TCF7L2 acts as a molecular switch in midbrain to control mammal vocalization through a transcriptional repression mechanism

Vocalization is an essential medium for sexual and social signaling in birds and mammals. Periaqueductal gray (PAG) a conserved midbrain structure is believed to be responsible for innate vocalizations, but its molecular regulation remains largely unknown. Here, through a mouse forward genetic screening we identified one of the key Wnt/β-catenin effectors TCF7L2/TCF4 controls ultrasonic vocalization (USV) production and syllable complexity during maternal deprivation and sexual encounter. Expression of TCF7L2 in PAG excitatory neurons is necessary for the complex trait, while TCF7L2 loss reduces neuronal gene expressions and synaptic transmission in PAG. TCF7L2-mediated vocal control is independent of its β-catenin-binding domain but dependent of its DNA binding ability. Patient mutations associated with severe speech delay disrupt the transcriptional repression effect of TCF7L2, while mice carrying those mutations display severe USV impairments. Therefore, we conclude that TCF7L2 orchestrates gene expression in midbrain to control vocal production through a transcriptional repression mechanism.

Generasi Alpha: Dampak Penggunaan Gawai Selama Masa Pandemi Covid-19

Gadgets have become an important necessity in the digital age. This phenomenon not only occurs among adults but also in children. The youngest generation today is known as Gen A or Alpha generation. experts predict this generation is most familiar with technology, especially during the Covid-19 pandemic so it needs guidance from older people because children will not gain social-emotional abilities if only interact with the device. The purpose of this study is to explain the influence of devices used in the lives of the Alpha generation during the Covid-19 pandemic. Research methods use qualitative methods, with descriptive approaches and data collection methods of research libraries. Research shows that the challenges of educating children are becoming increasingly complicated, especially during the Covid-19 pandemic. 29% AUD in 2020 in Indonesia using gadgets. This is due to changes in learning methods that occur during pandemics, as well as parents who let children play with gadgets without proper control, then they experience addiction, thus affecting motor, cognitive, and psychological development, as well as creativity. Screen time excessive risk experiencing speech delay, disturbance, weakness social skill and even brain damage. On the other hand, gadgets have a positive impact such as adding science and entertainment. Parents play an important role in controlling children in the use of gadgets so that they avoid addiction to give birth to the golden generation in the future.

Parental Support for Speech Delay in Early Childhood in Kalisari Village, Natar District, South Lampung Regency

This study was aims to explore, describe, and analyze parent support for the speech delay early childhood. This study used to the qualitative method of the research subject is both parents of children who experience speech delay in Kalisari village. This study was used to three methods of data collection, namely observation, interviews, and documentation. The data analyze used to descriptive qualitative. Based on the results of the discussion that has been described it can be concluded that parent support that has been given to children who experience speech delay is informational support, assessment support, instrumental support, emotional social support, and real support. Of the five supports, the researchers concluded that the support often used by subjects was informational support, namely parents provided support through the provision of good advice and advice, giving instructions by installing pictures in the refrigerator so that the twins could understand the food taken and want to say food they took, and provided information by taking the twins for a walk to get a new vocabulary.

Plasma Phthalate Levels In Children With Speech Delay

Speech delay is one of the most common developmental problems. One of the risk factors may be the exposure to environmental chemicals. There is increased environmental exposure to phthalates, an endocrine-disrupting chemical. In this study, we aimed to determine the relationship of phthalates with speech delay. We included 50 children with isolated speech delay and 40 healthy children of similar age. Children were surveyed for risk factors for speech delay and phthalate exposure. Plasma di-(2-ethylhexyl) phthalate (DEHP), mono-(2-ethylhexyl) phthalate (MEHP) and dibutyl phthalate (DBP) levels were measured by high pressure liquid chromatography. The DEHP, MEHP and DBP levels in study and control groups were 0.377 [0.003 - 1.224] µg/ml, 0.212 [0.007 - 1.112] µg/ml (p = 0.033), 0.523 [0.031 - 2.477] µg/ml, 0.152 [0.239 - 2.129] µg/ml (p <0.001), and 0.395 [0.062 - 1.996] µg/ml, 0.270 [0.006 - 0.528] µg/ml (p = 0.004), respectively. Multiple linear regression analysis was used to adjust the association between the phthalate levels and factors differing between the two groups in terms of delayed speech risk factors. While there was no significant difference between the study and control groups in terms of DEHP level (p=0.233), the MEHP and DBP levels were found significantly higher in the study group (p<0,001). Conclusion: The statistically significant higher phthalate levels in those with speech delay indicate that these children are more exposed to phthalates and more epidemiological studies are needed to evaluate the association between phthalates and speech delay.

