Developmental Age Research Articles

Familial dietary intervention in children with excess body weight and its impact on eating habits, anthropometric and biochemical parameters.

Obesity is considered a civilisation disease which increases mortality and impairs quality of life, also among children and adolescents. The prevalence of overweight and obesity is steadily increasing in the developmental age population. Environmental factors are responsible for the main reason of excessive adipose tissue accumulation. Among these, poor eating habits and lack of exercise play the largest role. Familial prevalence of obesity and family dietary patterns also receive significant attention. Many specialists believe that the treatment of obesity should be multidirectional, effective and minimally invasive. Therefore, effective and safe methods are being investigated to effectively reduce body weight and improve eating habits. Dietary education programmes are an alternative to improve the health status of obese and overweight children and adolescents. To be fully effective, these programmes should involve the whole family. In the face of constantly increasing prevalence of overweight and obesity in the developmental age population and the lack of effective methods to combat its occurrence, it seems appropriate to try to assess the effectiveness of a one-year-long dietary education of children and adolescents with excess body weight on their eating habits and the eating habits of their mothers, as well as selected anthropometric and biochemical parameters in these children using a simple educational tool, the Healthy Food Pyramid. The study group consisted of 68 children with overweight and obesity, patients of the Department of Paediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology of the Developmental Age of the Pomeranian Medical University in Szczecin. The study used a proprietary questionnaire to assess dietary habits. Patients participated in six individual educational meetings over a twelve-month period. Eating habits were assessed in children and mothers before and after dietary intervention. Sixty-seven questionnaires before and after the dietary intervention were used for analysis. Sixty-eight children completed the study. Those who did not complete the study came from families living in rural areas and their mothers mostly had primary or vocational education. One-year dietary education resulted in significant improvements in body weight, waist and hip circumference, WHtR and selected measured carbohydrate and lipid metabolism parameters with the exception of total cholesterol. The one-year dietary intervention did not have the same effect on the change in dietary habits in children and in their mothers.

A mixed-methods study into the effect of a psycho-educational programme for children with cerebral visual impairment (CVI)

Cerebral visual impairment (CVI) is one of the most common causes of visual impairment in children. CVI is a complex visual disorder to understand and explain to others. Understanding one’s diagnosis and being able to explain it to others may facilitate adaptive functioning. To educate children and young people on their CVI and accompanying needs, the computerized psycho-educational programme ‘My CVI’ has been developed. A mixed-methods study was conducted to evaluate the effect of this programme. The aims of the programme are to increase participants’ knowledge of CVI, as well as self-esteem (SDQ), adaptive coping (SCQ), and well-being (Cantril, PERIK, HRQoL). Thirty-nine children (aged 7–16 years; 51% boys) participated in a pre-test, post-test, and follow-up assessment. Qualitative interviews were conducted for a subjective evaluation of the programme. Participation in the psycho-educational programme resulted in increased knowledge of CVI, as well as a better teacher-reported social and academic self-concept and less self-reported feelings of social exclusion. No effects of participation were found on self-reported self-esteem, coping or other measures for well-being. An increase in knowledge of CVI was not associated with changes in psychosocial functioning. Qualitative data revealed that children enjoyed participating in the programme; they learned there are others with CVI, and gained more knowledge and practical tools on how to deal with their CVI. The results provide preliminary evidence that participation in the psycho-educational programme ‘My CVI’ increases children’s knowledge of their visual impairment as well as improves social outcomes and feelings of inclusion. The highest gains may be achieved through a personalized approach, depending on a child’s (developmental) age and parental involvement.

Abstract B024: Deconvolution by scRNAseq, scATACseq and functional genomics of impact of a relevant high risk diet on stem cells and homeostasis

