Post-transcriptional gene regulation (PTGR) concerns processes involved in the maturation, transport, stability and translation of coding and non-coding RNAs. RNA-binding proteins (RBPs) and ribonucleoproteins coordinate RNA processing and PTGR. The introduction of large-scale quantitative methods, such as next-generation sequencing and modern protein mass spectrometry, has renewed interest in the investigation of PTGR and the protein factors involved at a systems-biology level. Here, we present a census of 1,542 manually curated RBPs that we have analysed for their interactions with different classes of RNA, their evolutionary conservation, their abundance and their tissue-specific expression. Our analysis is a critical step towards the comprehensive characterization of proteins involved in human RNA metabolism.

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A census of human RNA-binding proteins.

Malformations of cerebral cortical development include a wide range of developmental disorders that are common causes of neurodevelopmental delay and epilepsy. In addition, study of these disorders contributes greatly to the understanding of normal brain development and its perturbations. The rapid recent evolution of molecular biology, genetics and imaging has resulted in an explosive increase in our knowledge of cerebral cortex development and in the number and types of malformations of cortical development that have been reported. These advances continue to modify our perception of these malformations. This review addresses recent changes in our perception of these disorders and proposes a modified classification based upon updates in our knowledge of cerebral cortical development.

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A Developmental and Genetic Classification for Malformations of Cortical Development: Update 2012.

Caveolae are submicroscopic, plasma membrane pits that are abundant in many mammalian cell types. The past few years have seen a quantum leap in our understanding of the formation, dynamics and functions of these enigmatic structures. Caveolae have now emerged as vital plasma membrane sensors that can respond to plasma membrane stresses and remodel the extracellular environment. Caveolae at the plasma membrane can be removed by endocytosis to regulate their surface density or can be disassembled and their structural components degraded. Coat proteins, called cavins, work together with caveolins to regulate the formation of caveolae but also have the potential to dynamically transmit signals that originate in caveolae to various cellular destinations. The importance of caveolae as protective elements in the plasma membrane, and as membrane organizers and sensors, is highlighted by links between caveolae dysfunction and human diseases, including muscular dystrophies and cancer.

Caveolae as plasma membrane sensors, protectors and organizers

Autism spectrum disorder is characterized by patterns of delay and deviance in the development of social, communicative, and cognitive skills that arise in the first years of life. Although frequently associated with intellectual disability, this condition is distinctive in its course, impact, and treatment. Autism spectrum disorder has a wide range of syndrome expression and its management presents particular challenges for clinicians. Individuals with an autism spectrum disorder can present for clinical care at any point in development. The multiple developmental and behavioral problems associated with this condition necessitate multidisciplinary care, coordination of services, and advocacy for individuals and their families. Early, sustained intervention and the use of multiple treatment modalities are indicated. J. Am. Acad. Child Adolesc. Psychiatry, 2014;53(2):237–257. Key Words: autism, Practice Parameters, guidelines, developmental disorders, pervasive developmental disorders

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Practice Parameter for the Assessment and Treatment of Children and Adolescents With Autism Spectrum Disorder

Aim The aim of this study was to review systematically the prevalence of headache and migraine in children and adolescents and to study the influence of sex, age, and region of residence on the epidemiology.



Method  We systematically searched the literature in electronic databases to cover the period between 1 January 1990 and 31 December 2007. We assessed and included population-based studies on epidemiology of headache and migraine in children and adolescents if they fulfilled the following criteria: (1) reporting on unselected childhood population; (2) reliable methods of data collection using a questionnaire or face-to-face interviews; (3) using the International Headache Society’s (IHS) criteria (1988 or 2004) for the diagnosis of migraine; and (4) provision of sufficient and explicit data for analysis. We used Excel, Stata, and Confidence Interval Analysis software.



Results  We identified and analysed 50 population-based studies reporting the prevalence of headache and/or migraine in children and adolescents (<20y). The estimated prevalence of headache over periods between 1 month and lifetime in children and adolescents is 58.4% (95% confidence interval [CI] 58.1–58.8). Females are more likely to have headache than males (odds ratio [OR] 1.53, 95% CI 1.48–1.6). The prevalence of migraine over periods between 6 months and lifetime is 7.7% (95% CI 7.6–7.8). Females are more likely than males to have migraine (OR 1.67, 95% CI 1.60–1.75). Regional differences in prevalence of migraine, though statistically significant, may not be of clinical significance. The change in the IHS’s criteria for the diagnosis of migraine was not associated with any significant change in the prevalence of migraine.



Interpretation  This study confirms the global high prevalence of headache and migraine in children and adolescents. Sex, age, and regional differences are evident.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1469-8749.2010.03793.x

Prevalence of headache and migraine in children and adolescents: a systematic review of population-based studies.

Cognitive and behavioral impairments are found more often among epileptic children than among their peers. In this study, we evaluated the anxiety and depression in epileptic children to compare their results with that of a healthy control group and to determine the relationship of anxiety and depression scores to epilepsy-related factors. The State Trait Anxiety Inventory (STAI) and Children's Depression Inventory (CDI) were applied to 35 patients with epilepsy aged 9 to 18 years (mean age 12.9 +/- 2.52 years) and to 35 healthy children who served as the control group. Both study and control groups were divided into two age groups (9 to 11 and 12 to 18 years) to exclude the effect of puberty on anxiety and depression scores. Significant depression and suicidal ideation were determined in the study group. The mean trait anxiety score was significantly higher in the 9- to 11-year age group of epileptic patients than the corresponding control group (35.90 +/- 6.90 and 29.33 +/- 2.84, P < .05). The mean state anxiety score (33.90 +/- 3.90 and 30.40 +/- 6.02, P < .05), trait anxiety score (38.20 +/- 6.84 and 32.20 +/- 3.90, P < .05), and depression score (16.65 +/- 8.32 and 8.15 +/- 3.15, P < .05) were significantly higher in the 12- to 18-year age group of epileptic children than in the control group. Among the epilepsy-related factors, whereas epilepsy duration, seizure frequency, and polytherapy were determined to increase anxiety and depression, age of seizure onset, seizure type, and electroencephalographic findings were not related to anxiety and depression. Symptoms of anxiety and depression are common among epileptic children, especially during puberty. The State Trait Anxiety Inventory and Children's Depression Inventory may be used as a tool to provide information to clinicians.

