Slobodan Sekulic

International Epidemiology of Child and Adolescent Psychopathology II: Integration and Applications of Dimensional Findings From 44 Societies

OBJECTIVE To build on Achenbach, Rescorla, and Ivanova (2012) by (a) reporting new international findings for parent, teacher, and self-ratings on the Child Behavior Checklist, Youth Self-Report, and Teachers Report Form; (b) testing the fit of syndrome models to new data from 17 societies, including previously underrepresented regions; (c) testing effects of society, gender, and age in 44 societies by integrating new and previous data; (d) testing cross-society correlations between mean item ratings; (e) describing the construction of multisociety norms; (f) illustrating clinical applications. METHOD Confirmatory factor analyses (CFAs) of parent, teacher, and self-ratings, performed separately for each society; tests of societal, gender, and age effects on dimensional syndrome scales, DSM-oriented scales, Internalizing, Externalizing, and Total Problems scales; tests of agreement between low, medium, and high ratings of problem items across societies. RESULTS CFAs supported the tested syndrome models in all societies according to the primary fit index (Root Mean Square Error of Approximation [RMSEA]), but less consistently according to other indices; effect sizes were small-to-medium for societal differences in scale scores, but very small for gender, age, and interactions with society; items received similarly low, medium, or high ratings in different societies; problem scores from 44 societies fit three sets of multisociety norms. CONCLUSIONS Statistically derived syndrome models fit parent, teacher, and self-ratings when tested individually in all 44 societies according to RMSEAs (but less consistently according to other indices). Small to medium differences in scale scores among societies supported the use of low-, medium-, and high-scoring norms in clinical assessment of individual children.

Spectral and Fractal Analysis of Cerebellar Activity After Single and Repeated Brain Injury

The cerebellum, even when not directly damaged, is potentially interesting for understanding the adaptive responses to brain injury. Cerebellar electrocortical activity (ECoG) in rats was studied using spectral and fractal analysis after single and repeated unilateral injury of the parietal cortex. Local field potentials of cerebellar paravermal cortex were recorded before brain injury, in the acute phase (up to 2.5 hours) after a first injury of anesthetized rats, and then before and after second, third, and, in some cases, fourth injury. Relative gamma power (32.1–128.0 Hz) and fractal dimension of ECoGs were temporarily increased after the first injury. However, there was a permanent mild increase in gamma activity and a mild increase in the fractal dimension of cerebellar activity as a chronic change after repeated remote brain injury. There was a negative linear correlation between the normalized difference in fractal dimensions and normalized difference in gamma powers of cerebellar activity only in the case of repeated brain injury. This is the first study showing that correlation between the parameters of spectral and fractal analyses of cerebellar activity can discriminate between single and repeated brain injuries, and is, therefore, a promising approach for identifying specific pathophysiological states.

Social competence among well-functioning adolescents with epilepsy

PURPOSE The aims of the study were to measure the social competence of well-functioning adolescents with epilepsy and compare it with that of their healthy peers as well as to analyze the effects of epilepsy-related variables on the social competence. METHODS Ninety well-functioning adolescents with epilepsy 12-19years of age were compared with healthy controls using the Achenbach Youth Self-Report Questionnaire measures of social competence. Within the group with epilepsy, the impact of duration of epilepsy, etiology, seizure frequency, seizure type, and antiepileptic drugs (AEDs) (monotherapy or polytherapy) on the above measures was also determined. RESULTS Twenty-five (27.8%) adolescents with epilepsy obtained Total Competence T scores in the clinical range, as opposed to only two (3.3%) of the healthy adolescents. There were statistically significant differences in the Activity and Social subscales and Total Competence T score between the group with epilepsy and the control group (p<0.05). Comparing T scores for epilepsy-related variables in the group with epilepsy, we found that there were statistically significant differences in all the social competence subscales regarding the seizure control and seizure types. No significant differences were obtained for other epilepsy-related variables: duration of epilepsy, onset of epilepsy, etiology, and AEDs. CONCLUSION Our results indicate that adolescents with epilepsy are less active in clubs, socialize less with their friends, and have a poorer school performance compared with their healthy peers. This study shows that adolescents with epilepsy are at an increased risk of having difficulties in social competence.