Abstract Dietary patterns are major determinants of sporadic colon cancer incidence, the vast majority of the disease. NWD1 is a unique purified rodent diet that establishes mouse exposure to key nutrients recapitulating levels linked to higher risk in human, and is the only mouse model that develops sporadic intestinal and colon tumors, reflecting the etiology, incidence, frequency and lag with developmental age of the human disease. NWD1 fed mice reflect human metabolic syndrome with chronic inflammation, exhibit elevated Wnt signaling throughout the small and large intestinal mucosa and altered lineage marker expression, but Lgr5hi cells are suppressed in their lineage tracing, accumulation of mutations, and efficiency in tumor initiation. Alternate cells are mobilized to maintain the mucosa with increased efficiency to cause tumors. Deconvolving impact of NWD1 using scRNAseq, scATACseq and functional genomics provided novel insight into mechanisms elevating risk for sporadic tumors. NWD1 extensively, rapidly, and reversibly reprogrammed Lgr5hi stem cells, down-regulating Ppargc1a expression that altered mitochondrial structure and function and suppressed Oxphos and the TCA cycle. Ppargc1a genetic knockout in Lgr5hi cells recapitulated the dietary effects, and NWD1 or Ppargc1a inactivation repressed developmental maturation of Lgr5hi cell progeny as cells progressed through progenitor cell compartments. In compensation, mobilized Bmi1+, Ascl2hi cells maintained and adapted the mucosa. In parallel, NWD1 altered Ppargc1a chromatin structure in stem cells, and also for genes adapting enterocytes to the diet, independently confirming NWD1 epigenetic reprogramming of stem and differentiated cells. Importantly, pathways of antigen processing and presentation were elevated, especially in mature enterocytes, a pathogenic mechanism causing human chronic low-level pro-tumorigenic inflammation in IBD, also present in NWD1 fed mice. Fundamental conclusions: 1) plasticity of cells to function as stem cells mediates physiological adaptation of the mucosa. Thus, the human mucosa is in constant flux in response to its environment, supporting historic concepts of homeostasis by Claude Bernard and Walter Cannon as a continual process of tissue adaptation to its environment, not a single optimized state. 2) our data and the literature suggest that failure to recapitulate key human nutritional exposures contributes to why human stem cells reach crypt clonality in 6 years, 50-fold longer than the 6 weeks in the mouse. Thus, better modeling of human nutritional exposures in the mouse more accurately reflects human mechanisms of homeostasis and pathogenesis. 3) Complexity of cell reprogramming reported for the earliest premalignant human colon tumors is already present in the mucosa at nutritional risk for tumor development. 4) Oncogenic mutations provide a competitive advantage to intestinal stem cells in tumorigenesis, but the competition takes place on a playing field sculpted by the nutritional environment, a major determinant of who wins. Citation Format: Jiahn Choi, Xusheng Zhang, Wenge Li, Michele Houston, Karina Peregrina, Robert Dubin, Kenny Ye, Leonard H. Augenlicht. Deconvolution by scRNAseq, scATACseq and functional genomics of impact of a relevant high risk diet on stem cells and homeostasis [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr B024.

ISPAD Clinical Practice Consensus Guidelines 2022: Glycemic targets and glucose monitoring for children, adolescents, and young people with diabetes.

ISPAD Clinical Practice Consensus Guidelines 2022: Glycemic targets and glucose monitoring for children, adolescents, and young people with diabetes.

Anxiety symptoms among children visiting a pediatric emergency center in Qatar during the COVID-19 pandemic: A cross-sectional study.

Although the evidence base regarding the impact of the COVID-19 pandemic on children has been growing, descriptions of their experiences remain scarce. In this cross-sectional study, the authors used the Child-Reported Spence Children's Anxiety Scale to collect data from 91 children visiting a pediatric emergency center in Qatar during the pandemic. Around 25% of the children reported elevated levels of overall anxiety. Obsessive-compulsive symptoms were the most common, with 59.3% of children reporting elevated symptoms. The mean score of physical injury fears was significantly affected by gender, with females having higher scores. Overall rates for elevated anxiety symptoms were similar in natives and expatriate children. The findings suggest that the effects of the pandemic on children may depend on several vulnerability factors, including developmental age and gender. This study highlights the need to plan multidisciplinary strategies to enhance children's access to mental health services during and after the current health crisis.

Stimulate Smooth Motoric Development in Preschool Children By Using Educational Game Tools

Introduction: The development of smooth motoric, language, and interact to adapted in social are the growth of preschool aged children involves aggressive. Children’s movements that use a small muscles or only certain parts of the body smooth motoric is process in growth. The growth of this aspect can be stimulated, which kind of the use of Educational Game Tools (EGT). The purpose of this research was to identify the usefulness of using educational games equipment to stimulate smooth motoric growth in preschool children at Srikandi Kindergarten, Lhokseumawe.
 Methods: The method used in this research was Quasi-experimental Research. The technique of this study took the illustration by using the random sampling technique, with a total of 31 respondents who were given stimulation at that time. The data from this study were processed by using a dependent T-test of the variables of educational games and smooth motoric development in preschool children.
 Results: The results of this study showed that the use of educational games is effective for stimulating smooth motoric development in preschool children with a p-value = 0.000 < (0.05).
 Conclusion: The study can be concluded that children aged 4-5 years have questionable smooth motor development and irregularities before being given Educational Game Tools (EGT) stimulation. It is suggested to parents of respondents to use educational game tools to stimulate motoric development in children according to their developmental age.

