencies of whether deficits are detected or not in autistic individuals is that the conversation partner's speech could hardly be controlled, and both the participants and the partners might be adjusting their phonetic features. The variabilities in the speech of conversation partners and various social traits exhibited might make the phonetic entrainment (if any) of the participants less detectable. In this study, we attempted to reduce the variability of the interlocutors by employing a social robot and having it do a goal-directed conversation task with children with and without ASD. Fourteen autistic children and 12 TD children participated the current study in their second language English. Results showed that autistic children showed comparable vowel formants and mean fundamental frequency (f0) entrainment as their TD peers, but they did not entrain their f0 range as the TD group did. These findings suggest that autistic children were capable of exhibiting phonetic entrainment behaviors similar to TD children in vowel formants and f0, particularly in a less complex situation where the speech features and social traits of the interlocutor were controlled. Furthermore, the utilization of a social robot may have increased the interest of these children in phonetic entrainment. On the other hand, entrainment of f0 range was more challenging for these autistic children even in a more controlled situation. This study demonstrates the viability and potential of using human-robot interactions as a novel method to evaluate abilities and deficits in phonetic entrainment in autistic children.

13.
Children (Basel) ; 10(4)2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37189965

RESUMO

In recent years, the sustainability crisis has raised interest in the concept of resilience, i.e., the capacity to persist, adapt, or transform in the face of change and challenge. However, to date, resilience has only been studied to a limited extent within early childhood education and care (ECEC). This paper reports on a study that used critical document analysis of national and international policies to explore if and how the concept of resilience within ECEC could contribute to sustainability in a world of rapid change. Five national and four international documents were analysed through the theoretical lenses of childism and place-based education. The results show that resilience is implicitly expressed in ECEC policies yet is rarely linked to sustainability issues. Instead, policies mainly limit resilience to the psychological dimension and the individual child. The conclusion is that ECEC is an apt context for supporting resilience in multiple ways. It suggests using a holistic understanding of resilience to advocate for ECEC policies that include diverse perspectives of families and local communities, incorporate indigenous voices, and recognise the interconnectedness between humans and the more-than-human world.

14.
Front Psychol ; 14: 924056, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36923152

RESUMO

Introduction: The ability to produce a well-structured, coherent and informative narrative requires the integration of lexical and grammatical skills at different levels of complexity. Investigating how narrative macrostructure competence is predicted by microstructural linguistic skills is conceptually enlightening; yet there have been very few, if any, studies documenting the associations between macrostructure and microstructure in both languages of the same bilinguals. In this paper we attempt to address this research gap and report on the first empirical study of Urdu-Cantonese bilingual children's narrative abilities, bringing in data from a new language pair that is currently understudied. Methods: Twenty-four bilinguals (mean age = 9.17 years) acquiring Urdu as first, family and heritage minority language, and Cantonese as second, school and majority language were assessed via Multilingual Assessment Instrument for Narratives (MAIN). We examined these children's macrostructural competence and its relations to microstructural skills in both languages (Urdu and Cantonese). Three macrostructure components were scored as response variables: Story Structure (SS), Story Complexity (SC), Internal State Terms (IST). Four microstructural measures were scored as predictor variables: number of different words (NDW), mean length of Communication Units (MLCU), proportion of grammatical Communication Units (Gproportion), proportion of correct connectives linking the major episodic elements (Cproportion). Results: In regression analyses, NDW emerged consistently as a positive predictor of SS, SC and IST in both languages. MLCU and NDW were positive predictors of SS in the stronger L1, but NDW was the only positive predictor of SS in L2. By contrast, NDW and an index of syntactic competence (MLCU in L1, but Cproportion in L2) were significant or close-to-significant positive predictors of SC in both languages. NDW was the only positive predictor of IST in both languages. These findings suggested that the relationships between narrative macrostructure and specific microstructural abilities could manifest both similarly and differently between L1 and L2. Discussion: We discuss the findings by considering the unique nature of each macrostructure component and how each component might be related to specific microstructural linguistic skills. We suggest directions for further research and discuss how the current findings bring deeper implications for educators and clinicians in assessment, pedagogy, and intervention.