Ultrasonographic observations of the maturation of basic movements in guinea pig fetuses

Ultrasonography has not previously been used for studying fetal movements in precocial rodents. The objective of this study was to ultrasonographically determine the sequence of the appearance of basic movements in a guinea pig fetus. The research included eight guinea pig females carrying one fetus each. Fetal movements were observed for 10 minutes each day, from the 25th to 38th day of gestation. The time and sequence of the appearance of movements was observed as follows: whole body flexion (mean 27.6 SD ± 1.68), whole body extension (mean 28.1 SD ± 1.12), head flexion (mean 28.1 SD ± 1.80), head extension (mean 30.5 SD ± 2.67) forelimbs flexion (mean 30.5 SD ± 2.32), forelimbs extension (mean 30.7 SD ± 1.84), trunk rotation (mean 31.9 SD ± 2.23), forelimbs alternating flexion and extension (mean 32.1 SD ± 2.1), hind limbs extension (mean 32.2 SD ± 3.2), hind limbs flexion (mean 32.4 SD ± 3.16), and hind limbs alternating flexion and extension (mean 33.5 SD ± 2.39). The identical sequences of basic movement appearances in guinea pigs, sheep, and rats suggest that the rostrocaudal gradient of basic movement appearance could be a general developmental pattern in mammalian species.

Decreased expression of the righting reflex and locomotor movements in breech-presenting newborns in the first days of life

AIM To investigate differences between the infants born in occipital and breech presentation relative to the passive and active motility. METHOD A prospective study was conducted in the period from 2006 to 2007 at the Department of Obstetrics and Gynecology in Novi Sad. Subjects were 50 breech-presenting and 87 occipital-presenting term newborns delivered by elective cesarean section following a regular course of pregnancy, without fetal, newborn, and the pregnant female disease. Outcome measures were popliteal angle; extension of the hip-joint; ventral flexion and dorsal extension in the axis; spontaneous displacement; crawling reflex; righting reaction in vertical and sitting positions; righting reaction in horizontal suspension, the automatic walking investigated on the second and fourth day of life. RESULTS Except for righting reaction in horizontal suspension, the newborns from breech presentation had a significantly lower score for all investigated parameters of active movements at the first and second examination. There was no difference between occipital and breech-group relative to the ventral flexion and dorsal extension in the axis. The popliteal angle was significantly increased, whereas the extension in the hip joint was significantly decreased in the breech group. CONCLUSIONS Investigations showed a significantly decreased expression of active movements in the breech group, which cannot be explained only by postural deformities.

Breech presentation and the cornual-fundal location of the placenta

Aim To investigate the association of cornual-fundal location of the placenta and breech presentation at term delivery. Methods This study was conducted at the Department of Obstetrics and Gynecology, Novi Sad, in 2011. The inclusion criteria were delivery at ≥37 weeks of gestation, singleton gestation, and cornual-fundal location of the placenta determined by ultrasonography at ≥37 weeks of gestation when 3/4 or more of the placenta was in the cornual-fundal region. Results Out of 2750 ultrasound examinations performed, 143 showed cornual-fundal location of the placenta (frequency 5.2%). Eighty six cases had cephalic presentation (60.14%) and 57 (39.86%) had breech presentation. Of the remaining cases with non- cornual-fundal location, 2585 had cephalic presentation and 22 (0.84%) had breech presentation. The difference in the frequency of breech presentation between the cornual-fundal and non-cornual-fundal groups was significant (χ2 = 77.78, P < 0.001). Conclusion Cornual-fundal location of the placenta may be an important clue in resolving the etiology of a number of cases of breech presentation at term delivery.

Probability of breech presentation and its significance

Existing data related to the probability of breech presentation suggest that the breech presentation is a consequence of mere filling of the intrauterine space, with the same probability of breech and cephalic presentation. As a consequence, group of cephalic presenting fetuses is heterogenous. Some fetuses randomly assume the cephalic presentation while others assume cephalic presentation ‘intentionally’ for a reason. Before comparing breech and cephalic presenting fetuses/newborns, bias should be eliminated by subtracting from the cephalic-presenting group the number of fetuses/newborns that is identical with the number of breech-presenting fetuses/newborns with identical characteristics. The subtracted group should be added to the breech-presenting group before comparison with the remaining cephalic-presenting fetuses/newborns. The comparison should be corrected for the gestational age and according to data that are not influenced by delivery. Data suggest that the physiological process that accounts for 92% of cephalic-presenting human fetuses at delivery should be sought from the 25th gestational week onwards.

