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Despite increasing awareness for diagnosing autism spectrum disorder (ASD) and initiating treatments early in life, many children and adolescents continue to be diagnosed at a relatively older age. Focusing on children who first received an ASD diagnosis at age six or older, this study aimed to describe the symptoms that parents reported when ASD was diagnosed, follow the patients' clinical trajectory prior to receiving the diagnosis, and describe differences in symptoms and prior diagnoses between males and females cases. We included 258 children (205 males and 53 females) who were first diagnosed with autism at age 6-18 in 2017-2018. We retrieved demographic information, neurologic and developmental symptoms, diagnoses, and medications dispensing history from the children's electronic medical charts. The data indicated that prior diagnoses of language delays and attention deficit hyperactivity disorder were common among children with a late ASD diagnosis. Two thirds of the children were prescribed one or more medications to treat psychosocial and behavioral conditions before receiving a late ASD diagnosis. Difficulties in social relationships with peers were the leading reported symptoms by parents at the time of ASD diagnosis. Across these different domains, some differences were found between males and females, including a somewhat higher cognitive level in males, who were also more likely to present aggressive behavior.

The aim of this report is to call attention to a unique clinical group of children who are not diagnosed with ASD but exhibit excessive interest in specific topics or repetitive behaviors. It is argued that this group might require specific developmental stimulation, especially in light of the fact that it does not receive adequate professional treatment or support. The results of conducted surveys are supplemented with additional diagnostic and anamnestic data from which practical conclusions based on research evidence are drawn and general guidelines for intervention are formulated. Further research into this group is also suggested.

Background: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two neurodevelopmental disorders that share common symptoms and frequently co-occur. We performed a systematic review of studies examining three main domains in ADHD vs ASD; executive functions, brain structures and functions, and emotional skills, in an effort to better understand their co-occurrence.Methods: As ADHD and ASD frequently co-occur, we chose to focus on the relevant articles comparing ADHD (with no ASD) and ASD (with no ADHD) populations using appropriate measures. A systematic literature search was conducted using six electronic databases, up to May 18, 2022.Results: A total of 19 articles were included. No significant differences were found in executive functioning between ADHD and ASD. For emotional skills, results were inconclusive, with greater theory of mind (ToM) and empathy skills in ADHD relative to ASD, but no significant differences in emotion recognition. Regarding brain structure and functions, there were inconsistent findings, with some studies reporting weaker brain connectivity in ASD, and reduced gray and white matter volumes in ADHD, while others reported no significant differences.Conclusions: Our review suggests a lack of studies directly examining ASD compared with ADHD. The existing literature does not suggest a unique association of either ASD/ADHD with executive dysfunction, emotional skills deficits, or brain structure/function abnormalities. Consequently, further research is necessary to develop a more comprehensive understanding of the overlaps and differences between these disorders and to address the existing gaps in knowledge.

PDF file - 856K, Supplementary Table 1, presenting Conditional logistic regression model relating the three biomarkers OGG1, MPG and APE1 to lung cancer. Supplementary Figure 1, presenting Association of DNA repair activity with lung cancer risk, including relative frequency plots for APE1 activity in 100 case patients and 99 matched controls subjects, relative frequency plots for the integrated DNA repair OMA score in 100 case patients and 99 matched controls subjects, and odds ratio calculated as a function of the percentiles of the distribution of the OMA score among the control subjects.

Clinical observations suggest that girls suspected to have ASD manage to perform better in social and emotional tasks than boys, leading to a camouflage effect which results in the under-diagnosis ...

We examined group differences between parents, both mothers and fathers, of premature and full-term infants to determine whether they differed in their reports of subjective parenting stress and in their level of parental reflective functioning (PRF). We also tested whether each parent's reflective functioning moderated the links between birth status (prematurity vs. full-term) and parenting stress. A sample of 73 cohabiting, heterosexual Israeli families with a premature (28–36th week gestational age, N = 34) or full-term infant (37th week and above gestational age, N = 39) participated, comprising the two parents' groups. Infants' age averaged 7.07 months (SD = 1.28). Each parent completed the Parent Stress Inventory (PSI) individually to determine his/her subjective personal and childrearing stress levels. The Parent Development Interview (PDI-R2-S) was used to obtain each parent's PRF (self and child/relation-focused) level. Findings showed that the premature and full-term parents did not differ in their PSI scores or PRF levels. However, mothers' self-focused PRF moderated the link between prematurity and personal parenting stress, whereas fathers' self-focused PRF moderated the link between prematurity and childrearing parenting stress. Furthermore, fathers' and mothers' PRF operated differently in the premature and full-term parents' groups. The findings highlight the importance of mothers' and fathers' PRF in predicting parents' subjective stress in general and particularly in the case of infant prematurity. We discuss these findings and their relevance for preventive and therapeutic perinatal interventions.

