Risk patterns associated with transient hearing impairment and permanent hearing loss in infants born very preterm: A retrospective study.

AIM: To determine the risk patterns associated with transient hearing impairment (THI) and permanent hearing loss (PHL) of infants born very preterm who failed hearing screenings. METHOD: We enrolled 646 infants (347 males, 299 females) born at no more than 30 weeks' gestation between 2006 and 2020 who received auditory brainstem response screening at term-equivalent age. Audiological examinations of infants who failed the screening revealed THI, when hearing normalized, or PHL, defined as a persistent unilateral or bilateral hearing threshold above 20 dB. Principal component analysis (PCA) was used to characterize risk patterns. RESULTS: Among the 646 infants, 584 (90.4%) had normal hearing, 42 (6.5%) had THI, and 20 (3.1%) had PHL. Compared with the group with normal hearing, the THI and PHL groups had significantly higher rates of neurodevelopmental impairment at 24 months corrected age. PCA of risk patterns showed the THI group and especially the PHL group had more severe haemodynamic and respiratory instability. Moreover, severe intraventricular haemorrhage (IVH) was also a risk for PHL. Propensity score matching revealed an association of haemodynamic and respiratory instability with PHL. INTERPRETATION: In infants born preterm, the severity and duration of haemodynamic and respiratory instability are risk patterns for both THI and PHL; severe IVH is an additional risk for PHL. WHAT THIS PAPER ADDS: Neurodevelopmental delay was more common in infants born preterm who failed hearing screening. Principal component analysis revealed the risk patterns associated with hearing impairment. Haemodynamic-respiratory instability was associated with transient and permanent hearing impairment outcomes. Severe haemodynamic-respiratory instability and intraventricular haemorrhage was associated with permanent hearing loss.

Early-life respiratory trajectories and neurodevelopmental outcomes in infants born very and extremely preterm: A retrospective study.

AIM: To determine whether early-life respiratory trajectories are associated with neurodevelopmental impairment (NDI) in infants born very and extremely preterm. METHOD: The daily type of respiratory supports in the first 8 weeks after birth were analysed in 546 infants (285 males, 261 females; median gestational age = 28.0 weeks, interquartile range = 3 weeks), comprising 301 infants born very preterm (gestation = 28-30 weeks) and 245 infants born extremely preterm (gestation <28 weeks), who survived to discharge from 2004 to 2018 and received follow-up assessment by Bayley Scales of Infant and Toddler Development at a corrected age of 24 months. NDI included cognition or motor impairment, moderate and severe cerebral palsy, or visual and hearing impairment. RESULTS: Clustering analysis identified three respiratory patterns with increasing severity: improving; slowly improving; and delayed improvement. These were significantly associated with increasing rates of NDI in infants born very and extremely preterm and smaller head circumference in infants born extremely preterm (both p < 0.001). By day 28, the proportion of infants who were under different categories of ventilation support significantly differed according to the three trajectory groups in infants born very and extremely preterm (both p < 0.05). Models that included adverse respiratory trajectories demonstrated more negative impacts on neurodevelopment than those without. INTERPRETATION: An adverse early-life respiratory trajectory was associated with NDI at follow-up, especially in infants born extremely preterm, suggesting a lung-brain axis of preterm birth. WHAT THIS PAPER ADDS: Clustering analysis identified three respiratory trajectories with increasing severity in infants born preterm. Increasing severity of respiratory trajectories was associated with increasing rates of neurodevelopmental impairment. Adverse respiratory trajectories had a significantly negative impact on neurodevelopmental outcomes.