Categorical perception of Mandarin lexical tones in language-delayed autistic children.

Some theories suggested that autistic people have better pitch perception skills than non-autistic people. However, in a context where pitch patterns are used to differentiate word meanings (i.e. lexical tones), autistic people may encounter difficulties, especially those with less language experience. We tested this by asking language-delayed autistic children to identify and discriminate two Mandarin lexical tones (/yi/ with Tone 1, meaning 'clothes'; /yi/ with Tone 2, meaning 'aunt'; /yi/: the standard romanization of Mandarin Chinese). On average, these autistic children were 7.35 years old, but their developmental age in language ability was 4.20, lagging behind 7-year-old non-autistic children in terms of language ability. Autistic children's performance in identifying and discriminating lexical tones was compared with two groups of non-autistic children: one group was matched with the autistic group on age, and the other was matched based on language ability. Autistic children performed differently from the non-autistic children matched on age, while autistic and non-autistic children matched on language ability exhibited seemingly similar performance. However, both the non-autistic groups have developed the perceptual ability to process lexical tones as different categories, but this ability was still developing in autistic children. Finally, we found autistic children who performed worse in identifying lexical tones had poorer language ability. The results suggest that language disability might have adverse influence on the development of skills of speech sound processing.

The Effectiveness of Different Training Methods in Soccer for Repeated Sprint Ability: A Brief Review

The purpose of this study was to systematically review the literature on the effect of exercise programs on the Repeated Sprint Ability (RSA) performance of soccer players. PubMed, Scopus and Google Scholar databases were searched for original research articles. The inclusion criteria for a study were to include different groups of intervention in soccer players and present the protocol’s characteristics and the study’s results. Twenty-one (21) studies met the criteria. For each study, the effect size (ES) and 95% confidential interval (CI) were calculated and evaluated as trivial, small, moderate or large. The results showed that in adults, the various programs showed from trivial (e.g., ES 0.185; 95% CI ± 0.089) to large beneficial effects (ES 2.92; 95% CI ± 0.29). At developmental ages, the beneficial effect was from trivial to moderate (ES 0.163; 95% CI ± 0.174, ES 0.787; 95% CI ± 0.074). Concerning the interventional programs, studies carried out by sprint and Small-Sided Games (SSG) interventions presented a large ES, while studies that carried out RSA exercises presented moderate ES. A variety of stimuli can improve the RSA performance of soccer players by causing trivial-to-large improvements. However, more effective are interventional exercises that include stimuli related to repeated sprint ability.

Optimising cutting method and timing for the control of Abutilon theophrasti seed production

AbstractAbutilon theophrasti (velvetleaf) is a widespread and problematic annual weed. Greenhouse and field experiments were conducted to investigate the effects of different cutting methods on the viability of A. theophrasti seeds. Three cutting methods were assessed: (1) Entire plant cut and dried (EPD)—plants were cut at soil level and dried with capsules attached on the greenhouse bench or soil surface for 4 weeks; (2) capsules detached and dried (CD)—capsules were removed from plants and dried for 4 weeks; and (3) capsules detached and tested while fresh (CF)—a control treatment. Before drying, the developmental stage (stage one, dark green; stage two, light green; stage three, yellowish‐green; or stage four, black with the slightly open capsule) and age (days after flowering, DAF) of each capsule was recorded. Seed viability was measured immediately in the CF treatment and after the 4‐week drying period in the EPD and CD treatments. No seeds in the EPD and CD treatments were viable when harvested at the first developmental stage (1–8 DAF) in either experiment, but 100% of seeds in the CF treatment in the field were viable when harvested at 8 DAF. In both greenhouse and field experiments, seeds attained full viability at earlier harvest ages in CF than in EPD or CD treatments, suggesting that seeds might become viable relatively early in development but lose viability if allowed to dry. These findings could be applied to optimise late‐season mechanical control of A. theophrasti.

Assessing the Attainment Rates of Updated CDC Milestones Using a New Israeli Developmental Scale.