Purpose: The craniometrics of head circumference (HC) and ventricular size are part of the clinical assessment of infants with hydrocephalus and are often utilized in conjunction with other clinical and radiological parameters to determine the success of treatment. We aimed to assess the effect of endoscopic third ventriculostomy (ETV) and shunting on craniometric measurements during the follow-up of a cohort of infants with symptomatic triventricular hydrocephalus secondary to aqueductal stenosis. Methods: We performed a post hoc analysis of data from the International Infant Hydrocephalus Study (IIHS)-a prospective, multicenter study of infants (< 24 months old) with hydrocephalus from aqueductal stenosis who were treated with either an ETV or shunt. During various stages of a 5-year follow-up period, the following craniometrics were measured: HC, HC centile, HC z-score, and frontal-occipital horn ratio (FOR). Data were compared in an analysis of covariance, adjusting for baseline variables including age at surgery and sex. Results: Of 158 enrolled patients, 115 underwent an ETV, while 43 received a shunt. Both procedures led to improvements in the mean HC centile position and z-score, a trend which continued until the 5-year assessment point. A similar trend was noted for FOR which was measured at 12 months and 3 years following initial treatment. Although the values were consistently higher for ETV compared with shunt, the differences in HC value, centile, and z-score were not significant. ETV was associated with a significantly higher FOR compared with shunting at 12 months (0.52 vs 0.44; p = 0.002) and 3 years (0.46 vs 0.38; p = 0.03) of follow-up. Conclusion: ETV and shunting led to improvements in HC centile, z-score, and FOR measurements during long-term follow-up of infants with hydrocephalus secondary to aqueductal stenosis. Head size did not significantly differ between the treatment groups during follow-up, however ventricle size was greater in those undergoing ETV when measured at 1 and 3 years following treatment.

The lockdown that was imposed by governments as part of the attempt to contain the COVID-19 pandemic included extreme measures, such as home confinement and the shutting down of special education systems. Our aim was to learn about the core experiences of parents of children with autism during this significant life disturbance. Thirty-one parents of 25 children with autism participated in semi-structured telephone interviews which were transcribed verbatim and underwent a qualitative, immersion/crystallization analysis. The analysis was conducted in an iterative consensus-building process to identify parents’ experiences, concerns, challenges, coping strategies, and perceived needs during the lockdown. The main themes that emerged related to the various parental concerns; the major difficulties encountered during this unique time, the functional, social, and behavioral implications the lockdown had on these children; and the manner in which the parents coped as an indication of their resourcefulness and outlook. Our findings broaden the insight into the underlying elements of the hardships and gains experienced by children with autism and their parents in times of significant life adversity. Programs in such times should be directed at supporting and guiding parents on how to better accommodate to the situation, thereby optimizing their coping strategies and resilience. Lay abstract The lockdown and home isolation due to the COVID-19 pandemic led to significant transformation in lifestyles. Being a parent in this situation was not easy for anyone, much less for parents of children with special needs. The shutting down of special education systems meant that parents lost a vital support network and had to be the sole full-time caregivers despite often lacking the skills to cope with this new and daunting situation. We interviewed parents and learned that the main difficulties faced by homebound autistic children stemmed from the change in routine, lack of special education services, limited physical space, and food- and sleep-related issues. Some children experienced worsening in behavioral, social, and developmental domains, yet others seemed to not only overcome the challenges of changing conditions but even benefit from them. The children’s success or failure was directly related to how their parents coped. The key factors that enabled successful coping were the parents’ ability to accommodate to the child’s needs, their own creativeness and resourcefulness, and a generally positive outlook. The results of this analysis revealed that the best way to benefit autistic children caught up in drastic changes in their routine lifestyle is to invest in a strong support system for their parents.

Background Improving lung cancer risk assessment is required because current early-detection screening criteria miss most cases. We therefore examined the utility for lung cancer risk assessment of a DNA Repair score obtained from OGG1, MPG, and APE1 blood tests. In addition, we examined the relationship between the level of DNA repair and global gene expression. Methods We conducted a blinded case-control study with 150 non–small cell lung cancer case patients and 143 control individuals. DNA Repair activity was measured in peripheral blood mononuclear cells, and the transcriptome of nasal and bronchial cells was determined by RNA sequencing. A combined DNA Repair score was formed using logistic regression, and its correlation with disease was assessed using cross-validation; correlation of expression to DNA Repair was analyzed using Gene Ontology enrichment. Results DNA Repair score was lower in case patients than in control individuals, regardless of the case’s disease stage. Individuals at the lowest tertile of DNA Repair score had an increased risk of lung cancer compared to individuals at the highest tertile, with an odds ratio (OR) of 7.2 (95% confidence interval [CI] = 3.0 to 17.5; P Conclusions The DNA Repair score, previously shown to be a lung cancer risk factor in the Israeli population, was validated in this independent study as a mechanism-based cancer risk biomarker and can substantially improve current lung cancer risk prediction, assisting prevention and early detection by computed tomography scanning.

Knowledge regarding the association between functional connectivity and white-matter (WM) maturation of motor and visual networks in preterm infants at term equivalent age (TEA) and their association with behavioral outcome is currently limited. Thirty-two preterm infants born

One of the most important unanswered questions in pediatric hydrocephalus is determining whether treatment with endoscopic third ventriculostomy (ETV) versus shunt results in improved health status and quality of life (QOL). To answer this, the International Infant Hydrocephalus Study (IIHS) was started in 2005 as a prospective, multicenter study to compare ETV and shunt in infants (

Purpose: To examine the feasibility and efficacy of a combined motor-cognitive training using virtual reality to enhance behavior, cognitive function and dual-tasking in children with Atten...