OBJETIVO: Determinar se as trajetórias respiratórias no início da vida estão associadas ao comprometimento do neurodesenvolvimento (CND) em bebês nascidos muito e extremamente prematuros. MÉTODOS: O tipo diário de suporte respiratório nas primeiras 8 semanas após o nascimento foi analisado em 546 bebês (285 meninos, 261 meninas; idade gestacional mediana = 28,0 semanas, intervalo interquartil = 3 semanas), compreendendo 301 bebês nascidos muito prematuros (gestação = 28-30 semanas) e 245 bebês nascidos extremamente prematuros (gestação < 28 semanas), que sobreviveram à alta entre 2004 e 2018 e receberam avaliação de seguimento por meio da Bayley Scales of Infant and Toddler Development na idade corrigida de 24 meses. O CND incluiu deficiência cognitiva ou motora, paralisia cerebral moderada e grave ou deficiência visual e auditiva. RESULTADOS: A análise de agrupamento identificou três padrões respiratórios com gravidade crescente: melhorando; melhorando lentamente; e melhora tardia. Estes foram significativamente associados com taxas crescentes de CND em bebês nascidos muito e extremamente prematuros e menor perímetro cefálico em bebês nascidos extremamente prematuros (ambos p < 0,001). No dia 28, a proporção de bebês que estavam sob diferentes categorias de suporte ventilatório diferiu significativamente de acordo com os três grupos de trajetória em bebês nascidos muito prematuros e extremamente prematuros (ambos p < 0,05). Os modelos que incluíram trajetórias respiratórias adversas demonstraram mais impactos negativos no neurodesenvolvimento do que aqueles sem. INTERPRETAÇÃO: Uma trajetória respiratória adversa no início da vida foi associada ao CND no seguimento, especialmente em bebês nascidos extremamente prematuros, sugerindo um eixo pulmão-cérebro de nascimento prematuro.

Effect of first-month head-size growth trajectory on cognitive outcomes in preterm infants.

BACKGROUND: To examine whether the patterns of head-size growth trajectory in the first month after birth are associated with different susceptibility to cognitive impairment outcomes at age 24 months. METHODS: This retrospective cohort study included 590 infants of very-preterm survivors born between 2001 and 2016 receiving neurodevelopmental assessment at age 24 months. 403 children were enrolled for analysis after excluding infants with small-for-gestational age and severe brain injury. The head circumference (HC) growth evaluated weekly in the first month after birth compared to the at-birth HC was analyzed using group-based trajectory modeling. Neurocognition outcomes were determined as normal, borderline delay, or impaired using the Bayley Scales of Infant Development. RESULTS: The HC growth dynamics in the first month after birth showed three trajectory patterns: delayed catch-up (31.5%), slow catch-up (54.0%), and fast catch-up (14.5%), which significantly corresponded to different rates of impaired cognition at 19.5%, 6.0%, and 8.5%, respectively (p < 0.001). While 60% of the fast catch-up group had normal cognition, only one-third of the delayed catch-up group showed normal cognition. Three neonatal risk factors, gestational age (p = 0.006), respiratory distress syndrome requiring surfactant therapy (p = 0.012), and hemodynamically significant patent ductus arteriosus requiring intervention (p = 0.047) significantly affected HC growth trajectory patterning that led to cognitive impairment outcomes at follow-up. CONCLUSION: Preterm infants with delayed catch-up of head-size growth in the first month of age is susceptible to cognitive impairment outcome.

Regiodivergent C-H Arylation of Triphenylene Derivatives Controlled by Electronic Effects of Diaryliodonium Salts.

A regiodivergent C-H arylation of triphenylene derivatives with diaryliodonium salts was developed. The regiodivergence was controlled by electronic effects of diaryliodonium salts. When the aryl(mesityl)iodonium salts bearing strong electron-donating groups at the para-position of aryl groups were used, the arylation reactions occurred ortho to amide groups. However, if the aryl(mesityl)iodonium salts bearing electron-withdrawing groups or weak electron-donating groups at the para-position of aryl groups were utilized, the arylation reactions occurred meta to amide groups.

Epilepsy occurrence after neonatal morbidities in very preterm infants.