Developmental milestones norms are widely used worldwide and are fundamental for early childhood developmental surveillance. We compared a new Israeli evidence-based national developmental scale with the recently updated Centers for Disease Control and Prevention (CDC) checklists. We used a cohort of nearly 4.5 million developmental assessments of 758 300 full-term born children aged 0 to 6 years (ALL-FT cohort), who visited maternal child health clinics in Israel for routine developmental surveillance. Among the assessed milestones of 4 developmental domains (gross motor, fine motor, language, and personal-social) we identified milestones that had equivalents on the CDC checklists and assessed the attainment rates of the Israeli children at the ages recommended by the CDC, at which ≥75% of the children would be expected to achieve the milestone. The analysis was repeated on a subgroup of 658 958 children who were considered healthy, typically developing by their birth and growth characteristics (NORMAL-FT cohort). There were 29 milestones, across all developmental domains and assessment ages, whose definitions by both tools were compatible, and could be compared. The attainment rate at the CDC-recommended age was >90% for 22 (76%) and 23 (79%) milestones, and the median attainment rates were 95.2% and 96.3% in the ALL-FT and NORMAL-FT cohorts, respectively. For almost all comparable milestones of all domains and all ages, children of the Israeli cohorts achieved the milestones earlier than expected by the CDC-defined threshold age. Evidence-based analysis of milestone norms among different populations may enable adjustments of developmental scales and facilitate more personalized developmental surveillance.

RJAfinder: An automated tool for quantification of responding to joint attention behaviors in autism spectrum disorder using eye tracking data.

Deficits in responding to joint attention (RJA) are early symptoms of autism spectrum disorder (ASD). Currently, no automated tools exist for identifying and quantifying RJA behaviors. A few eye tracking studies have investigated RJA in ASD children but have produced conflicting results. In addition, little is known about the trajectory of RJA development through developmental age. Here, a new video was designed including 12 clips of an actor pointing to or looking at an object. Eye tracking technology was used to monitor RJA in three groups: 143 ASD children assessed with the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) (4-7 years old), 113 age- and gender-matched typically developing children (TDC), and 43 typically developing adults (TDA) (19-32 years old). RJAfinder was developed in R and MATLAB to quantify RJA events from the eye tracking data. RJA events were compared among the three groups. Spearman correlation coefficients between total number of RJA events in ASD and the Social Responsiveness Scale (SRS) scores were calculated. A logistic regression model was built using the average valid sampling rate and the total number of RJA events as two predictive variables to classify ASD and TDC groups. ASD children displayed statistically significantly less RJA events than the TDC and TDA groups with medium-to-large-sized effects. ASD and TDC children both displayed more RJA events in response to pointing stimuli than to looking stimuli. Our logistic regression model predicted ASD tendency with 0.76 accuracy in the testing set. RJA ability improved more slowly between the ages of 4-7 years old in the ASD group than in the TDC group. In ASD children, RJA ability showed negative correlation with SRS total T-score as well as the scores of five subdomains. Our study provides an automated tool for quantifying RJA and insights for the study of RJA in ASD children, which may help improve ASD screening, subtyping, and behavior interventions.

Using a Humanized Animal Model to Determine the Minimum JAK2V617F Mutant Allele Burden Required to Generate MPN Pathologies