This case series assesses white matter microstructure of the cerebellar peduncles in 4 adolescents born preterm with enlarged ventricles and reduced white matter volume in the cerebrum but no apparent injury to the cerebellum. Subjects (ages 12-17 years, gestational age 26-32 weeks, birth weight 825-2211 g) were compared to a normative sample of 19 full-term controls (9-17 years, mean gestational age 39 weeks, mean birth weight 3154 g). Tract profiles for each of the cerebellar peduncles were generated by calculating fractional anisotropy at 30 points along the central portion of each tract. One or more case subjects exhibited higher fractional anisotropy beyond the 90th percentile in the inferior, middle, and superior cerebellar peduncles. Findings demonstrate that differences in cerebellar white matter microstructure can be detected in the absence of macrostructural cerebellar abnormalities.

Summary We developed radioactivity-based and fluorescence-based assays for the DNA repair enzyme APE1 and showed that its decreased activity is associated with increased lung cancer risk. This suggests that ‘bad DNA repair’ rather than ‘bad luck’ is involved in cancer etiology., The key role of DNA repair in removing DNA damage and minimizing mutations makes it an attractive target for cancer risk assessment and prevention. Here we describe the development of a robust assay for apurinic/apyrimidinic (AP) endonuclease 1 (APE1; APEX1), an essential enzyme involved in the repair of oxidative DNA damage. APE1 DNA repair enzymatic activity was measured in peripheral blood mononuclear cell protein extracts using a radioactivity-based assay, and its association with lung cancer was determined using conditional logistic regression with specimens from a population-based case–control study with 96 lung cancer cases and 96 matched control subjects. The mean APE1 enzyme activity in case patients was 691 [95% confidence interval (CI) = 655–727] units/ng protein, significantly lower than in control subjects (mean = 793, 95% CI = 751–834 units/ng protein, P = 0.0006). The adjusted odds ratio for lung cancer associated with 1 SD (211 units) decrease in APE1 activity was 2.0 (95% CI = 1.3–3.1; P = 0.002). Comparison of radioactivity- and fluorescence-based assays showed that the two are equivalent, indicating no interference by the fluorescent tag. The APE1Asp148Glu SNP was associated neither with APE1 enzyme activity nor with lung cancer risk. Taken together, our results indicate that low APE1 activity is associated with lung cancer risk, consistent with the hypothesis that ‘bad DNA repair’, rather than ‘bad luck’, is involved in cancer etiology. Such assays may be useful, along with additional DNA repair biomarkers, for risk assessment of lung cancer and perhaps other cancers, and for selecting individuals to undergo early detection techniques such as low-dose CT.

Intact development of cerebellar connectivity is essential for healthy neuromotor and neurocognitive development. To date, limited knowledge about the microstructural properties of the cerebellar peduncles, the major white matter tracts of the cerebellum, is available for children and adolescents. Such information would be useful as a comparison for studies of normal development, clinical conditions, or associations of cerebellar structures with cognitive and motor functions. The goal of the present study was to evaluate the variability in diffusion measures of the cerebellar peduncles within individuals and within a normative sample of healthy children. Participants were 19 healthy children and adolescents, aged 9-17 years, mean age 13.0 ± 2.3. We analyzed diffusion magnetic resonance imaging (dMRI) data with deterministic tractography. We generated tract profiles for each of the cerebellar peduncles by extracting four diffusion properties (fractional anisotropy (FA) and mean, radial, and axial diffusivity) at 30 equidistant points along each tract. We were able to identify the middle cerebellar peduncle and the bilateral inferior and superior cerebellar peduncles in all participants. The results showed that within each of the peduncles, the diffusion properties varied along the trajectory of the tracts. However, the tracts showed consistent patterns of variation across individuals; the coefficient of variation for FA across individual profiles was low (≤20%) for each tract. We observed no systematic variation of the diffusion properties with age. These cerebellar tract profiles of the cerebellar peduncles can serve as a reference for future studies of children across the age range and for children and adolescents with clinical conditions that affect the cerebellum.

Six medical disciplines are responsible for assessment, diagnosis and treatment of people with attention deficiency hyperactivity disorder (ADHD) in Israel: family doctors, pediatricians, adult and child neurologists, adult and child psychiatrists.To investigate differences in ADHD diagnostic practices between three different pediatric subspecialties in the clinical setting in order to establish a common ground for a future unified approach.An anonymous web-based questionnaire was administered to child psychiatrists, pediatric neurologists and general pediatricians who are actively involved in ADHD diagnosis (n=104).Neurologists and pediatricians rarely use the mental status examination, while psychiatrists rarely perform a neurological or physical examination (P0.0001). A general clinical impression of learning abilities and/or neurodevelopmental skills was implemented more often by pediatric neurologists (P0.04).The significant differences found between the three medical specialties with regard to the clinical evaluation of ADHD could be attributed, at least in part, to the ambiguity of available guidelines concerning the clinical examination, and to the adherence of each specialty to its own "skills." Larger surveys in other countries should be considered and an effort made to create a common, "inter-disciplinary" ground on this important part of ADHD evaluation, differential diagnosis, and research.