Kecakapan Hidup Anak Speech Delay Di Kabupaten Sragen

Abstrak: Penelitian ini bertujuan untuk mendiskripsikan kecakapan apa saja yang dimiliki oleh anak yang mengalami speech delay dan upaya apa saja pengembangan yang dilakukan oleh orang tua anak mereka. Subjek dalam penelitian ini ialah dua anak yang mengalami speech delay di Kabupaten Sragen. Penggunakan metode dalam penelitian ini yaitu kualitatif dengan pendekatan studi deskriptif. Dalam pengumpulan data peneliti menggunakan teknik observasi, wawancara dan dokumentasi. Teknik analisis data yang digunakan adalah model Miles and Huberman. Hasil penelitian ini adalah anak yang mengalami speech delay tipe ekspresif yang mendapatkan kasih sayang dari orang tua dengan porsi lebih mampu melakukan kegiatan makan, menyiapkan perlengkapan untuk makan, menulis, mewarnai, BAK dan BAB, berniaga, memperbaiki mainannya sendiri, berbagi mainan dan makanan, membersihkan lingkungan, mandi, serta menyapa temannya yang dilakukan secara mandiri. Hal tersebut diperkuat dengan pengembangan-pengembangan yang dilakukan oleh orang tua anak speech delay di setiap kali berkegiatan, yaitu: penekanan mengucapkan doa sebelum makan dan minum, doa naik kendaran, orang tua mengajari anak mereka secara kongkret urutan-urutan melakukan kegiatan memakai pakaian, mengajari urutan dalam mandi yang berguna untuk kehidupan kedepannya. Begitu juga dengan masyarakat yang berada di lingkungan dekat dengan anak speech delay(Significant other) melakukan hal yang demikian.

Xq21.1q21.31 Duplication in Two Male Siblings

Despite the increased use of array comparative genomic hybridisation, duplications of Xq remain rarely reported in the literature. Xq21.1q21.31 duplication has previously been reported only once in a boy with features of Prader Willi syndrome (PWS). We report 2 malesiblings with maternally inherited duplication of Xq21.1q21.31 who demonstrate a variable phenotype. The proband has Prader Willi-like features such as global developmental delay, autism, obesity, short hands, and small genitalia with a history of food seeking behaviour, while his younger brother has isolated speech delay with some autistic features under evaluation. Both siblings have features such as bitemporal narrowing and small hands. It is therefore likely that the phenotype of duplications in this region is broader than PWS phenocopy, and further cases would be required to elucidate this.

Phenotypic and molecular spectra of patients with switch/sucrose nonfermenting complex-related intellectual disability disorders in Korea

Background The switch/sucrose nonfermenting (SWI/SNF) complex is an adenosine triphosphate-dependent chromatin-remodeling complex associated with the regulation of DNA accessibility. Germline mutations in the components of the SWI/SNF complex are related to human developmental disorders, including the Coffin–Siris syndrome (CSS), Nicolaides–Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. These disorders are collectively referred to as SWI/SNF complex-related intellectual disability disorders (SSRIDDs). Methods Whole-exome sequencing was performed in 564 Korean patients with neurodevelopmental disorders. Twelve patients with SSRIDDs (2.1%) were identified and their medical records were retrospectively analyzed. Results ARID1B, found in eight patients, was the most frequently altered gene. Four patients harbored pathogenic variants in SMARCA4, SMARCB1, ARID2, and SMARCA2. Ten patients were diagnosed with CSS, and one patient without a typical phenotype was diagnosed with ARID1B-related nonsyndromic intellectual disability. Another patient harboring the SMARCA2 pathogenic variant was diagnosed with NCBRS. All pathogenic variants in ARID1B were truncating, whereas variants in SMARCA2, SMARCB1, and SMARCA4 were nontruncating (missense). Frequently observed phenotypes were thick eyebrows (10/12), hypertrichosis (8/12), coarse face (8/12), thick lips (8/12), and long eyelashes (8/12). Developmental delay was observed in all patients, and profound speech delay was also characteristic. Agenesis or hypoplasia of the corpus callosum was observed in half of the patients (6/12). Conclusions SSRIDDs have a broad disease spectrum, including NCBRS, CSS, and ARID1B-related nonsyndromic intellectual disability. Thus, SSRIDDs should be considered as a small but important cause of human developmental disorders.

Retrospective comparison of death or neurodevelopmental outcomes in extremely low birth weight preterm infants following different management options of haemodynamically significant patent ductus arteriosus

Background Optimal management of haemodynamically significant patent ductus arteriosus (HsPDA) in premature babies remains controversial. Our aim is to compare death and/or adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants with HsPDA who were managed with conservative [C], medical [M] and/or surgical [S] treatment, with secondary aim to examine short-term morbidities among [S] and [C] groups. The study also compared outcomes in very low birth weight (VLBW) infants with HsPDA and non-HsPDA. Methods A retrospective study of VLBW preterm infants born before 29 weeks in Singapore from 2007 to 2016 was conducted. Results A total of 474 VLBW infants were admitted in NUH from 2007 to 2016. Infants aged between 24 + 0 and 28 + 6 weeks of gestation, weighing ≤1500 g and diagnosed with patent ductus arteriosus (PDA) were included in the study, of which 172 infants (124 HsPDA and 48 non-HsPDA) were analyzed. Among infants with HsPDA, 17 infants were managed with [C], 83 with [M] and 24 with [S]. Mortality was not increased regardless of the presence of HsPDA or treatment received. Infants with non-HsPDA were less likely to have isolated speech delay (p < 0.05), but not global developmental delay (GDD). No significant differences in neurodevelopmental outcomes such as hearing loss, cerebral palsy (CP) and speech delay were found. [M + S] infants were at a higher risk of developing chronic lung disease (CLD) (OR 6.83, p < 0.05) and short-term growth failure compared to [C] infants. They were significantly shorter and had a smaller head circumference at discharge (p < 0.05). [M + S] infants also had elevated creatinine compared to those in group [C] (81.1 ± 24.1 vs 48.3 ± 11.8 umol/L, p < 0.000). Conclusions Compared to conservative management, infants requiring [M + S] treatment for HsPDA were more likely to have short-term complications such as CLD, elevated creatinine, and poorer growth. Despite a more turbulent postnatal course, death and/or adverse neurodevelopmental outcomes were not worse in infants managed with [M + S].