Myeloproliferative neoplasms (MPNs) are clonal hematological diseases driven by somatic mutations acquired in hematopoietic stem cells (HSCs) and characterized by the deviant, unregulated proliferation of one or more myeloid lineages. Chronic MPN can present as polycythemia vera (PV; excess erythrocytes), essential thrombocythemia (ET; excess platelets), or myelofibrosis (MF; bone marrow fibrosis). More than 300,000 patients are currently living with an MPN diagnosis in the United States. The JAK2V617F variant is an acquired somatic mutation recurrently found in MPN patients and is used as a diagnostic marker along with increased hematocrit, increased hemoglobin, and adverse thrombotic events. In MPN patients, the frequency of JAK2V617F mutant cells varies widely but is known to induce an MPN phenotype with both high (>50%) and very low (<5%) variant allelic frequency (VAF). The reason for this is currently unknown. Most JAK2-mutant animal models model a VAF which is much higher than the lower end of detectable VAFs found in MPN patients. This results in a very limited understanding of what the minimal mutant cell burden required for disease manifestation is. The understanding of genotype/phenotype relationships in patients with low JAK2V617F VAF chronic MPN is paramount to our understanding of this disease and its hematological progression. To this end, we have designed a clinically relevant, humanized mouse model wherein we employ CRISPR and homology directed repair (HDR) via a single stranded oligo donor nucleotide sequence (ssODN) to knock-in the JAK2V617Fmutation at the endogenous locus of human cells at low VAF. In addition, a synonymous JAK2V617V mutation was introduced via CRISPR/ssODN in parallel cells to serve as a control tracked by VAF alongside the VAF of JAK2V617F in their corresponding cohorts. The respective ssODNs were nucleofected into either umbilical cord blood (UCB) derived CD34+ cells or healthy adult bone marrow (BM) derived CD34+ cells to investigate the possibility that developmental age is a variable in low JAK2V617F VAF inducing a clinical MPN phenotype. After nucleofection, 20,000 CD34+ cells were intra-tibially transplanted into sub-lethally irradiated (250 rads) NSGS mice. The low cell input was utilized to limit engraftment and initial disease burden of mutant cells. Effect was measured by mutant allele burden by droplet-digital PCR (ddPCR) analysis, flow cytometry at selected timepoints to track human cell engraftment, spleen weight, and complete blood count (CBC) analysis including hematocrit, hemoglobin, white blood cells, and platelets. At 4 months post-transplant, peripheral blood hCD45+ engraftment across all cohorts averaged less than 3%. Average VAF of circulating hCD45+ cells increased in both JAK2V617F cohorts 5 months post-transplant compared to day 0 post nucleofection. Notably, overall JAK2V617F VAF in each sample remained <5% when adjusted to include both human and mouse derived peripheral blood cells. Remarkably, both hematocrit (p= .037 in UCB cohorts and p=.0096 in BM cohorts; Figure 1A) and hemoglobin (p=.046 in UCB cohorts and p=.0026 in BM cohorts; Figure 1B) were significantly elevated in both JAK2V617F cohorts compared to their respective JAK2V617V controls, while white blood cell and platelet counts remained unchanged within normal ranges. In addition, spleen weights were significantly increased in both JAK2V617F cohorts compared to their respective controls. These data demonstrate a successful clinical model of MPN which induces a classical MPN phenotype where a low VAF of JAK2V617F corresponds with a significant increase of hematocrit, hemoglobin, and spleen weight in a humanized mouse model compared to relevant controls. In addition, we demonstrate that while engraftment due to low hCD34+ cell input remains low after 4 months, the VAF of JAK2V617F within the hCD45+ sub- population increases. This successfully enables the overall VAF contributing to the MPN phenotype to remain at clinically relevant lower levels compared to other models with much higher VAF contributions. We believe this model to be of high clinical relevance into the investigation of how low JAK2V617F burden relates to disease development and progression in MPN patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Engagement of Preschool-Aged Children in Daily Routines.

Child engagement refers to the time spent interacting with physical and social environments according to age, abilities, and a situation. The aim of this study is to assess the functioning of children in early childhood routines using engagement assessment instruments relative to the presence of developmental disabilities, age, gender, and parental characteristics within the contexts of preschool and family routines. The sample comprised 150 children aged 3-5 (AS = 4.02, D = 0.78), including typically developing children (N = 49) and children with developmental disabilities (N = 101). To assess the children's engagement in preschool classrooms, we used the Classroom Measure of Engagement, Independence, and Social Relationships (ClaMEISR), and the Child Engagement in Daily Life Measure was used to assess the children's engagement in family routines. The results obtained indicate a significantly higher rate of engagement in routines and activities among girls and older children. Parental characteristics associated with children's engagement included employment and marital status. Children with developmental disabilities, compared to their typically developing peers, had lower levels of engagement in social relationships and functional independence in daily routines. The results indicate that both instruments have a high internal consistency and are thus suitable for future use in the Republic of Serbia.

Chronic, episodic nicotine exposure alters GABAergic synaptic transmission to hypoglossal motor neurons and genioglossus muscle function at a critical developmental age.

