Developmental differences in children and adults' enforcement of explore versus exploit search strategies in the United States and Turkey.

Across development, as children acquire a deeper understanding of their environment, they explore less and take advantage, or "exploit," what they already know. Here, we test whether children also enforce exploration-oriented search behaviors onto others. Specifically, we ask whether children are more likely to encourage a search agent to explore versus exploit their environment, and whether this pattern varies across childhood (between 3 and 6 years). We also ask whether this pattern differs between children and adults, and generalizes across two different sociocultural contexts-Turkey and the United States-that differ on dimensions that might relate to children's decisions about exploration (e.g., curiosity-focused educational practices, attitudes toward uncertainty avoidance). Participants (N = 358) watched an agent search for rewards and were asked at various points whether the agent should "stay" (exploit) in their current location, or "go" (explore) to a new location. At all points in the experiment, children enforced exploration significantly more often than adults. Early in the agent's search, children in the US enforced exploration more often than children in Turkey; later in the search, younger children (from both sociocultural contexts) were more likely to continue enforcing exploration compared to older children. These findings highlight that children are not only highly exploratory themselves, but also enforce exploration onto others-underscoring the central role that exploration plays in driving early cognitive development across diverse sociocultural contexts. RESEARCH HIGHLIGHTS: The current study examined developmental and cross-cultural differences in children and adults' enforcement of explore-exploit search strategies. Children in the US and Turkey enforced exploration more than adults, who enforced exploitation more often; results were generally consistent across cultures with small differences. Mirroring developmental changes in children's own search behavior; the tendency to enforce exploration decreased between 3- to 6-years of age. Findings underscore the central role of an "exploration mindset" in children's early decision-making-even when exploration has no direct benefits to the child themselves.

The breadth and specificity of 18-month-old's infant-initiated interactions in naturalistic home settings.

Infants actively initiate social interactions aiming to elicit different types of responses from other people. This study aimed to document a variety of communicative interactions initiated by 18-month-old Turkish infants from diverse SES (N = 43) with their caregivers in their natural home settings. The infant-initiated interactions such as use of deictic gestures (e.g., pointing, holdouts), action demonstrations, vocalizations, and non-specific play actions were coded from video recordings and classified into two categories as need-based and non-need-based. Need-based interactions were further classified as a) biological (e.g., feeding); b) socio-emotional (e.g., cuddling), and non-need-based interactions (i.e., communicative intentions) were coded as a) expressive, b) requestive; c) information/help-seeking; d) information-giving. Infant-initiated non-need-based (88%) interactions were more prevalent compared to need-based interactions (12%). Among the non-need-based interactions, 50% aimed at expressing or sharing attention or emotion, 26% aimed at requesting an object or an action, and 12% aimed at seeking information or help. Infant-initiated information-giving events were rare. We further investigated the effects of familial SES and infant sex, finding no effect of either on the number of infant-initiated interactions. These findings suggest that at 18 months, infants actively communicate with their social partners to fulfil their need-based and non-need-based motivations using a wide range of verbal and nonverbal behaviors, regardless of their sex and socio-economic background. This study thoroughly characterizes a wide and detailed range of infant-initiated spontaneous communicative bids in hard-to-access contexts (infants' daily lives at home) and with a traditionally underrepresented non-WEIRD population.

Huntingtin Decreases Susceptibility to a Spontaneous Seizure Disorder in FVN/B Mice.

Huntington disease (HD) is an adult-onset neurodegenerative disorder that is caused by a trinucleotide CAG repeat expansion in the HTT gene that codes for the protein huntingtin (HTT in humans or Htt in mice). HTT is a multi-functional, ubiquitously expressed protein that is essential for embryonic survival, normal neurodevelopment, and adult brain function. The ability of wild-type HTT to protect neurons against various forms of death raises the possibility that loss of normal HTT function may worsen disease progression in HD. Huntingtin-lowering therapeutics are being evaluated in clinical trials for HD, but concerns have been raised that decreasing wild-type HTT levels may have adverse effects. Here we show that Htt levels modulate the occurrence of an idiopathic seizure disorder that spontaneously occurs in approximately 28% of FVB/N mice, which we have called FVB/N Seizure Disorder with SUDEP (FSDS). These abnormal FVB/N mice demonstrate the cardinal features of mouse models of epilepsy including spontaneous seizures, astrocytosis, neuronal hypertrophy, upregulation of brain-derived neurotrophic factor (BDNF), and sudden seizure-related death. Interestingly, mice heterozygous for the targeted inactivation of Htt (Htt+/- mice) exhibit an increased frequency of this disorder (71% FSDS phenotype), while over-expression of either full length wild-type HTT in YAC18 mice or full length mutant HTT in YAC128 mice completely prevents it (0% FSDS phenotype). Examination of the mechanism underlying huntingtin's ability to modulate the frequency of this seizure disorder indicated that over-expression of full length HTT can promote neuronal survival following seizures. Overall, our results demonstrate a protective role for huntingtin in this form of epilepsy and provide a plausible explanation for the observation of seizures in the juvenile form of HD, Lopes-Maciel-Rodan syndrome, and Wolf-Hirschhorn syndrome. Adverse effects caused by decreasing huntingtin levels have ramifications for huntingtin-lowering therapies that are being developed to treat HD.