OBJECTIVE: This study investigated the incidence of epilepsy and identified neonatal risk morbidities for epilepsy in children born extremely preterm. METHODS: Of the 806 very preterm infants (birth weight < 1500 g, gestational age < 32 weeks) who survived and were discharged from the four neonatal intensive care units in southern Taiwan between 2003 and 2012, 686 (85.1%) had longitudinal neurodevelopmental follow-up assessments up to 5 years of age. RESULTS: Among the 686 very preterm children, 19 (2.8%) exhibited epilepsy at a mean age of 19 ± 14 months. The incidence of epilepsy was highest among infants with neonatal seizure (33%), followed by cystic periventricular leukomalacia (cPVL, 27%), high-grade intraventricular hemorrhage (IVH, 21%), and necrotizing enterocolitis (NEC) stage III (20%). NEC stage III, neonatal seizure, high-grade IVH, and cPVL were also independent neonatal risk morbidities for epilepsy. Furthermore, the incidence of epilepsy was 21.6% in preterm children with significant neonatal brain injury (SNBI; ie, high-grade IVH and cPVL), but only 1% in preterm children without SNBI. Among preterm children with SNBI, neonatal seizure was higher in preterm children with epilepsy than in those without epilepsy (23.1% vs 2.1%, P = .03). Among preterm children without SNBI, NEC stage III was higher in preterm children with epilepsy than in those without epilepsy (33.3% vs 1.8%, P < .01). The preterm children with epilepsy were prone to have neurodevelopmental disability regardless of whether they had neonatal brain injury, and drug-resistant epilepsy (42%), particularly those with neonatal high-grade IVH. SIGNIFICANCE: There is an elevated incidence of epilepsy among very preterm children, and particularly those with significant brain injury and/or severe NEC during the neonatal period. Very preterm children with epilepsy are prone to have neurodevelopmental disability and drug-resistant epilepsy.

Co-phasing experiment of a segmented mirror using a combined broadband and two-wavelength algorithm.

In this paper, a broadband phasing algorithm is combined with a two-wavelength phasing algorithm to detect the piston error of a segmented mirror with the advantages of long range, high precision, and fast detection. Moreover, an active optics co-phasing experimental system of the segmented mirror is built to verify the algorithm's effectiveness. The segmented mirror consists of four hexagonal segments, with flat-to-flat lengths of 100 mm and radii of curvature of 2000 mm. First, a Shack-Hartmann sensor and piezoelectric actuators are used to finely co-focus the segmented mirror. Then, the broadband phasing algorithm is used to reduce the piston error of the segmented mirror to several micrometers. Finally, the two-wavelength phasing algorithm is used to reduce the piston error of the segmented mirror to zero. The experimental results show that the measurement accuracy is better than 26 nm, and the adjustment accuracy is approximately 55 nm, which demonstrates that the combined algorithm is valuable for segmented-mirror co-phasing measurement and adjustment.

Highly Segregated Lamello-Columnar Mesophase Organizations and Fast Charge Carrier Mobility in New Discotic Donor-Acceptor Triads.

Four new donor-acceptor triads (D-A-D) based on discotic and arylene mesogens have been synthesized by using Sonogashira coupling and cyclization reactions. This family of triads consists of two side-on pending triphenylene mesogens, acting as the electron-donating groups (D), laterally connected through short lipophilic spacers to a central perylenediimide (PI), benzo[ghi]perylenediimide (BI), or coronenediimide (CI) molecular unit, respectively, playing the role of the electron acceptor (A). All D-A-D triads self-organize to form a lamello-columnar oblique mesophase, with a highly segregated donor-acceptor (D-A) heterojunction organization, consequent to efficient molecular self-sorting. The structure consists in the regular alternation of two disrupted rows of triphenylene columns and a continuous row of diimine species. High-resolution STM images demonstrate that PI-TP2 forms stable 2D self-assembly nanostructures with some various degrees of regularity, whereas the other triads do not self-organize into ordered architectures. The electron-transport mobility of CI-TP2, measured by time-of-flight at 200 °C in the mesophase, is one order of magnitude higher than the hole mobility. By means of this specific molecular designing idea, we realized and demonstrated for the first time the so-called p-n heterojunction at the molecular level in which the electron-rich triphenylene columns act as the hole transient pathways, and the coronenediimide stacks form the electron-transport channels.

A convenient tandem one-pot synthesis of donor-acceptor-type triphenylene 2,3-dicarboxylic esters from diarylacetylene.

A tandem one-pot method for the direct synthesis of polysubstituted triphenylene 2,3-dicarboxylic esters with different substitution patterns was developed by enyne metathesis of diarylacetylene, followed by Diels-Alder, aromatization and a cyclization cascade.

Mesomorphism Modulation of Perfluorinated Janus Triphenylenes by Inhomogeneous Chain Substitution Patterns.