Relationship of epilepsy-related factors to anxiety and depression scores in epileptic children.

The aim of the study was to compare safety, efficacy and tolerability of risperidone with haloperidol in the treatment of Autistic Disorder (AD). This study was designed as a double-blind, prospective, for a 12-week period. A total of 30 subjects, between the ages of 8 and 18 with AD based on DSM IV criteria, were included in the study. Behavioral Rating Scales were performed by the investigators and the parents. Safety assessment included vital signs, electrocardiogram, electroencephalogram, adverse events, laboratory tests, extrapyramidal symptoms and the side effects. Both treatments were applied in a once daily dosage regimen of 0.01–0.08 mg/kg/day. The reduction from baseline in Ritvo–Freeman Real Life Rating Scale (RF-RLRS), sensory motor (subscale I) and language (subscale V) scores were significant in risperidone group (P < 0.05). Compared to haloperidol, risperidone led to a significantly greater reduction in the Aberrant Behavior Checklist (ABC) and Turgay DSM-IV Pervasive Developmental Disorder (PDD) scale scores (P < 0.05 and P < 0.01). There was a greater increase of prolactin in the risperidone group, while alanine amino transferase (ALT) had further increased in the haloperidol group. Sensory motor behaviors (subscale I) and language at the end of the 12th week, RF-RLRS sensory motor and language subscale scores decreased in the risperidone group further than the other group (P < 0.05). Risperidone was found to be more effective than haloperidol in the treatment of behavioral symptoms, impulsivity, language skills, and impaired social relations in children with AD. These results demonstrated that both drugs were safe and well tolerated in the treatment of AD.

Risperidone versus haloperidol in children and adolescents with AD : a randomized, controlled, double-blind trial.

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near total absence of body fat since birth with predisposition to insulin resistance, diabetes, hypertriglyceridemia, and hepatic steatosis. Three CGL loci, AGPAT2, BSCL2, and CAV1, have been identified previously. Recently, mutations in polymerase I and transcript release factor (PTRF) were reported in five Japanese patients presenting with myopathy and CGL (CGL4). We report novel PTRF mutations and detailed phenotypes of two male and three female patients with CGL4 belonging to two pedigrees of Mexican origin (CGL7100 and CGL178) and one pedigree of Turkish origin (CGL180). All patients had near total loss of body fat and congenital myopathy manifesting as weakness, percussion-induced muscle mounding, and high serum creatine kinase levels. Four of them had hypertriglyceridemia. Three of them had atlantoaxial instability. Two patients belonging to CGL178 pedigree required surgery for pyloric stenosis in the first month of life. None of them had prolonged QT interval on electrocardiography but both siblings belonging to CGL7100 had exercise-induced ventricular arrhythmias. Three of them had mild acanthosis nigricans but had normal glucose tolerance. Two of them had hepatic steatosis. All patients had novel null mutations in PTRF gene. In conclusion, mutations in PTRF result in a novel phenotype that includes generalized lipodystrophy with mild metabolic derangements, myopathy, cardiac arrhythmias, atlantoaxial instability, and pyloric stenosis. It is unclear how mutations in PTRF, which plays an essential role in formation of caveolae, affect a wide variety of tissues resulting in a variable phenotype.

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Congenital generalized lipodystrophy, type 4 (CGL4) associated with myopathy due to novel PTRF mutations.

Adverse effects of antiepileptic drugs on bone mineral density.

Background: The majority of previous studies on headache in children and adolescents have focused mainly on migraine. There is a paucity of population-based studies investigating the prevalence of tension-type headache (TTH). The objectives of the present study were to estimate the prevalence of migraine and TTH in adolescents using the 2004 International Headache Society (IHS) criteria and to determine the sociodemographic and clinical differences between the migraine and TTH.



Methods: Stratified group sampling was used in the present analytic, school-based, cross-sectional study. From the city of Izmir, 2384 students aged 14–18 years were invited to complete a questionnaire.



Results: Migraine was found to be more common than TTH (21.3% vs 5.1%). The prevalence increased considerably to 29.9 and 15%, respectively, when the criteria defining the number and duration of headaches were excluded. All types of headaches were more frequent in female subjects but no significant difference was found in gender between the headache groups (P= 0.073). Headache in temples, number of siblings (more than one sibling), mother’s and father’s education (at least high school graduation) were more commonly seen in students with TTH. Absenteeism rate due to the headache was found to be higher in the migraine group than in the TTH group (P= 0.000).



Conclusions: Migraine and TTH were found to be common types of headaches in adolescents. It was thought that, with the use of modified IHS criteria, the number of undiagnosed patients with headache will decrease.

Eray Dirik

Papers

Relationship of epilepsy-related factors to anxiety and depression scores in epileptic children.

Risperidone versus haloperidol in children and adolescents with AD : a randomized, controlled, double-blind trial.

Congenital generalized lipodystrophy, type 4 (CGL4) associated with myopathy due to novel PTRF mutations.

Adverse effects of antiepileptic drugs on bone mineral density.

Prevalence and clinical findings of migraine and tension-type headache in adolescents.