15.
J Exp Med ; 220(3)2023 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-36534085

RESUMO

Late cardiac toxicity is a potentially lethal complication of cancer therapy, yet the pathogenic mechanism remains largely unknown, and few treatment options exist. Here we report DNA-damaging agents such as radiation and anthracycline chemotherapies inducing delayed cardiac inflammation following therapy due to activation of cGAS- and STING-dependent type I interferon signaling. Genetic ablation of cGAS-STING signaling in mice inhibits DNA damage-induced cardiac inflammation, rescues late cardiac functional decline, and prevents death from cardiac events. Treatment with a STING antagonist suppresses cardiac interferon signaling following DNA-damaging therapies and effectively mitigates cardiac toxicity. These results identify a therapeutically targetable, pathogenic mechanism for one of the most vexing treatment-related toxicities in cancer survivors.


Assuntos
Antineoplásicos , Cardiotoxicidade , Dano ao DNA , Neoplasias , Animais , Camundongos , Imunidade Inata , Inflamação , Neoplasias/tratamento farmacológico , Nucleotidiltransferases/genética , Antineoplásicos/efeitos adversos
16.
J Virol ; 96(2): e0106321, 2022 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-34669512

RESUMO

COVID-19 affects multiple organs. Clinical data from the Mount Sinai Health System show that substantial numbers of COVID-19 patients without prior heart disease develop cardiac dysfunction. How COVID-19 patients develop cardiac disease is not known. We integrated cell biological and physiological analyses of human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the presence of interleukins (ILs) with clinical findings related to laboratory values in COVID-19 patients to identify plausible mechanisms of cardiac disease in COVID-19 patients. We infected hiPSC-derived cardiomyocytes from healthy human subjects with SARS-CoV-2 in the absence and presence of IL-6 and IL-1ß. Infection resulted in increased numbers of multinucleated cells. Interleukin treatment and infection resulted in disorganization of myofibrils, extracellular release of troponin I, and reduced and erratic beating. Infection resulted in decreased expression of mRNA encoding key proteins of the cardiomyocyte contractile apparatus. Although interleukins did not increase the extent of infection, they increased the contractile dysfunction associated with viral infection of cardiomyocytes, resulting in cessation of beating. Clinical data from hospitalized patients from the Mount Sinai Health System show that a significant portion of COVID-19 patients without history of heart disease have elevated troponin and interleukin levels. A substantial subset of these patients showed reduced left ventricular function by echocardiography. Our laboratory observations, combined with the clinical data, indicate that direct effects on cardiomyocytes by interleukins and SARS-CoV-2 infection might underlie heart disease in COVID-19 patients. IMPORTANCE SARS-CoV-2 infects multiple organs, including the heart. Analyses of hospitalized patients show that a substantial number without prior indication of heart disease or comorbidities show significant injury to heart tissue, assessed by increased levels of troponin in blood. We studied the cell biological and physiological effects of virus infection of healthy human iPSC-derived cardiomyocytes in culture. Virus infection with interleukins disorganizes myofibrils, increases cell size and the numbers of multinucleated cells, and suppresses the expression of proteins of the contractile apparatus. Viral infection of cardiomyocytes in culture triggers release of troponin similar to elevation in levels of COVID-19 patients with heart disease. Viral infection in the presence of interleukins slows down and desynchronizes the beating of cardiomyocytes in culture. The cell-level physiological changes are similar to decreases in left ventricular ejection seen in imaging of patients' hearts. These observations suggest that direct injury to heart tissue by virus can be one underlying cause of heart disease in COVID-19.