Two isomeric series of compounds with "inverted" chains' substitution patterns, 7,10-dialkoxy-1,2,3,4-tetrafluoro-6,11-dimethoxytriphenylene and 6,11-dialkoxy-1,2,3,4-tetrafluoro-7,10-dimethoxytriphenylene, labelled respectively p-TPFn and m-TPFn, and two non-fluorinated homologous isomers, 3,6-dibutoxy-2,7-dimethoxytriphenylene and 2,7-dibutoxy-3,6-dimethoxytriphenylene, p-TP4 and m-TP4, respectively, were synthesized in three steps and obtained in good yields by the efficient transition-metal-free, fluoroarene nucleophilic substitution via the reaction of appropriate 2,2'-dilithium biphenylenes with either perfluorobenzene, C6 F6 , to yield p-TPFn and m-TPFn, or o-difluorobenzene, C6 H4 F2 , for p-TP4 and m-TP4, respectively. The single-crystal structures of p-TPF4, m-TPF4 and p-TP4, unequivocally confirmed that the cyclization reactions occurred at the expected positions, and that the fluorinated molecules stack up into columns with short separation, a propitious situation for the emergence of columnar mesophases. The mesomorphous properties were found to be greatly affected by both chains' length and positional isomerism: a Colhex phase is found for p-TPF4 and m-TPF4, but mesomorphism vanishes in p-TPF6, and changes for the isomeric homologs m-TPFn, with the induction for n≥6 of a lamello-columnar phase, LamColrec . As expected, both non-fluorinated compounds are deprived of mesomorphism. These compounds emit blue-violet colour in solution, independently of the chains' substitution pattern, and the absolute fluorescence quantum yields can reach up to 46 %. In thin films, fluorescence is slightly redshifted.

Comparing fine motor performance among young children with autism spectrum disorder, intellectual disability, attention-deficit/hyperactivity disorder, and specific developmental disorder of motor function.

Objective: The acquisition of fine motor skills is considered to be a crucial developmental milestone throughout early childhood. This study aimed to investigate the fine motor performance of young children with different disability diagnoses. Methods: We enrolled a sample of 1,897 young children under the age of 6 years who were at risk of developmental delays and were identified by a transdisciplinary team. A series of standardized developmental assessments included the Bayley Scales of Infant Development-Third Edition, Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition, Peabody Developmental Motor Scale-Second Edition, and Movement Assessment Battery for Children-Second Edition were used. Retrospective chart reviews were conducted on all children to identify specific developmental disorders. The number of autism spectrum disorder (ASD), intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), comorbidity, motor dysfunction, and unspecified developmental delays (DD) were 363 (19.1%), 223 (11.8%), 234 (12.3%), 285 (15.0%), 128 (6.7%), and 590 (31.1%), respectively. Results: Young children with ID, comorbidity, and motor dysfunction demonstrated significant difficulty in performing manual dexterity and visual motor integration tasks and scored significantly lower in these areas than children with ASD, ADHD, and unspecified DD. In addition, fine motor performance was associated with cognitive ability in children with different disability diagnoses, indicating that young children showed better fine motor performance when they demonstrated better cognitive ability. Conclusion: Our findings support that differences in fine motor performance differ by disability type. Close links between fine motor performance and cognitive ability in children under the age of 6 years were seen in all disability types.

A boy with a progressive neurologic decline harboring two coexisting mutations in KMT2D and VPS13D.