Appearance of fetal pain could be associated with maturation of the mesodiencephalic structures

Fetal pain remains a controversial subject both in terms of recognizing its existence and the time-frame within which it appears. This article investigates the hypothesis that pain perception during development is not related to any determined structures of the central nervous system (CNS), on the contrary, the process of perception could be made with any structure satisfying conditions that the perception of pain is the organization, identification, and interpretation of sensory information in order to represent and understand the environment. According to this definition, chronic decerebrate and decorticate experimental animals, anencephalic, and hydranencephalic patients demonstrate that the basic, most general, appropriate interaction with the environment can be achieved with a functional mesodiencephalon (brain stem, and diencephalon) as the hierarchically highest structure of the CNS during development. In intact fetuses, this structure shows signs of sufficient maturation starting from the 15th week of gestation. Bearing in mind the dominant role of the reticular formation of the brain stem, which is marked by a wide divergence of afferent information, a sense of pain transmitted through it is diffuse and can dominate the overall perception of the fetus. The threshold for tactile stimuli is lower at earlier stages of gestation. The pain inhibition mechanisms are not sufficiently developed during intrauterine development, which is another factor that leads to increased intensity of pain in the fetus. As a conclusion it could be proposed that the fetus is exposed to rudimentary painful stimuli starting from the 15th gestation week and that it is extremely sensitive to painful stimuli.

Vitamin C Depletion in Prenatal Guinea Pigs as a Model of Lissencephaly Type II

Humans and guinea pigs are unable to produce vitamin C, with deficiency resulting in a well-known disorder of collagen synthesis. Pial basement membrane structure preservation is essential in the proper migration of neurons. In our study, intrauterine deprivation of vitamin C in guinea pig fetuses led to a collagen synthesis disorder, weakness, and finally a breach of pial basement membrane. We found excessive migration of the external germinal layer cells into the subarachnoid space of the cerebellum through defects in the pial basement membrane. The changes ranged from focal rupture of pial basement membranes to their complete disintegration. The loss of proper folia formation resulted in macroscopically visible flattening of the cerebellar surface. Different grades of dysplastic changes in the folia of the cerebellar cortex were observed in 2 experimental groups assigned different limits to mark the time of commencement and duration of vitamin C deprivation. The most severe form of dysplastic changes was characterized by marked irregularity of the cerebellar cortex similar to that in lissencephaly type II. Thus, prenatal vitamin C deficiency represents a novel animal model to study the effects of collagen synthesis on development of breaches in the pial basement membrane, disordered migration of neurons, dysplasia of cerebellar cortex, and the pathogenesis of lissencephaly.

Early physical and motor development of mouse offspring exposed to valproic acid throughout intrauterine development

Clinical research has identified developmental delay and physical malformations in children prenatally exposed to the antiepileptic drug (AED) valproic acid (VPA). However, the early signs of neurodevelopmental deficits, their evolution during postnatal development and growth, and the dose effects of VPA are not well understood. The present study aimed to examine the influence of maternal exposure to a wide dose range (50, 100, 200 and 400mg/kg/day) of VPA during breeding and gestation on early physical and neuromotor development in mice offspring. Body weight gain, eye opening, the surface righting reflex (SRR) and tail suspension test (TST) were examined in the offspring at postnatal days 5, 10 and 15. We observed that: (1) all tested doses of VPA reduced the body weight of the offspring and the timing of eye opening; (2) offspring exposed to VPA displayed immature forms of righting and required more time to complete the SRR; (3) latency for the first immobilization in the TST is shorter in offspring exposed to higher doses of VPA; however, mice in all groups exposed to VPA exhibited atypical changes in this parameter during the examined period of maturation; (4) irregularities in swinging and curling activities were observed in animals exposed to higher doses of VPA. This study points to delayed somatic development and postponed maturation of the motor system in all of the offspring prenatally exposed to VPA, with stronger effects observed at higher doses. The results implicate that the strategy of continuous monitoring of general health and achievements in motor milestones during the early postnatal development in prenatally VPA-exposed offspring, irrespectively of the dose applied, could help to recognize early developmental irregularities.