Reading is a critical life skill in the modern world. The neural basis of reading incorporates a distributed network of cortical areas and their white matter connections. The cerebellum has also been implicated in reading and reading disabilities. However, little is known about the contribution of cerebellar white matter pathways to major component skills of reading. We used diffusion magnetic resonance imaging (dMRI) with tractography to identify the cerebellar peduncles in a group of 9–17 year old children and adolescents born full term (n=19) or preterm (n=26). In this cohort, no significant differences were found between fractional anisotropy (FA) measures of the peduncles in the preterm and full term groups. FA of the cerebellar peduncles correlated significantly with measures of decoding and reading comprehension in the combined sample of full term and preterm subjects. Correlations were negative in the superior and inferior cerebellar peduncles and positive in the middle cerebellar peduncle. Additional analyses revealed that full term and preterm groups demonstrated similar patterns of reading associations within the left SCP, MCP and left ICP. Partial correlation analyses showed that distinct sub-skills of reading were associated with FA in segments of different cerebellar peduncles. Overall, the present findings are the first to document associations of microstructure of the cerebellar peduncles and the component skills of reading.

DNA repair is a major mechanism for minimizing mutations and reducing cancer risk. Here, we present the development of reproducible and specific enzymatic assays for methylpurine DNA glycosylase (MPG) repairing the oxidative lesions 1,N6-ethenoadenine (εA) and hypoxanthine (Hx) in peripheral blood mononuclear cells protein extracts. Association of these DNA repair activities with lung cancer was determined using conditional logistic regression with specimens from a population-based case-control study with 96 lung cancer cases and 96 matched control subjects. The mean MPG-εA in case patients was 15.8 units/μg protein (95% CI 15.3-16.3), significantly higher than in control subjects-15.1 (14.6-15.5), *P = 0.011. The adjusted odds ratio for lung cancer associated with a one SD increase in MPG-εA activity (2.48 units) was significantly bigger than 1 (OR = 1.6, 95% CI = 1.1-2.4; *P = 0.013). When activity of OGG1, a different DNA repair enzyme for oxidative damage, was included in the model, the estimated odds ratio/SD for a combined MPG-εA-OGG1 score was 2.6 (95% CI 1.6-4.2) *P = 0.0001, higher than the odds ratio for each single assay. The MPG enzyme activity assays described provide robust functional risk biomarkers, with increased MPG-εA activity being associated with increased lung cancer risk, similar to the behavior of MPG-Hx. This underscores the notion that imbalances in DNA repair, including high DNA repair, usually perceived as beneficial, can cause cancer risk. Such DNA repair risk biomarkers may be useful for risk assessment of lung cancer and perhaps other cancer types, and for early detection techniques such as low-dose CT.

Background Food aversion and nutritional difficulties are common in children with autism spectrum disorder. Aim To compare meal time behavior of children with autism to their typically developing siblings and to typical controls and to examine if sensory profiles can predict meal time behavior or nutritional deficiencies in the autism group.

Only a minority of smokers develop lung cancer, possibly due to genetic predisposition, including DNA repair deficiencies. To examine whether inter-individual variations in DNA repair activity of N-methylpurine DNA glycosylase (MPG) are associated with lung cancer, we conducted a blinded, population-based, case–control study with 100 lung cancer case patients and 100 matched control subjects and analyzed the data with conditional logistic regression. All statistical tests were two-sided. MPG enzyme activity in peripheral blood mononuclear cells from case patients was higher than in control subjects, results opposite that of 8-oxoguanine DNA glycosylase (OGG1) DNA repair enzyme activity. For lung cancer associated with one standard deviation increase in MPG activity, the adjusted odds ratio was 1.8 (95% confidence interval [CI] = 1.2 to 2.6; P = .006). A combined MPG and OGG1 activities score was more strongly associated with lung cancer risk than either activity alone, with an odds ratio of 2.3 (95% CI = 1.4 to 3.6; P < .001). These results form a basis for a future panel of risk biomarkers for lung cancer risk assessment and prevention.

Objective: Knowing how adults with ADHD interact with prerecorded video lessons at home may provide a novel means of early screening and long-term monitoring for ADHD. Method: Viewing patterns of 484 students with known ADHD were compared with 484 age, gender, and academically matched controls chosen from 8,699 non-ADHD students. Transcripts generated by their video playback software were analyzed using t tests and regression analysis. Results: ADHD students displayed significant tendencies ( p ≤ .05) to watch videos with more pauses and more reviews of previously watched parts. Other parameters showed similar tendencies. Regression analysis indicated that attentional deficits remained constant for age and gender but varied for learning experience. Conclusion: There were measurable and significant differences between the video-viewing habits of the ADHD and non-ADHD students. This provides a new perspective on how adults cope with attention deficits and suggests a novel means of early screening for ADHD.

Epileptic negative myoclonus is an uncommon seizure type characterized by a sudden, brief loss of muscle tone that may lead to falling. It has been associated largely with benign childhood epilepsy with centrotemporal spikes (rolandic epilepsy), although it may also be a feature of other epileptic syndromes. In patients with rolandic epilepsy, epileptic negative myoclonus usually appears during the course of the disease, well after a diagnosis of the epilepsy has been established. Described here are five patients with rolandic epilepsy in which the presenting seizure was falls due to epileptic negative myoclonus. Because developmental delay or neurocognitive problems were present in three of the children, it is possible that epileptic negative myoclonus may be misinterpreted as clumsiness-related falls in some children who actually have undiagnosed rolandic epilepsy.

This long-term, prospective study evaluated repeatedly school readiness and adjustment at kindergarten and first grade of children with extreme intrauterine growth restriction (IUGR; n = 20) in relation to controls (n = 19). Methods included individual testing of cognitive competence, self-perception, motivation, loneliness and academic achievements; parental anxiety and family-functioning; and teacher ratings of cognitive, emotional, and social adjustment. Children with IUGR had lower cognitive and achievement scores and frequent impulsivity. However, they experienced no socioemotional difficulties. Children in this group, particularly boys, who had mild cognitive difficulties, rule breaking tendencies, and social adjustment issues experienced academic adjustment difficulties during the first school year. Findings underscore a susceptibility of children born with extreme IUGR to develop learning difficulties, and highlight their initial socioemotional resilience.

