Assessment of Research Ethics Knowledge of Pediatricians.

Objectives. To assess knowledge of ethics knowledge among child healthcare professionals. Methods. We translated the Test of Residents' Ethics Knowledge for Pediatrics (TREK-P) in Azeri and administered it to: (i) third-year medical students (n = 21), (ii) pediatrics residents (n = 24), (iii) practicing pediatricians (n = 21), and (iv) fellows (n = 9) who participated in a Fogarty International Center/National Institute of Health (Fogarty/NIH) R25 research ethics education program. The difference in the TREK-P score between the groups and the correlation between the TREK-P score and other factors were evaluated. Results. The fellows scored significantly higher than the other groups (P = .006). There was no significant difference between the other 3 groups. Within a joined group of pediatricians and fellows, previous training on ethics was the only factor that correlated with the higher TREK-P scores (P < .05). Conclusions. The higher scores in fellows support the effectiveness of postgraduate Fogarty/NIH training programs in research ethics.

Evaluating the Decisional Capacity for Informed Consent of Transition age Children to Adolescents in Human Subject Research.

This study aimed to evaluate children's capacity for informed consent. We translated into Azerbaijani language and adapted the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC). We enrolled four healthy groups: children aged 11, 12, and 13 years and adults. We provided the participants with information about the simulated research proposal and a related informed consent form. Subsequently, they were administered the UBACC. The mean total UBACC scores were 11.9 (11-year-olds), 12.7 (12-year-olds), 14.0 (13-year-olds), and 16.0 (adults). The gradual increase in the mean UBACC scores with age suggests the continuous maturation of the capacity to comprehend the informed consent process. There was no specific cutoff age to decide whether the children were competent enough to provide informed consent.

AP4B1-associated hereditary spastic paraplegia: Expansion of clinico-genetic phenotype and geographic range.

BACKGROUND: Hereditary spastic paraplegias (HSP) are a group of neurodegenerative diseases that present with weakness and stiffness in the lower limb muscles and lead to progressive neurological decline. Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to complex HSP. This study aimed to identify causative genetic variants in consanguineous families with HSP from Azerbaijan and Pakistan. METHODS: We performed a thorough clinical and neuroradiological characterization followed by exome sequencing in 7 patients from 3 unrelated families. Segregation analysis was subsequently performed by Sanger sequencing. RESULTS: We describe 7 patients (4 males, 2-31 years of age) with developmental delay and spasticity. Similar to the previously reported cases with AP4B1-associated HSP, cases in the present report besides spasticity in the lower limbs had additional features including microcephaly, facial dysmorphism, infantile hypotonia, and epilepsy. The imaging findings included thin corpus callosum, white matter loss, and ventriculomegaly. CONCLUSION: In this study, we report 7 novel cases of HSP caused by bi-allelic variants in AP4B1 in Azerbaijani and Pakistani families. Our observations will help clinicians observe and compare common and unique clinical features of AP4B1-associated HSP patients, further improving our current understanding of HSP.

Biallelic loss of EMC10 leads to mild to severe intellectual disability.

The endoplasmic reticulum membrane protein complex subunit 10 (EMC10) is a highly conserved protein responsible for the post-translational insertion of tail-anchored membrane proteins into the endoplasmic reticulum in a defined topology. Two biallelic variants in EMC10 have previously been associated with a neurodevelopmental disorder. Utilizing exome sequencing and international data sharing we have identified 10 affected individuals from six independent families with five new biallelic loss-of-function and one previously reported recurrent EMC10 variants. This report expands the molecular and clinical spectrum of EMC10 deficiency, provides a comprehensive dysmorphological assessment and highlights an overlap between the clinical features of EMC10-and EMC1-related disease.

PIGH deficiency can be associated with severe neurodevelopmental and skeletal manifestations.

Phosphatidylinositol Glycan Anchor Biosynthesis class H (PIGH) is an essential player in the glycosylphosphatidylinositol (GPI) synthesis, an anchor for numerous cell membrane-bound proteins. PIGH deficiency is a newly described and rare disorder associated with developmental delay, seizures and behavioral difficulties. Herein, we report three new unrelated families with two different bi-allelic PIGH variants, including one new variant p.(Arg163Trp) which seems associated with a more severe phenotype. The common clinical features in all affected individuals are developmental delay/intellectual disability and hypotonia. Variable clinical features include seizures, autism spectrum disorder, apraxia, severe language delay, dysarthria, feeding difficulties, facial dysmorphisms, microcephaly, strabismus, and musculoskeletal anomalies. The two siblings homozygous for the p.(Arg163Trp) variant have severe symptoms including profound psychomotor retardation, intractable seizures, multiple bone fractures, scoliosis, loss of independent ambulation, and delayed myelination on brain MRI. Serum iron levels were significantly elevated in one individual. All tested individuals with PIGH deficiency had normal alkaline phosphatase and CD16, a GPI-anchored protein (GPI-AP), was found to be decreased by 60% on granulocytes from one individual. This study expands the PIGH deficiency phenotype range toward the severe end of the spectrum with the identification of a novel pathogenic variant.