Regulation of GABAergic signaling through nicotinic acetylcholine receptor (nAChR) activation is critical for neuronal development. Here, we test the hypothesis that chronic episodic developmental nicotine exposure (eDNE) disrupts GABAergic signaling, leading to dysfunction of hypoglossal motor neurons (XIIMNs), which innervate the tongue muscles. We studied control and eDNE pups at two developmentally vulnerable age ranges: postnatal days (P)1-5 and P10-12. The amplitude and frequency of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs, mIPSCs) at baseline were not altered by eDNE at either age. In contrast, eDNE increased GABAAR-α1 receptor expression on XIIMNs and, in the older group, the postsynaptic response to muscimol (GABAA receptor agonist). Activation of nAChRs with exogenous nicotine increased the frequency of GABAergic sIPSCs in control and eDNE neurons at P1-5. By P10-12, acute nicotine increased sIPSC frequency in eDNE but not control neurons. In vivo experiments showed that the breathing-related activation of tongue muscles, which are innervated by XIIMNs, is reduced at P10-12. This effect was partially mitigated by subcutaneous muscimol, but only in the eDNE pups. Taken together, these data indicate that eDNE alters GABAergic transmission to XIIMNs at a critical developmental age, and this is expressed as reduced breathing-related drive to XIIMNs in vivo.NEW & NOTEWORTHY Here, we provide a thorough assessment of the effects of nicotine exposure on GABAergic synaptic transmission, from the cellular to the systems level. This work makes significant advances in our understanding of the impact of nicotine exposure during development on GABAergic neurotransmission within the respiratory network and the potential role this plays in the excitatory/inhibitory imbalance that is thought to be an important mechanism underlying neonatal breathing disorders, including sudden infant death syndrome.

A Cross-Sectional, Correlational Study Comparing Individual Characteristics of Younger and Older Nursing Home Residents using Western Canadian Resident Assessment Instrument-Minimum Data Set (RAI-MDS) 2.0.

To compare characteristics of nursing home (NH) residents by age categories in Western Canada. A cross-sectional, correlational analysis of secondary data. 89,231 residents living in Western Canada NHs in the provinces of Alberta, Manitoba, and British Columbia in 2016 and2017. Resident characteristics (age, sex, marital status, body mass index, medical diagnoses, cognitive function, physical function, depressive symptoms) came from the Resident Assessment Instrument-Minimum Data Set 2.0 and were analyzed using chi-square, analysis of variance, and post hoc pairwise tests. Human developmental stage age categories were used to create 5 age groups: 18-34, 35-50, 51-64, 65-80, and 81years and older. The demographics, medical diagnoses, cognitive function, and physical function characteristics of NH residents among 5 age groups differed considerably (all P &lt; .001). Residents aged 18-34years were predominately male, never married, with a higher incidence of paralysis and traumatic brain injury. Residents aged 35-50years had a higher incidence of stroke and multiple sclerosis, and residents aged 51-64years mainly were morbidly obese and more prone to depression. Residents aged 65-80years were predominately married and more prone to diabetes, and residents aged 81years and older were predominately widowed, with a higher incidence of dementia compared with others. Findings describe the uniqueness of younger NH age groups and indicate that the youngest NH residents often have the severe disability and a modest support system (as defined by partnered status) compared to older residents in NHs. Future studies must analyze longitudinal data that track the growth of, and changes in, residents' health and functional status.

Correlation of Language Assessment Batteries of Toddlers With Developmental Language Delay

To analyze the correlation between standardized language assessment batteries of toddlers and developmental language delays. A total of 319 children with suspected language developmental delays were enrolled in this study retrospectively. They underwent the Receptive and Expressive Vocabulary Test (REVT) for vocabulary development assessment and at least one of two language assessment batteries: The Sequenced Language Scale for Infants (SELSI) or the Preschool Receptive-Expressive Language Scale (PRES) for language development assessment. The correlation of the results for receptive and expressive language between the scales were analyzed. The participants were divided into two groups: SELSI and REVT (n=45) and PRES and REVT (n=273). When the children's results were classified into groups (average, mild delay, and delay), receptive and expressive scores were significantly correlated with each other in both SELSI-REVT and PRES-REVT groups. In addition, the correlation of mean developmental age between tests are analyzed. In the SELSI-REVT group, there was weak correlation of mean developmental age between tests for receptive and expressive language. In the PRES-REVT group, there was a strong positive correlation of mean developmental age for receptive and expressive language in children aged >36 months. Attention deficits during the test was found to be the statistically significant factor affecting the differences between the tests. The odds ratios for receptive and expressive language were 2.60 (95% confidence interval,1.15-5.84) and 1.94 (95% confidence interval, 1.15-3.27), respectively. This study examined the correlations and influencing factors between language development evaluation tools for toddlers. An integrated interpretation of comprehensive language and vocabulary evaluation tools may be possible in children older than 3 years of language developmental age.