Exploring individual differences in infants' looking preferences for impossible events: The Early Multidimensional Curiosity Scale.

Infants are drawn to events that violate their expectations about the world: they look longer at physically impossible events, such as when a car passes through a wall. Here, we examined whether individual differences in infants' visual preferences for physically impossible events reflect an early form of curiosity, and asked whether caregivers' behaviors, parenting styles, and everyday routines relate to these differences. In Study 1, we presented infants (N = 47, Mage = 16.83 months, range = 10.29-24.59 months) with events that violated physical principles and closely matched possible events. We measured infants' everyday curiosity and related experiences (i.e., caregiver curiosity-promoting activities) through a newly developed curiosity scale, The Early Multidimensional Curiosity Scale (EMCS). Infants' looking preferences for physically impossible events were positively associated with their score on the EMCS, but not their temperament, vocabulary, or caregiver trait curiosity. In Study 2A, we set out to better understand the relation between the EMCS and infants' looking preferences for physically impossible events by assessing the underlying structure of the EMCS with a larger sample of children (N = 211, Mage = 47.63 months, range = 10.29-78.97 months). An exploratory factor analysis revealed that children's curiosity was comprised four factors: Social Curiosity, Broad Exploration, Persistence, and Information-Seeking. Relatedly, caregiver curiosity-promoting activities were composed of five factors: Flexible Problem-Solving, Cognitive Stimulation, Diverse Daily Activities, Child-Directed Play, and Awe-Inducing Activities. In Study 2B (N = 42 infants from Study 1), we examined which aspects of infant curiosity and caregiver behavior predicted infants' looking preferences using the factor structures of the EMCS. Findings revealed that infants' looking preferences were uniquely related to infants' Broad Exploration and caregivers' Awe-Inducing Activities (e.g., nature walks with infants, museum outings). These exploratory findings indicate that infants' visual preferences for physically impossible events may reflect an early form of curiosity, which is related to the curiosity-stimulating environments provided by caregivers. Moreover, this work offers a new comprehensive tool, the Early Multidimensional Curiosity Scale, that can be used to measure both curiosity and factors related to its development, starting in infancy and extending into childhood.

Untargeted metabolomics and infrared ion spectroscopy identify biomarkers for pyridoxine-dependent epilepsy.

BackgroundPyridoxine-dependent epilepsy (PDE-ALDH7A1) is an inborn error of lysine catabolism that presents with refractory epilepsy in newborns. Biallelic ALDH7A1 variants lead to deficiency of α-aminoadipic semialdehyde dehydrogenase/antiquitin, resulting in accumulation of piperideine-6-carboxylate (P6C), and secondary deficiency of the important cofactor pyridoxal-5'-phosphate (PLP, active vitamin B6) through its complexation with P6C. Vitamin B6 supplementation resolves epilepsy in patients, but intellectual disability may still develop. Early diagnosis and treatment, preferably based on newborn screening, could optimize long-term clinical outcome. However, no suitable PDE-ALDH7A1 newborn screening biomarkers are currently available.MethodsWe combined the innovative analytical methods untargeted metabolomics and infrared ion spectroscopy to discover and identify biomarkers in plasma that would allow for PDE-ALDH7A1 diagnosis in newborn screening.ResultsWe identified 2S,6S-/2S,6R-oxopropylpiperidine-2-carboxylic acid (2-OPP) as a PDE-ALDH7A1 biomarker, and confirmed 6-oxopiperidine-2-carboxylic acid (6-oxoPIP) as a biomarker. The suitability of 2-OPP as a potential PDE-ALDH7A1 newborn screening biomarker in dried bloodspots was shown. Additionally, we found that 2-OPP accumulates in brain tissue of patients and Aldh7a1-knockout mice, and induced epilepsy-like behavior in a zebrafish model system.ConclusionThis study has opened the way to newborn screening for PDE-ALDH7A1. We speculate that 2-OPP may contribute to ongoing neurotoxicity, also in treated PDE-ALDH7A1 patients. As 2-OPP formation appears to increase upon ketosis, we emphasize the importance of avoiding catabolism in PDE-ALDH7A1 patients.FundingSociety for Inborn Errors of Metabolism for Netherlands and Belgium (ESN), United for Metabolic Diseases (UMD), Stofwisselkracht, Radboud University, Canadian Institutes of Health Research, Dutch Research Council (NWO), and the European Research Council (ERC).