The Discriminative Ability of the Azeri Version of the Strengths and Difficulties Questionnaire in Outpatient Practice.

In this study we examined the validity of the Azeri version of the Strengths and Difficulties Questionnaire (SDQ). The SDQ was administered to the parents of two samples of 4-16-year-old children: the case group was drawn from children presenting to the psychiatric outpatient service (n = 347) and the comparison group from the pediatric outpatient service (n = 267). The total difficulties score and the scores for each subscale were compared between two groups. The proportion of children with the total difficulties score in the abnormal range was higher in the case group than in the comparison group (74 and 34 %, p < 0.001). The mean difficulties score difference between two groups was significant (mean difference = 6.3, p < 0.001). The Receiver Operating Characteristics analysis showed good discriminative ability for the total difficulties score and difficulties subscales (p < 0.001). SDQ distinguished well between groups.

Spike orientation may predict epileptogenic side across cerebral sulci containing the estimated equivalent dipole.

OBJECTIVE: To evaluate whether the orientation of interictal spikes, localized in major sulci by magnetoencephalography (MEG), predicts the epileptogenic side of the sulcal wall. METHODS: Sixteen epilepsy patients were analyzed in whom equivalent current dipoles (ECDs) of MEG spikes were localized on the central (four patients), interhemispheric (4), or sylvian fissure (8); and the epileptogenic side across the sulci had been confirmed by seizure semiology, structural lesions, or intracranial electroencephalography (EEG). ECD was classified as epileptogenic side or normal side oriented and correlated to the scalp EEG map. RESULTS: All central (n=50) and interhemispheric (n=83) spike ECDs were oriented toward the epileptogenic side at peak latency. In scalp EEG, 91% of the spikes showed radial pattern of broad negativity above the sulcus whereas 9% showed tangential pattern with positive maximum above the epileptogenic side. Sylvian spikes were only found in patients with temporal lobe epilepsy (TLE). In sylvian spikes (n=220), 73% of ECDs were oriented toward the epileptogenic side, whereas 27% were oriented toward the normal side. CONCLUSIONS: In central and interhemispheric spikes, epileptogenic side cortex may be gross surface negative through the sulcal wall to the adjacent gyrus. Inconsistent orientation of the sylvian spikes suggests a complex pattern of spike propagation in TLE. SIGNIFICANCE: ECD orientation of central and interhemispheric spikes in MEG may predict the epileptogenic side.

Evaluation of interhemispheric time difference by magnetoencephalography before and after total callosotomy. Two case reports.

Interhemispheric time difference (ITD) measured by electroencephalography (EEG) and magnetoencephalography (MEG) was compared to seizure outcome after callosotomy. Two patients with frequent drop attacks underwent simultaneous EEG and MEG before and after total callosotomy. ITDs in 30 bilateral synchronized (BS) discharges were calculated independently by EEG and MEG. As minimum transcallosal conduction time was suggested to be approximately 20 msec, BS discharges were classified into five categories according to ITD and side: left- or right-leading long (300 to 80 msec), left- or right-leading moderate (80 to 20 msec), and negligible (<20 msec). In Case 1 before callosotomy, EEG detected 77% negligible and 23% right-leading moderate BS discharges, whereas MEG detected 30% and 63%, respectively. After callosotomy, drop attacks reduced remarkably and EEG and MEG detected no BS discharges. In Case 2 before callosotomy, EEG detected 77% negligible and 23% moderate BS discharges, whereas MEG detected 80% and 20%, respectively. After callosotomy, drop attacks recurred 2 months later and EEG and MEG detected left- and right-leading long BS discharges (63% by EEG and 56% by MEG). MEG detected a large number of BS discharges with moderate ITD before surgery in Case 1, suggesting that the transcallosal pathway was the main pathway for the synchronization, whereas the negligible ITD in Case 2 excludes transcallosal propagation. BS discharges with longer ITD after surgery in Case 2 suggest a persistent poly-synaptic non-transcallosal pathway. MEG with higher spatial resolution than EEG may provide surgical indications for callosotomy.