TFIIH mutations can impact on translational fidelity of the ribosome.

TFIIH is a complex essential for transcription of protein-coding genes by RNA polymerase II, DNA repair of UV-lesions and transcription of rRNA by RNA polymerase I. Mutations in TFIIH cause the cancer prone DNA-repair disorder xeroderma pigmentosum (XP) and the developmental and premature aging disorders trichothiodystrophy (TTD) and Cockayne syndrome. A total of 50% of the TTD cases are caused by TFIIH mutations. Using TFIIH mutant patient cells from TTD and XP subjects we can show that the stress-sensitivity of the proteome is reduced in TTD, but not in XP. Using three different methods to investigate the accuracy of protein synthesis by the ribosome, we demonstrate that translational fidelity of the ribosomes of TTD, but not XP cells, is decreased. The process of ribosomal synthesis and maturation is affected in TTD cells and can lead to instable ribosomes. Isolated ribosomes from TTD patients show an elevated error rate when challenged with oxidized mRNA, explaining the oxidative hypersensitivity of TTD cells. Treatment of TTD cells with N-acetyl cysteine normalized the increased translational error-rate and restored translational fidelity. Here we describe a pathomechanism that might be relevant for our understanding of impaired development and aging-associated neurodegeneration.

Is there an optimal window of time for transferring single frozen-thawed euploid blastocysts? A cohort study of 1170 embryo transfers.

Is there an optimal window of time when the transfer of single frozen-thawed euploid blastocysts is associated with a maximal live birth rate (LBR)? Performing a single frozen-thawed euploid blastocyst transfer at 160 ± 4 h post-hCG trigger in modified-natural frozen-thawed embryo transfer (FET) cycles was independently associated with a higher LBR as compared to transfers outside this window; however, in natural FET cycles, LBRs were comparable across a wider range of time intervals. There is compelling evidence for maintaining embryo-endometrial synchrony to optimize clinical outcomes following FETs, which could potentially be achieved by matching the transfer time of an embryo post-ovulation to its developmental age post-oocyte retrieval. For modified-natural cycles, ovulation is widely accepted to occur ∼40 h following the hCG trigger, whilst ovulation following spontaneous LH surge onset is thought to vary from 24 to 56 h. This is a multicentered retrospective cohort study analyzing 1170 single frozen-thawed euploid blastocyst transfers following trophectoderm biopsy and preimplantation genetic testing (PGT) between May 2015 and February 2019. Limiting the analysis to single euploid embryo transfers allowed for a more accurate estimation of the endometrial synchrony factor by controlling for the developmental stage of the embryo (full blastocyst or more advanced) and its genetic composition. LBR per FET was the primary outcome measure. Patients underwent natural or gonadotrophin-induced preparation of the endometrium, with serial serum oestradiol, LH and progesterone measurements. Optimally timed transfers were predefined as those conducted 120 ± 4 h post-ovulation since biopsy and subsequent cryopreservation of full blastocysts which is usually performed at 116-124 h post-oocyte retrieval. This was considered the equivalent of 160 ± 4 h post-hCG trigger in modified-natural cycles (n = 253), as ovulation was assumed to occur ∼40 h after the hCG trigger. For natural cycles (n = 917), this was also considered to be, on average, 160 ± 4 h post the spontaneous LH surge. Thus, study groups were determined as those with optimal timing or not, and additional exploratory and subgroup analyses were performed, varying the time window in terms of onset and width, both overall and per endometrial preparation protocol. Statistical analysis was performed using the generalized estimating equations (GEE) framework to control for the clustered nature of the data while adjusting for potential confounders. Overall, LBRs were significantly higher when the transfer had been performed at 160 ± 4 h post-hCG trigger or LH surge onset compared to when it had been performed outside this window (44.7% vs 36.0%; P = 0.008). A multivariable regression GEE model including the cycle type (natural versus modified-natural), previtrification embryo quality (top versus good quality), embryo stage (fully hatched versus hatching or earlier blastocyst), vitrification day (D5 versus D6) and survival rate (>90% versus <90%) as covariates, confirmed that, overall, embryo transfers conducted 160 ± 4 h post-hCG trigger or LH surge onset (the assumed equivalent of 120 ± 4 h post-ovulation) were associated with a significantly higher LBR (relative risk (RR) 1.21, 95% CI 1.04-1.41). Subgroup exploratory analyses per endometrial preparation protocol demonstrated that these findings were primarily present in the modified-natural cycle group (RR 1.52, 95% CI 1.15-1.99), whilst the natural cycle group showed comparable LBRs across a wider range of time intervals. Moreover, the overall LBR for the natural group (36.8%; 95% CI 33.7-39.9%) was lower than that of the modified-natural group (41.3%; 95% CI 35.4-47.1%), suggesting that there likely remains a greater potential to further optimize the timing of natural cycle embryo transfers. As with all retrospective studies, the presence of residual unknown bias cannot be excluded. Additionally, patients included in this study were a selected group who underwent PGT for specific reasons and hence the results obtained might not be directly applicable to the general population or embryos that have not undergone embryo biopsy. Furthermore, the criteria utilized to interpret hormonal data from natural cycles were specifically adopted for the present study and need to be validated in further studies. The results of this study highlight the significance of embryo-endometrial synchrony for the optimization of frozen embryo transfer outcome. However, it also clearly supports that the implantation window is in most cases wide and the achievement of live birth is possible with relatively high success rates even outside the optimal window of 160 ± 4 h post-trigger for modified-natural cycles and across a range of time intervals for natural cycles. Additionally, this study suggests that implantation rates could be further optimized in natural cycles by improving methods of assessing embryo-endometrial synchrony. C. V. is supported by a National Health and Medical Research Council Early Career Fellowship (GNT1147154). No other funding was received for this study and there are no competing interests. N/A.