While the role of reduced DNA repair in susceptibility to hereditary cancers is well established, its role in sporadic cancer is less understood. One of the reasons is the lack of specific DNA repair assays that are suitable for epidemiology studies. Here we describe the development of the OGG test, an epidemiology-grade enzymatic assay for the activity of the base excision repair enzyme 8-oxoguanine DNA glycosylase, in protein extracts prepared from human blood cells. The assay is robust and reproducible, with a coefficient of variation of 10%. Using the OGG test we determined OGG activity in 120 healthy individuals. Our results show an inter-individual variation of 2.8-fold in OGG activity, from 3.6 up to 10.1 units/μg protein, with a mean value of 7.2 units/μg protein. There was no significant difference in OGG activity between males and females, or between smokers and non-smokers. Interestingly, there was a gender-specific effect of age: OGG activity was slightly but significantly lower in males older than the age of 55 years compared to younger males, but not in females at the same age groups. Analysis of OGG1 mRNA by quantitative real-time RT-PCR showed a group trend of an increase in OGG enzymatic activity with increasing mRNA expression, but the correlation between activity and mRNA in individuals was poor, indicating the importance of factors other than mRNA expression. The OGG test described is expected to be useful in studying the role of 8-oxoguanine repair in cancer, as recently demonstrated for non-small cell lung cancer [T. Paz-Elizur, M. Krupsky, S. Blumenstein, D. Elinger, E. Schechtman, Z. Livneh, J. Natl. Cancer Inst. 95 (2003) 1312–1319]. In addition, it may serve as a paradigm for the development of additional functional DNA repair tests, which are needed in order to gain further insight into the role of DNA repair in cancer risk and pathology.

Translesion DNA synthesis (TLS) is a DNA damage tolerance mechanism carried out by low-fidelity DNA polymerases that bypass DNA lesions, which overcomes replication stalling. Despite the miscoding nature of most common DNA lesions, several of them are bypassed in mammalian cells in a relatively accurate manner, which plays a key role maintaining a low mutation load. Whereas it is generally agreed that TLS across the major UV and sunlight induced DNA lesion, the cyclobutane pyrimidine dimer (CPD), is accurate, there were conflicting reports on whether the same is true for the thymine–thymine pyrimidine–pyrimidone(6-4) ultraviolet light photoproduct (TT6-4PP), which represents the second most common class of UV lesions. Using a TLS assay system based on gapped plasmids carrying site-specific TT6-4PP lesions in defined sequence contexts we show that the DNA sequence context markedly affected both the extent and accuracy of TLS. The sequence exhibiting higher TLS exhibited also higher error-frequency, caused primarily by semi-targeted mutations, at the nearest nucleotides flanking the lesion. Our results resolve the discrepancy reported on TLS across TT6-4PP, and suggest that TLS is more accurate in human cells than in mouse cells.

Studies on the carotenoid-overaccumulating structures in chromoplasts have led to the characterization of proteins termed plastid lipid-associated proteins (PAPs), involved in the sequestration of hydrophobic compounds. Here we characterize the PAP CHRD, which, based on sequence homology, belongs to a highly conserved group of proteins, YER057c/YjgF/UK114, involved in the regulation of basic and vital cellular processes in bacteria, yeast and animals. Two nuclear genes were characterized in tomato plants: one (LeChrDc) is constitutively expressed in various tissues and the other (LeChrDi) is induced by stress in leaves and is upregulated by developmental cues in floral tissues. Using RNAi and antisense approaches, we show their involvement in biologically significant processes such as photosynthesis. The quantum yield of photosynthetic electron flow in transgenic tomato leaves with suppressed LeChrDi/c expression was 30-50% of their control, non-transgenic counterparts and was ascribed to lower PSI activity. Transgenic flowers with suppressed LeChrDi/c also accumulated up to 30% less carotenoids per unit protein as compared to control plants, indicating an interrelationship between PAPs and floral-specific carotenoid accumulation in chromoplasts. We suggest that CHRD's role in the angiosperm reproductive unit may be a rather recent evolutionary development; its original function may have been to protect the plant under stress conditions by preserving plastid functionality.

This study examines long-term effects of antenatal management of intrauterine growth restriction (IUGR) on developmental outcome and on maternal coping using a prospective cross-sectional design. Sixty-nine families were evaluated using psychological testing and risk questionnaires. The effects of timing of diagnosis (prenatal/perinatal) and of pregnancy management [induction of labor (IL)/conservative management (CM)/none, i.e., diagnosed-at-birth (DaB)] on maternal stress were tested at 6 years' postbirth. In general, prenatal management protocols of IUGR were efficient in preventing major disabilities; however, 49% of the variance in maternal stress at 6 years' postbirth could be attributed to the child's presenting behavior and to pregnancy management of IUGR condition. Mothers who received CM treatment reported being more stressed by their child's poor emotional adjustment (ps < .01-.002) and distractibility (p < .029), and to have more difficulty in accepting them (p < .01). Prenatal psychological consultation to better handle stress for parents whose fetus is diagnosed with IUGR is recommended, particularly when pregnancy is managed conservatively and familial-educational resources are low.