INTRODUCTION: Kabuki syndrome (KS) and spinocerebellar ataxia (SCA) are both rare conditions with neurodevelopmental abnormalities. Approaching a patient with complex phenotypes and differentiating the role of mutations may be beneficial but challenging in predicting the disease prognosis. CASE PRESENTATION: A boy presented with progressive ataxia, developmental regression, and myoclonus since 4 years of age. Additional features included growth hormone deficiency, excessive body hair, dysmorphic facies, hypoparathyroidism, and bilateral sensorineural hearing impairment. Brain magnetic resonance imaging depicted T2-weighted hyperintensities over bilateral globus pallidus, thalamus, subcortical white matter, and brainstem. The results of tandem mass spectrometry, mitochondrial deletion, and mitochondrial DNA sequencing were inconclusive. Whole-exome sequencing (WES) on genomic DNA obtained from peripheral blood cells revealed a known pathogenic variant at KMT2D gene (c.5993A > G, p.Tyr1998Cys) related to KS and two compound heterozygous, likely pathogenic variants at VPS13D gene (c.908G > A, p.Arg303Gln and c.8561T > G, p.Leu2854Arg) related to autosomal recessive SCA type 4 (SCAR4). DISCUSSION: SCAR4 is mainly adult-onset, but a few pediatric cases have recently been reported with progressive gait instability and developmental delay. The VPS13D gene has been suggested to play a role in mitochondrial size, autophagy, and clearance, thus explaining the clinical and imaging phenotypes. CONCLUSION: Our case showed a rare co-existence of KS and SCAR4, highlighting the utility of WES in atypical cases that a single-gene disease cannot fully explain.

Enzyme replacement therapy for children with acid sphingomyelinase deficiency in the real world: A single center experience in Taiwan.

Background: Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disease with multi-systemic involvement, with no disease-modifying treatment available. Olipudase alfa is an investigational enzyme product developed to replace the deficient acid sphingomyelinase in ASMD patients. Several clinical trials have reported promising safety and efficacy results in adult and pediatric patients. However, no data have been reported outside of the clinical trial setting yet. This study aimed to evaluate major outcomes in pediatric chronic ASMD patients receiving olipudase alfa in the real-world setting. Materials and methods: Two children with type A/B (chronic neuropathic) ASMD have received olipudase alfa treatment since May 2021. Clinical parameters, including height, weight, complete blood count, liver function tests, lipid profiles, biomarkers, abdominal ultrasonography with shear wave elastography, chest computed tomography, nerve conduction studies, neurodevelopmental evaluations, and six-minute walk tests, were checked at baseline and every three to six months in the first year of enzyme replacement therapy (ERT) to assess its efficacy and safety. Results: The two patients in our study started olipudase alfa treatment at the age of 5 years and 8 months and 2 years and 6 months. During the first year of treatment, both patients saw a reduction in their hepatic and splenic volumes as well as liver stiffness. Height z-score, weight z-score, lipid profiles, biomarker levels, interstitial lung disease scores, and bone mineral densities also improved over time. The six-minute walk test showed a gradual increase in walking distance in both patients. There were no obvious improvements or deterioration in neurocognitive function and peripheral nerve conduction velocities after treatment. No severe infusion-associated reactions were noted during the first year of treatment. One patient had two episodes of transient but significantly elevated liver enzymes during the dose-escalation phase. The patient was asymptomatic, and the impaired liver function resolved spontaneously within two weeks. Conclusion: Our results provide real-world experience that olipudase alfa is safe and effective in improving major systemic clinical outcomes for pediatric chronic ASMD patients. Monitoring of liver stiffness by shear wave elastography is a noninvasive procedure that can monitor treatment efficacy during ERT.

Chromium-Catalyzed Defluorinative Reductive Coupling of Aldehydes with gem-Difluoroalkenes.

Herein, a mild and convenient defluorinative reductive cross coupling of gem-difluoroalkenes with aliphatic aldehydes has been developed to afford diverse silyl-protected ß-fluorinated allylic alcohols. The reaction is operationally simple and shows good functional group tolerance with moderate to excellent yields. The utility of this method is demonstrated by converting the products into various bioactive fluorinated compounds, showing its potential applications in drug discovery and biochemistry.

Anti-freezing dual-network hydrogels with high-strength, self-adhesive and strain-sensitive for flexible sensors.

Hydrogels as flexible sensor have attracted significant attention due to its conductivity, stretchability and flexibility. However, it is still a great challenge to prepare hydrogels that simultaneously possess high strength, anti-fatigue, self-adhesion, and anti-freezing. Herein, a multifunctional dual-network hydrogel was prepared by in situ polymerization of acrylic monomer in chitosan chains, and coordinated with aluminum chloride and glycerol. Based on chain entanglement, hydrogen bonding and coordination interactions, this dual-network hydrogel exhibited excellent mechanical properties, good fatigue resistance, and excellent adhesion performance. It can be used as a strain sensor for its stable conductivity and high sensitivity, which could monitor both large human motions and subtle motions. Due to the presence of glycerol, the hydrogel showed outstanding freezing resistance and still kept flexible and conductive even at low temperatures (-20 °C). This hydrogel can be applied as a flexible wearable sensor for monitoring human motion in extreme low-temperature condition.