Assuntos
COVID-19/imunologia , Células-Tronco Pluripotentes Induzidas , Interleucina-10/imunologia , Interleucina-1beta/imunologia , Interleucina-6/imunologia , Miócitos Cardíacos , Células Cultivadas , Humanos , Células-Tronco Pluripotentes Induzidas/imunologia , Células-Tronco Pluripotentes Induzidas/patologia , Células-Tronco Pluripotentes Induzidas/virologia , Miócitos Cardíacos/imunologia , Miócitos Cardíacos/patologia , Miócitos Cardíacos/virologia
17.
Front Psychol ; 13: 1059895, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36733853

RESUMO

Introduction: Studies have documented that child experiences such as external/environmental factors as well as internal factors jointly affect acquisition outcomes in child language. Thus far, the findings have been heavily skewed toward Indo-European languages and children in the Western, educated, industrialized, rich and democratic (WEIRD) societies. By contrast, this study features an understudied minority language Kam, and a group of so-called left-behind children in China growing up in a unique social-communicative environment. Methods: Fifty-five bilingual children aged 5-9 acquiring Kam as home language were assessed using the Multilingual Assessment Instrument for Narratives (LITMUS MAIN). Twenty-three "two parents-left" children (mean age = 6;8, range: 5;0-9;2) remained in rural areas while both parents went to cities for employment, and they were raised by their grandparents. Thirty-two were "one parent-left" peers (mean age = 7;3, range: 5;0-9;3) who also resided in rural areas but were raised by one parent. Oral narrative texts were analysed for macrostructure based on story structure (SS), story complexity (SC) and internal state terms (IS). The study examined whether and how narrative production is predicted by internal factors such as chronological age and linguistic proficiency of a child and an external factor such as left-behind experience. Four measures were scored as outcome measures: SS, SC, IS type, IS token. Four measures were taken as predictors: chronological age, left-behind experience, scores in a lexical production task, and scores in a sentence repetition task tapping expressive morphosyntactic competence. Results: Results showed that left-behind experience consistently predicted all four outcome measures, where the "two parents-left" children scored significantly lower than their "one parent-left" peers. Expressive vocabulary scores predicted three measures: SS, SC, and IS Token. Expressive morphosyntactic scores predicted SS and SC. Age, by contrast, did not predict any outcome measure. Discussion: These findings suggested that being left-behind by both parents may be a negative prognostic indicator for the development and maintenance of heritage language abilities in ethnic minority children. We further discussed the conceptual significance of what it means for a child to be left-behind, by relating to more basic external factors in language development, including caregiver educational level, and amount of home language and literacy support by the caretakers.

18.
J Cardiovasc Magn Reson ; 23(1): 42, 2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33814005

RESUMO

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is widely used to identify cardiac neoplasms, for which diagnosis is predicated on enhancement stemming from lesion vascularity: Impact of contrast-enhancement pattern on clinical outcomes is unknown. The objective of this study was to determine whether cardiac metastasis (CMET) enhancement pattern on LGE-CMR impacts prognosis, with focus on heterogeneous lesion enhancement as a marker of tumor avascularity. METHODS: Advanced (stage IV) systemic cancer patients with and without CMET matched (1:1) by cancer etiology underwent a standardized CMR protocol. CMET was identified via established LGE-CMR criteria based on lesion enhancement; enhancement pattern was further classified as heterogeneous (enhancing and non-enhancing components) or diffuse and assessed via quantitative (contrast-to-noise ratio (CNR); signal-to-noise ratio (SNR)) analyses. Embolic events and mortality were tested in relation to lesion location and contrast-enhancement pattern. RESULTS: 224 patients were studied, including 112 patients with CMET and unaffected (CMET -) controls matched for systemic cancer etiology/stage. CMET enhancement pattern varied (53% heterogeneous, 47% diffuse). Quantitative analyses were consistent with lesion classification; CNR was higher and SNR lower in heterogeneously enhancing CMET (p < 0.001)-paralleled by larger size based on linear dimensions (p < 0.05). Contrast-enhancement pattern did not vary based on lesion location (p = NS). Embolic events were similar between patients with diffuse and heterogeneous lesions (p = NS) but varied by location: Patients with right-sided lesions had threefold more pulmonary emboli (20% vs. 6%, p = 0.02); those with left-sided lesions had lower rates equivalent to controls (4% vs. 5%, p = 1.00). Mortality was higher among patients with CMET (hazard ratio [HR] = 1.64 [CI 1.17-2.29], p = 0.004) compared to controls, but varied by contrast-enhancement pattern: Diffusely enhancing CMET had equivalent mortality to controls (p = 0.21) whereas prognosis was worse with heterogeneous CMET (p = 0.005) and more strongly predicted by heterogeneous enhancement (HR = 1.97 [CI 1.23-3.15], p = 0.005) than lesion size (HR = 1.11 per 10 cm [CI 0.53-2.33], p = 0.79). CONCLUSIONS: Contrast-enhancement pattern and location of CMET on CMR impacts prognosis. Embolic events vary by CMET location, with likelihood of PE greatest with right-sided lesions. Heterogeneous enhancement-a marker of tumor avascularity on LGE-CMR-is a novel marker of increased mortality risk.