Our technical ability to diagnose fetal anomalies of the central nervous system by ultrasonography and by fetal magnetic resonance imaging far exceeds our current knowledge of their possible neurodevelopmental implications later in life. This limitation often makes obstetric and clinical decisions very difficult. We retrospectively reviewed the ultrasonographic records of 6220 women who had been followed up at two large medical centers between 1994 and 1999. One hundred and sixty (2.6%) women had abnormal fetal central nervous system findings. The neurodevelopmental outcome of these children was assessed by a telephone interview with the parents. Small cerebellar size was the most frequent anomaly, followed by isolated mild ventriculomegaly and isolated choroid plexus pathology. Suboptimal neurodevelopmental outcome was found in 24% of children with isolated ventriculomegaly and in 9% with choroid plexus pathology. In the group of children with a "small cerebellum," suboptimal neurodevelopment was found in 19%. The measurement of transcerebellar diameter in respect to its developmental implication is, to our knowledge, described here for the first time. We believe that cerebellar measurements and their possible neurocognitive implications should be an integral part of future studies. ( J Child Neurol 2004;19:435-438).

Intrauterine growth retardation plays a significant role in neurodevelopmental outcome. The assessment of general movements during the first 20 weeks is a new method for early detection of brain dysfunction. General movements in 31 infants with asymmetric intrauterine growth retardation and their appropriate for gestational age—matched controls were examined. General movements were scored as normal or abnormal by sequential videotape recordings in the writhing (term to 2 weeks), early fidgety (9—11 weeks), and late fidgety (14—16 weeks) periods. Scores were compared between the groups and correlated with neurodevelopmental outcome at 2 years. The incidence of normal general movements was lower in the intrauterine growth retarded infants than in the controls ( P < .001). Significant correlations were found between general movement quality and neurodevelopmental scores in the intrauterine growth retarded group. The fidgety movements were the most sensitive and specific for prediction of neurologic outcome. The general movement assessment can, therefore, serve as an additional tool for examining the neurologic status of the preterm and term intrauterine growth retarded infant. ( J Child Neurol 2004;19:14—18).

Numerous studies have shown the pathological influence anti-phospholipid antibodies (APLA) have on the physiology of the single neuron as well as the function of the entire human nervous system. The influence is well demonstrated in the antiphospholipid syndrome (APS). This syndrome is characterized by a triad of arterial or venous thrombotic events, recurrent fetal loss and thrombocytopenic purpura. The syndrome exhibits different neurological pathologies such as: chorea, seizures, transverse myelopathy, migraine, cerebral ataxia, hemiballismus and transient global amnesia, which are not fully explained by the procoagulopathic trait of APLA. A study on mice induced with APS demonstrated hyperactive behavior when compared to the control group. The information gathered from these different studies raised the question whether APLA has any part in the etiology of Attention Deficit/Hyperactive Disorder (ADHD) in children.We compared 41 children diagnosed with ADHD to a control of 28 healthy children. Blood drawn from the two groups was screened using ELISA for the presence of anti-cardiolipin antibodies, antiβ2GP antibodies, anti-phosphatidyleserine antibodies and anti-ethanolamine antibodies. The results show no significant difference in the level of antiphospholipid antibodies (APLA) measured between the children diagnosed with ADHD and the control group.

We examined neurological and intellectual outcome of growth-restricted newborns of pregnancies complicated with preeclampsia and without preeclampsia. Seventy-five consecutive growth restricted newborns (5th percentile) were prospectively followed up at 6 months' intervals. Newborns with major congenital malformations and newborns with evident intrauterine viral infection were excluded. At 3 years of age all children had detailed neurological examination and intellectual examination using the Mean developmental index (Stanford Binnet-IQ). Eleven children were born to mother with preeclampsia (ACOG criteria), and 64 were born to mothers without a definite diagnosis of preeclampsia. Gestational age was 34.7 weeks in the preeclamptic group and 37 weeks in the non-preeclamptic group. After adjustment for gestational age, there was no significant difference in the neurological exam score between groups, but the IQ was 85.5 in the preeclamptic group and 96.9 in the non-preeclamptic group (p0.03). We conclude that newborns born growth restricted after pregnancies complicated by preeclampsia have a lower IQ at the age of 3 years compared to growth-restricted babies without preeclampsia.

Objective: To examine long-term behavioral and neurodevelopmental outcome of children born growth restricted and exposed to hypertension in utero at 9 years of age. Methods: Somatic growth and neurocognitive outcomes were evaluated at age 9–10 years of age in 42 children born with intra uterine growth restriction (IUGR) after pregnancies complicated by hypertensive disorder (17 with maternal preeclampsia and 25 after gestational hypertension). This study group was compared to a control group of 78 IUGR children born after normotensive pregnancy. Results: Only weight was found to be significantly lower in the hypertensive-IUGR group, versus the normotensive IUGR children. No significant differences were found in any of the neurocognitive parameters including IQ, school achievements, and neurodevelopmental score at age 9–10 years. Conclusion: IUGR is a well known risk factor for later cognitive difficulties but maternal hypertensive disorder does not seem to add significantly to this risk.