Multiple domestications of Asian rice.

The origin of domesticated Asian rice (Oryza sativa L.) has been controversial for more than half a century. The debates have focused on two leading hypotheses: a single domestication event in China or multiple domestication events in geographically separate areas. These two hypotheses differ in their predicted history of genes/alleles selected during domestication. Here we amassed a dataset of 1,578 resequenced genomes, including an expanded sample of wild rice from throughout its geographic range. We identified 993 selected genes that generated phylogenetic trees on which japonica and indica formed a monophyletic group, suggesting that the domestication alleles of these genes originated only once in either japonica or indica. Importantly, the domestication alleles of most selected genes (~80%) stemmed from wild rice in China, but the domestication alleles of a substantial minority of selected genes (~20%) originated from wild rice in South and Southeast Asia, demonstrating separate domestication events of Asian rice.

Agreement Between Caregivers' Concerns of Children's Developmental Problems and Professional Identification in Taiwan.

Objective: Early detection of developmental delays relies on the accuracy of the caregivers' concerns of children's developmental problems. The aim of this study was to investigate the agreement between the caregivers' awareness of children's developmental problems and professional identification. Methods: Caregivers of 1,963 children (age range: 5-71 months; mean: 38.4 months) younger than 6 years old who were at risk of developmental delays and referred to the center for a comprehensive evaluation were enrolled in this study. Children were identified by a transdisciplinary team including a pediatric neurologist, a pediatric psychiatrist, two psychologists, two occupational therapists, two physical therapists, two speech therapists, a social worker, and a special instructor. A series of standardized developmental assessments were used to identify children with developmental delay. Retrospective chart reviews were conducted on all children to confirm specific developmental disorders. Results: The caregivers' initial concerns of cognitive, speech/language, emotional/behavioral, and motor and global development showed low agreement with the results of professional identification. The major disagreement was observed in the cognitive domain. Speech/language developmental concern was an important red-flag indicator of cognitive and emotional/behavioral developmental delays. The presence of intellectual disability, autism spectrum disorder, and attention deficit hyperactivity disorder was high in this study. When having caregivers' concerns about speech/language and emotional/behavioral development, the odds of children with autism spectrum disorder was 2.37 and 2.17 times greater than those without autism spectrum disorder, respectively. The presence of attention deficit hyperactivity disorder was significantly associated with concerns about cognitive and emotional/behavioral developmental delays. Child's age and mothers' level of education were significant indicators for detecting the child's developmental problems. Conclusion: It is recommended that assessing the cognitive developmental status is essential for all children in the identification process. Practitioners should not overlook caregivers' concern about speech/language and emotional/behavioral development. Transdisciplinary practitioners provide educational guidance to caregivers, especially in the domains of cognitive, speech/language, and emotional/behavioral development.

Novel Variations in the KDM5C Gene Causing X-Linked Intellectual Disability.

BACKGROUND AND OBJECTIVES: To investigate the pathogenicity of 2 novel KDM5C variations, report the clinical and neuroimaging findings, and review the available literature. METHODS: Physical examinations, structural neuroimaging studies, and exome sequence analysis were performed. KDM5C constructs were used to study the effect of the variations in transfected cells. RESULTS: We identified 2 novel variations c.2233C>G and c.3392_3393delAG in the KDM5C gene harboring from 2 Chinese families with X-linked intellectual disability (ID). The affected male patients exhibited severe ID, short stature, and facial dysmorphism. The 1 with c.3392_3393delAG additionally had epilepsy and autistic spectrum disorder (ASD). Transiently transfected mutant KDM5C constructs both reduced protein expression and stability and decreased histone demethylase activities in cells. Reviewing the available literature, we found that the associated ASD tended to occur in patients with variations near the C-terminus of KDM5C. DISCUSSION: We report the clinical, molecular genetic, and pathologic features in patients with novel variations of KDM5C. The variability of the clinical phenotype in addition to an ID may associate with altered particular parts of KDM5C.