Culturally shared and unique meanings and expressions of maternal control across four cultures.

Maternal control is a major dimension of parenting and has different meanings, practices, and potential consequences across cultures. The present study aimed to identify and compare mothers' conceptualizations of parenting control across four cultures to reveal a more nuanced understanding regarding the meaning and practices of control: European American, Chinese immigrant, Korean immigrant, and Turkish. Using a semistructured open-ended interview, 100 European American, 102 U.S. Chinese immigrant, 103 U.S. Korean immigrant, and 109 Turkish mothers of preschool-aged children reported the ratings of importance, specific reasons, and strategies for exerting control over their children in daily life. Results revealed both shared and unique conceptualizations of maternal control across four cultures. Specifically, all mothers reported that it is important to express maternal control over their children in order to set behavioral norms/standards, maintain child safety, support social relations and respect for others, provide guidance, and guide moral development. Moreover, mothers discussed utilizing nonphysical punishment, setting and maintaining rules, reasoning/negotiating, consistency, physical punishment and verbal control, showing parents' serious/stern attitude, correction, and psychological control forms of control. However, the levels at which mothers emphasize the different reasons and strategies varied across cultures, reflecting culturally emphasized values. The findings of the present study further enrich our understanding of the complexities of maternal control across cultures. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

To repeat or not to repeat: Radiologists demonstrated more decisiveness than their fellow radiographers in reducing the repeat rate during mobile chest radiography.

INTRODUCTION: Radiologists and radiographers play a complementary role in providing an optimal image quality with decrease radiation dose and proper diagnosis during chest radiographs. We aim Investigate years of experience among radiologists and radiographers on perception of image quality and its impact on repeat rate when evaluating portable pediatric chest radiographs. METHODS: IRB approved retrospective study consisted of randomly selected images (n = 131) of pediatric portable chest radiographs. Images were blindly assessed by four radiologists and four radiographers. Readers were asked to assess qualitative and quantitative image quality by rating: image quality, decision to repeat and image technique. All data was compared employing Pearson's Correlation, Visual grading characteristic (VGC) and Cohens' kappa analyses. RESULTS: Image quality: Radiologists (88.4%) rated images as excellent significantly more than radiographers (11.6%), and radiographers (90.1%) as poor significantly more than radiologists (9.9%) (p < 0.05). Repeat: Radiologists (57%) decided not to repeat images significantly more than radiographers (43%) (p < 0.05). Image technique: Radiologists rated images as acceptable (65%) and excellent (97.7%) significantly more than radiographers (35% and 2.3% respectively) (p < 0.05), whereas radiographers (84%) assessed image technique as poor significantly more than radiologists (16%) (p < 0.05). VGC: radiographers had slightly better qualitative evaluation of image quality than radiologists. An association between image quality (p < 0.002) and repeat decision (p < 0.044) with years of experience was established when comparing years of experience with image assessment rubric, while no association was noted with image technique (p < 0.9). CONCLUSION: Radiologists demonstrated more decisiveness than their fellow radiographers in reducing the repeat rate of portable pediatric chest radiographs. Interestingly, years of experience only seem to affect image technique and image quality assessment among radiologists. IMPLICATIONS FOR PRACTICE: Continuous education of radiographers and close collaboration with radiologists is crucial to achieve optimal image quality and low radiation doses.

A novel mouse model for pyridoxine-dependent epilepsy due to antiquitin deficiency.

Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disease caused by mutations in the ALDH7A1 gene leading to blockade of the lysine catabolism pathway. PDE is characterized by recurrent seizures that are resistant to conventional anticonvulsant treatment but are well-controlled by pyridoxine (PN). Most PDE patients also suffer from neurodevelopmental deficits despite adequate seizure control with PN. To investigate potential pathophysiological mechanisms associated with ALDH7A1 deficiency, we generated a transgenic mouse strain with constitutive genetic ablation of Aldh7a1. We undertook extensive biochemical characterization of Aldh7a1-KO mice consuming a low lysine/high PN diet. Results showed that KO mice accumulated high concentrations of upstream lysine metabolites including ∆1-piperideine-6-carboxylic acid (P6C), α-aminoadipic semialdehyde (α-AASA) and pipecolic acid both in brain and liver tissues, similar to the biochemical picture in ALDH7A1-deficient patients. We also observed preliminary evidence of a widely deranged amino acid profile and increased levels of methionine sulfoxide, an oxidative stress biomarker, in the brains of KO mice, suggesting that increased oxidative stress may be a novel pathobiochemical mechanism in ALDH7A1 deficiency. KO mice lacked epileptic seizures when fed a low lysine/high PN diet. Switching mice to a high lysine/low PN diet led to vigorous seizures and a quick death in KO mice. Treatment with PN controlled seizures and improved survival of high-lysine/low PN fed KO mice. This study expands the spectrum of biochemical abnormalities that may be associated with ALDH7A1 deficiency and provides a proof-of-concept for the utility of the model to study PDE pathophysiology and to test new therapeutics.

PLPHP deficiency: clinical, genetic, biochemical, and mechanistic insights.

Biallelic pathogenic variants in PLPBP (formerly called PROSC) have recently been shown to cause a novel form of vitamin B6-dependent epilepsy, the pathophysiological basis of which is poorly understood. When left untreated, the disease can progress to status epilepticus and death in infancy. Here we present 12 previously undescribed patients and six novel pathogenic variants in PLPBP. Suspected clinical diagnoses prior to identification of PLPBP variants included mitochondrial encephalopathy (two patients), folinic acid-responsive epilepsy (one patient) and a movement disorder compatible with AADC deficiency (one patient). The encoded protein, PLPHP is believed to be crucial for B6 homeostasis. We modelled the pathogenicity of the variants and developed a clinical severity scoring system. The most severe phenotypes were associated with variants leading to loss of function of PLPBP or significantly affecting protein stability/PLP-binding. To explore the pathophysiology of this disease further, we developed the first zebrafish model of PLPHP deficiency using CRISPR/Cas9. Our model recapitulates the disease, with plpbp-/- larvae showing behavioural, biochemical, and electrophysiological signs of seizure activity by 10 days post-fertilization and early death by 16 days post-fertilization. Treatment with pyridoxine significantly improved the epileptic phenotype and extended lifespan in plpbp-/- animals. Larvae had disruptions in amino acid metabolism as well as GABA and catecholamine biosynthesis, indicating impairment of PLP-dependent enzymatic activities. Using mass spectrometry, we observed significant B6 vitamer level changes in plpbp-/- zebrafish, patient fibroblasts and PLPHP-deficient HEK293 cells. Additional studies in human cells and yeast provide the first empirical evidence that PLPHP is localized in mitochondria and may play a role in mitochondrial metabolism. These models provide new insights into disease mechanisms and can serve as a platform for drug discovery.

Perceptions of Obesity Prevention Policies: Socioeconomic Assessment in the Turkish Capital.

PURPOSE: The purpose of this study was to inform public policy opportunities to reduce childhood obesity by identifying parents' perceptions of factors contributing to childhood obesity, attribution of responsibility, and the extent of their support for public prevention policies with attention to socio-economic status. DESIGN AND METHODS: In 2015, 2066 parent-child dyads across socio-economic strata from 43 randomly selected schools in Ankara completed surveys and measurements to examine perceptions, attribution, and prevention policies related to childhood obesity. RESULTS: Parents across the socio-demographic spectrum recognized obesity as a serious problem. Unhealthy food availability was identified as the leading cause of while industry and media were credited with having the greatest responsibility for childhood obesity. There was strong public support for policy strategies targeting schools, marketing, and the built environment, though support tempered as socio-economic status and parental education decreased. CONCLUSIONS: This survey provided insight into parents' knowledge and beliefs surrounding childhood obesity as well as their endorsement of related prevention strategies. Educational messages that address variations in SES to describe the causes of childhood obesity and connect those causes to actionable community prevention strategies may improve community support for enhanced policy actions within and beyond school settings.