Decreased attention span, hyperactivity, distractibility, and impulsivity are sensitive but non-specific brain functions and behavioral patterns. These expressions of altered functioning should be acknowledged as non-specific, rather than trying to fit them into existing diagnoses. These abnormalities should be viewed in terms of underlying developmental processes and not as components of discrete non-overlapping disorders. The tendency to squeeze a group of symptoms into a diagnostic entity has the potential to lead to a non-accurate diagnosis, a less than successful treatment plan, and has the potential to be of little prognostic value (Berger and Nevo, 2011). The developmental approach can provide predictions as to how characteristics associated with attention change over time, and how multiple risk and protective factors influence these temporal changes. It also has the potential to more readily anticipate associated co-morbid features and disorders (Berger and Nevo, 2011; Visser et al., 2014). Attention Deficit Hyperactivity Disorder (ADHD) seems to be considerably more common than other diagnoses among “double-diagnoses” given to children with developmental dysfunctions. Yet the exact prevalence, neurobiological mechanisms, genetic and epigenetic modifications, diagnostic difficulties and treatment methods have not been clearly identified or quantified. During the last years, the number of publications in this field has grown substantially, but, in part, due to the wide range of interested professionals, these studies have been published in a wide range of journals, sometimes missing some of their “target” populations.

The purpose of this study was to characterize the sleep patterns of children with intrauterine growth retardation, known to be at risk for neurodevelopmental disorders, and seek a possible correlation with behavior, concentration, and attention problems. The sleep patterns of 26 children with intrauterine growth retardation aged 4 to 7 years were compared with those of 47 control children using activity monitors (actigraphs). In addition, data were collected from the parents regarding sleep habits, behavior, concentration, and attention. Children with intrauterine growth retardation aged 4 to 7 years were found to have a tendency toward poorer quality of sleep than their matched controls. This inclination was statistically significant only for one sleep measure, the true sleep time. A tendency toward increased fragmentation of sleep, prolonged waking, and decreased sleep efficiency, although not statistically significant in this study, was demonstrated. Our results showed that 58% of the children with intrauterine growth retardation, compared with 40% of the children in the control group, could be defined as “poor sleepers” (sleep efficiency lower than 90% or three or more waking episodes per night). This disturbed sleep profile is probably an integral part of the neurodevelopmental profile typical of these at-risk children. No significant correlations were found between sleep quality and behavior, concentration, and attention problems. ( J Child Neurol 2002;17:872—876).

In a community-based study of 4,309 children with neurodevelopmental disabilities who were referred to the Institute for Child Development, Tel Aviv, Israel, 62 (1.4%) had macrocephaly (head circumference above the ninety-eighth percentile for age), of whom 42 (1%) had macrocephaly not associated with hydrocephalus. With the exception of neonatal respiratory distress the incidence of perinatal complications was not different from that in other children referred to the Institute for Child Development. In children with developmental disabilities, macrocephaly was a significant risk factor for febrile seizures (odds ratio = 3.1, P < 0.001) and epilepsy (odds ratio = 7.7, P < 0.001), but not for mental retardation (odds ratio = 1.1, P = 0.78) or cerebral palsy (odds ratio = 1.3, P = 0.67). Children with macrocephaly had a high rate of comorbid diagnosis. We conclude that in children with developmental disabilities the presence of macrocephaly even when not associated with hydrocephalus is associated with an increased risk of seizures.

Children with autism spectrum disorder (ASD) are at risk of developing nutritional deviations. Three to six year old children with ASD were compared to their typically developing siblings and to a typically developing age and gender matched control group, in order to evaluate their intake and body mass index. Nutrient intake was compared to the Dietary Reference Intake using three-day diet diaries completed by the parents. The sum percentage of nutritional deficiencies in the ASD group compared to the typical development group was 342.5% (±122.9%) vs. 275.9% (±106.8%), respectively (P=0.026). A trend toward higher deficiency in the ASD group was observed as compared to the sibling group 363% (±122.9%) vs. 283.2% (±94.7%) (P=0.071). A higher body mass index was found in the ASD group compared to their counterparts, despite their nutritional deficiencies. In conclusion, children with ASD are more likely to suffer from nutritional deficiencies despite higher body mass index.

Small for gestational age newborns can later suffer from eating difficulties and slow growth. Nutritional preferences can be influenced by changes in sensory perception of smell and taste. To determine whether these could be detected at birth, the authors examined the different recognition pattern of smell and taste in small for gestational age newborns compared to appropriate for gestational age controls, as expressed by gusto-facial and naso-facial reflexes. The authors performed video analysis of facial expressions of 10 small for gestational age and 12 control newborns exposed to various tastes and smells. No difference in the facial recognition patterns for taste or smell was demonstrated between small for gestational age and controls, except for perception of distilled water. Newborns show recognizable patterns of facial expression in response to taste and smell stimuli. Perception of taste and smell in small for gestational age newborns is not different from controls, as measured by the method of facial recognition.

The study was designed to detect early clinical predictors of developmental outcome in children with intrauterine growth retardation. Eighty-five children with intrauterine growth retardation were followed up prospectively to 3 years of age, using biometric parameters, perinatal risk questionnaires, and neurodevelopmental evaluations. Forty-two children served as controls. A significant difference in neurodevelopmental score at 3 years of age was noted between the intrauterine growth retardation and control groups (P < .001). In the intrauterine growth retardation group, the clinical parameters that most significantly correlated with outcome were cephalization index (head circumference:birthweight ratio), neonatal risk score, and birthweight. The best predictor of 3-year outcome was the cephalization index (P < .01). The children with intrauterine growth retardation with neonatal complications had significantly lower IQ scores (P < .05) and a poorer neurodevelopmental outcome (P < .01) than those without complications. Children with intrauterine growth retardation are at higher risk for developmental disabilities than are controls, especially in the presence of neonatal complications and a high cephalization index. ( J Child Neurol 1999;14:724-727).