Assuntos
Meios de Contraste , Neoplasias Cardíacas/irrigação sanguínea , Neoplasias Cardíacas/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Meglumina , Células Neoplásicas Circulantes/patologia , Compostos Organometálicos , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Neoplasias Cardíacas/mortalidade , Neoplasias Cardíacas/secundário , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Cidade de Nova Iorque , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco
19.
Front Psychol ; 12: 679008, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35002822

RESUMO

Emergentist approaches to language acquisition identify a core role for language-specific experience and give primacy to other factors like function and domain-general learning mechanisms in syntactic development. This directly contrasts with a nativist structurally oriented approach, which predicts that grammatical development is guided by Universal Grammar and that structural factors constrain acquisition. Cantonese relative clauses (RCs) offer a good opportunity to test these perspectives because its typologically rare properties decouple the roles of frequency and complexity in subject- and object-RCs in a way not possible in European languages. Specifically, Cantonese object RCs of the classifier type are frequently attested in children's linguistic experience and are isomorphic to frequent and early-acquired simple SVO transitive clauses, but according to formal grammatical analyses Cantonese subject RCs are computationally less demanding to process. Thus, the two opposing theories make different predictions: the emergentist approach predicts a specific preference for object RCs of the classifier type, whereas the structurally oriented approach predicts a subject advantage. In the current study we revisited this issue. Eighty-seven monolingual Cantonese children aged between 3;2 and 3;11 (Mage: 3;6) participated in an elicited production task designed to elicit production of subject- and object- RCs. The children were very young and most of them produced only noun phrases when RCs were elicited. Those (nine children) who did produce RCs produced overwhelmingly more object RCs than subject RCs, even when animacy cues were controlled. The majority of object RCs produced were the frequent classifier-type RCs. The findings concur with our hypothesis from the emergentist perspectives that input frequency and formal and functional similarity to known structures guide acquisition.

20.
Front Psychol ; 11: 573780, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329217

RESUMO

This article introduces the LITMUS-MAIN (Language Impairment Testing in Multilingual Settings-MAIN) and motivates the adaptation of this instrument into Chinese languages and language pairs involving a Chinese language, namely Cantonese, Mandarin, Kam, Urdu. We propose that these new adapted protocols not only contribute to the theoretical discussion on story grammar and widen the evidential base of MAIN to include more languages in studying bilinguals, they also offer new methods of assessing language development in young children that have the potential to tease apart the effects of language impairment and bilingualism and improve the identification of Developmental Language Disorder. These new protocols are the first tools to be designed for the dual assessment of language skills in these particular languages, in particular narrative skills in bilingual children speaking these languages. By catering to under-researched languages and over-looked groups of bilingual children, these new tools could improve the clinical management for certain bilingual ethnic minority children such as Urdu-Cantonese and Kam-Mandarin bilinguals, as well as promote the study of these groups and their acquisition issues. Advances in understanding the theoretical and acquisition issues in childhood bilingualism can also be made possible using these new tools.

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