Neuronal plasticity in a case with total hemispheric lesion.

RATIONALE: The adult brain maintains the ability for reorganization or plasticity throughout life. Non-invasive techniques such as functional magnetic resonance imaging (f-MRI), Transcranial Magnetic Stimulation (TMS) and magnetoencephalography could be used to show recovery of function after stroke. OBJECTIVE: Explanation of neuronal plastisity and intra-hemisferic reorganization with functional recovery of a case who has total extensive damage on the left hemisphere. case report: Twenty-five years old female patient was admitted to our hospital with a right-sided sequel hemiparesis and homonymous hemianopia. She had right-sided paresia after an inguinal hernia operation when she was one and a half years old. On neurological examination she was speaking fluently, and cooperated on complicated comments. Motor examination revealed right-sided spastic hemiparesis predominant on distal parts and right sided visual field defect. But she was continuing her activity of daily livings without help. Her detailed neuropsycological examination revealed mild cognitive dysfunction. Cranial MRI showed total left hemisphere encephalomalasia. Right hemisphere function was noticed on task-related brain activation during voluntary movement of her right leg (she was not capable of performing right hand function tasks by herself ) on functional MRI. CONCLUSION: Cerebral lesions in the early life can be compensated with the unaffected hemisphere by the neuronal reorganisation and a patient with complete left hemisphere lesion such as our patient can speak, maintain her life without assistance but with mild cognitive decline, compared with elderly stroke patients.

Cyanine dyes for the detection of double stranded DNA.

Twenty three novel cyanine dyes have been applied as fluorescent stains for the detection of nucleic acids in agarose gel electrophoresis. Significant fluorescence enhancement of these dyes in the presence of double stranded DNA was observed. Five dyes offered superior sensitivity in the detection and quantification of DNA, over Ethidium Bromide, the most commonly used nucleic acid stain.

Synthesis of a new series of heterocyclic scaffolds for medicinal purposes.

A new series of substituted 8-fluro-4H-pyrimido[2,1-b] [1,3]benzothiazole-4-ones () substituted 7-methyl-4H-isoxazolo[2,3-a]pyrimidin-4-ones, and substituted 2-methyl-5,6,7,8-tetrahydro-9H-isoxazolo[2,3-a]pyridopyrimidin-9-ones, compounds I-VII, have been prepared via condensation of beta-keto esters with 2-aminopyridine derivatives, in the presence of polyphosphoric acid. The same technique has also been used to prepare diazepine compounds, VIII-X, by condensation of a gamma-keto ester with 2-aminopyridine derivatives. Details of synthetic procedures are shown. The new compounds have been characterized by elemental analysis, GC-MS, FT-IR and NMR spectrometry. Antibacterial, antifungal and anticancer (cytotoxic) activities, for three of these compounds, have been investigated and are presented.

Size fractionation and characterization of natural colloids by flow-field flow fractionation coupled to multi-angle laser light scattering.

Flow-field flow fractionation (FlFFF) coupled to multi-angle laser light scattering (MALLS) was evaluated for size and shape determination of standard spherical and arbitrarily shaped natural colloids. Different fitting methods for light scattering data retrieved from MALLS were evaluated to determine the particle size of spherical standards and natural colloids. In addition, FlFFF was optimized for best fractionation in connection to MALLS, minimal colloids-membrane interaction, and minimal sample losses. FlFFF, calibrated with standard particles, was used to determine hydrodynamic diameter, or radius (D(h) or R(h)), of the fractionated colloids, whereas the MALLS was used to determine root mean square radius of gyration (R(g)) for fractionated colloids. Combining both results, by calculating the R(g)/R(h) ratio, allows an estimation of colloid deviation from the shape of homogeneous sphere. Accordingly, this study demonstrates that, FlFFF-MALLS is a valuable technique for characterizing heterogeneous and arbitrarily shaped natural colloidal particles in terms of size and shape. To check the usefulness of FlFFF-MALLS in natural colloid studies, the technique was used to investigate the sedimentation behavior of extracted soil colloidal particles. Results illustrate that, in a silty till sample, carbonates function as cement between the colloidal particles, and consequently, change their sedimentation behavior. On the other hand, carbonate dissolution generates a more homogeneous colloidal sample.