Gibberellic acid (GA 3 ) induces the expression of different genes, including chalcone synthase (chs) and gip, in detached petunia corollas. To initiate a study on gibberellin (GA)-signal transduction in this tissue, we examined the effect of agents that inhibit or promote specific steps in signal-transduction pathways. The calcium chelator 1,2-bis(o-aminophenoxy)ethane N,N,N',N'-tetraacetic acid (BAPTA) had no effect on GA-induced gene expression, while the calcium-channel blocker, ruthenium red (RR), inhibited the activation of the genes. The calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) inhibited the induction of chs and gip by the hormone, and its analog, N-(6-aminohexyl)-1-naphthalenesulfonamide hydrochloride (W-5), had lower effect. The activation of chs and gip by GA 3 was completely blocked by the protein phosphatase inhibitor, okadaic acid (OA), and partially inhibited by the protein kinase inhibitor, 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine dihydrochloride (H-7). We suggest that Ca 2+ from intracellular sources, calmodulin and protein dephosphorylation and phosphorylation are involved in GA-induced gene expression in petunia corollas.

The predictive value of abnormal neurological findings on neuroimaging (NI) of children with partial seizures (PS) was studied. The sample comprised 143 children and adolescents with PS from 1979 to 1996. Fifty patients had the following abnormal NI findings: diffuse atrophy and porencephalic cyst (5.6% each), hemiatrophy, tumors, neurocutaneous syndrome brain lesions, and dysgenesis (4.2% each), and arachnoid cyst and hydrocephalus (2.1% each). There were significantly more NI abnormalities among those with simple PS than among the other groups of complex PS or PS with secondary generalization. All cases of porencephalic cyst (n = 8), and hemiatrophy (n = 6) were in the hemiparetic group, all cases of tumor (n = 6) were in the normal group, while most cases of diffuse atrophy were in the mentally retarded group. Patients with abnormal NIs had a significantly earlier age of seizure onset than the others. The chance of finding a treatable abnormality in neuroimaging was 5% for tumors and 2% for arachnoid cysts in the group of patients with PS and normal neurological findings. Neither an abnormality detected in a neurological examination nor the type of seizure are predictive parameters for suggesting the presence of a resectable brain tumor. All patients with newly diagnosed PS should undergo an MRI.

Aim To determine the frequency and natural history of seizures having an onset during the first year of life. Methods A retrospective analysis of the files of all patients treated in the paediatric neurology clinic of our medical centre during 1975–1995. Results Of our 482 patients with seizure onset prior to age 16 years, the first seizure occurred at age 1–12 months in 80 (16.6%). Of those, 38 (48%) had West syndrome and the rest were classified as follows — partial seizures with or without secondary generalization: 19%, generalized tonic seizures: 8.5%, generalized tonic-clonic seizures: 7.5%, myoclonic: 7.5%, unclassified: 7.5%, and mixed-type seizures: 2%. Follow-up was possible in 91% of the patients. Mean follow-up period from seizure onset was 10 years. Of the non-West syndrome patients who were followed, 19 (50%) were still experiencing seizures at follow-up. Eleven of the 15 patients (73%) with partial seizures and four of the 13 patients (31%) with generalized tonic or tonic-clonic seizures had symptomatic seizures. Of the 14 followed patients with partial seizures, 10 (71%) still had seizures at follow-up, as did three (25%) of the 12 followed patients with generalized tonic or tonic-clonic seizures (p = 0.023). Conclusions: The partial seizures were most often symptomatic with unfavourable prognosis, while the generalized seizures were either symptomatic and severe or cryptogenic and rapidly responsive to anti-epileptic drugs with good outcome.

DNA repair is a prime mechanism for preventing DNA damage, mutation, and cancers. Adopting a functional approach, we examined the association with lung cancer risk of an integrated DNA repair score, measured by a panel of three enzymatic DNA repair activities in peripheral blood mononuclear cells. The panel included assays for AP endonuclease 1 (APE1), 8-oxoguanine DNA glycosylase (OGG1), and methylpurine DNA glycosylase (MPG), all of which repair oxidative DNA damage as part of the base excision repair pathways. A blinded population-based case–control study was conducted with 96 patients with lung cancer and 96 control subjects matched by gender, age (±1 year), place of residence, and ethnic group (Jews/non-Jews). The three DNA repair activities were measured, and an integrated DNA repair OMA (OGG1, MPG, and APE1) score was calculated for each individual. Conditional logistic regression analysis revealed that individuals in the lowest tertile of the integrated DNA repair OMA score had an increased risk of lung cancer compared with the highest tertile, with OR = 9.7; 95% confidence interval (CI), 3.1–29.8; P < 0.001, or OR = 5.6; 95% CI, 2.1–15.1; P < 0.001 after cross-validation. These results suggest that pending validation, this DNA repair panel of risk factors may be useful for lung cancer risk assessment, assisting prevention and referral to early detection by technologies such as low-dose computed tomography scanning. Cancer Prev Res; 7(4); 398–406. ©2013 AACR.