Postnatal Serum Total Thyroxine Level Associated with Short- and Long-Term Anthropometric Outcomes in Very Preterm Infants.

Thyroxine (T4) importantly regulates the growth of newborns. Compared to fetuses with equivalent gestational ages, very preterm infants (VPIs) often experience relatively low thyroxinemia, with a normal thyroid-stimulating hormone (TSH) concentration < 10 µIU/mL. However, there is continued debate regarding postnatal thyroxine supplementation for VPIs with normal TSH and transitionally low thyroxinemia. Little research has explored the role of the postnatal total T4 (TT4) serum concentration on the growth of VPIs. In this study, we aim to clarify whether the postnatal thyroxine concentration is associated with the short- and long-term growth outcomes of VPIs. A total of 334 surviving VPIs in our previously reported cohort, born in the period August 2007−July 2016, were enrolled. The exposure variable was the postnatal TT4 concentration at 1 month old. The primary outcomes were body weight increments over 28 days after the screening and anthropometric outcomes at the corrected age of 24 months old. Infants with any hormonal replacement, severe brain injury, congenital anomaly, or cerebral palsy were excluded. In total, 290 (86.8%) VPIs were included for analysis. In the 28 days after thyroid function screening, the TT4 concentration was found to have a significant association with positive increments in body weight (mean increment: 25.7 g per 1 µg/dL; p < 0.001) and a positive body weight z-score (mean increment: 0.039 per 1 µg/dL; p = 0.037), determined by generalized estimating equation analysis. At the corrected age of 24 months old, a higher postnatal TT4 concentration was associated with a lower body mass index (mean coefficient: −0.136; 95% CI: −0.231 to −0.041, p = 0.005) and lower body mass index z-score (mean coefficient: −0.097; 95% CI: −0.170 to −0.024, p = 0.009). Infants with a TT4 concentration > 6.4 ug/dL had significantly lower odds of overweight status (odds ratio: 0.365; 95% CI: 0.177 to 0.754, p = 0.006). We conclude that the postnatal TT4 concentration is associated with a positive increment in body weight in the short term. At the same time, the postnatal TT4 concentration is associated with lower odds of overweight status after long-term follow-up.

Modular Synthesis of Enantioenriched α-Chiral Homoallylic Amidines Enabled by Relay Ir/Cu Catalysis.

The cascade of Ir-catalyzed enantioselective allylic amination and Cu-catalyzed alkyne-azide cycloaddition was designed for the asymmetric synthesis of homoallylic amidines. The nucleophilic addition of an in situ-generated enantioenriched tertiary allylamine to a ketenimine intermediate triggers a rapid and stereospecific zwitterionic aza-Claisen rearrangement in a 1,3-chiral transfer manner. The approach allows modular access to enantioenriched α-chiral homoallylic amidines in high yields with a high level of enantiomeric purity.

Comorbidities associated with genetic abnormalities in children with intellectual disability.

Intellectual disability (ID) has emerged as the commonest manifestation of underlying genomic abnormalities. Given that molecular genetic tests for diagnosis of ID usually require high costs and yield relatively low diagnostic rates, identification of additional phenotypes or comorbidities may increase the genetic diagnostic yield and are valuable clues for pediatricians in general practice. Here, we enrolled consecutively 61 children with unexplained moderate or severe ID and performed chromosomal microarray (CMA) and sequential whole-exome sequencing (WES) analysis on them. We identified 13 copy number variants in 12 probands and 24 variants in 25 probands, and the total diagnostic rate was 60.7%. The genetic abnormalities were commonly found in ID patients with movement disorder (100%) or with autistic spectrum disorder (ASD) (93.3%). Univariate analysis showed that ASD was the significant risk factor of genetic abnormality (P = 0.003; OR 14, 95% CI 1.7-115.4). At least 14 ID-ASD associated genes were identified, and the majority of ID-ASD associated genes (85.7%) were found to be expressed in the cerebellum based on database analysis. In conclusion, genetic testing on ID children, particularly in those with ASD is highly recommended. ID and ASD may share common cerebellar pathophysiology.