Transitioning of protein substitutes in patients with phenylketonuria: evaluation of current practice

BackgroundIn children with phenylketonuria (PKU), transitioning protein substitutes at the appropriate developmental age is essential to help with their long-term acceptance and ease of administration. We assessed the parental experiences in transitioning from a second stage to third stage liquid or powdered protein substitute in patients with PKU.ResultsSixteen interviews (23 open-ended questions) were carried out with parents/caregivers of children with PKU (8 females, 50%) with a median age of 8 years (range 5–11 years), continuously treated with diet, and on a third stage protein substitute. Parents/caregivers identified common facilitators and barriers during the third stage protein substitute transition process. The main facilitators were: child and parent motivation, parent knowledge of the transition process, a role model with PKU, low volume and easy preparation of the third stage protein substitute (liquid/powder), anticipation of increasing child independence, lower parent workload, attractive packaging, better taste and smell, school and teacher support, dietetic plans and guidance, PKU social events, child educational materials and written resources. The main barriers were child aversion to new protein substitutes, poor child behaviour, child aged > 5 years, parental fear of change, the necessity for parental time and persistence, loss of parental control, high product volume, different taste, smell, and texture of new protein substitutes, and peer bullying.ConclusionA stepwise, supportive approach is necessary when transitioning from second to third stage protein substitutes in PKU. Future studies are needed to develop guidance to assist parents/caregivers, health professionals, and teachers during the transition process.

The neuropsychological correlates of (sluggish) cognitive tempo scales in school-aged children

ABSTRACT Sluggish Cognitive Tempo (SCT) is a neuropsychiatric construct including lethargy, behavioral sluggishness, and confusion. A growing number of studies in the literature suggest that this set of symptoms refers to neuropsychological constructs such as sustained attention. However, studies focusing on SCT and its neuropsychological correlates in developmental age are scarce. The present study aims to fill this gap. The Child and Adolescent Behavior Inventory (CABI – Teacher and Parent versions, also including the school functioning scale, and the Child Concentration Inventory (CCI-2) were administered to a sample of 128 Italian primary-school children (57.6% F, mean age 8.81, SD 1.07); the neuropsychological constructs involved in the study were sustained attention and reaction times to two computerized tasks. Bivariate non-parametric correlation analyses yielded significant negative associations between teacher-referred SCT and measures of sustained attention (e.g., the Attentional Network Test and the Hearts and Flowers task) as well as CABI-T school-functioning scale; a small-to-moderate positive correlation was found between CABI-T SCT scores and mean reaction times, as a measure of the slowness of behavioral responses on the Attentional Network Test: this result would appear to represent a fine operationalization of the SCT-characteristic of behavioral sluggishness. Implications of these results for operationalizing the SCT construct in developmental age are discussed.