NGS Nominated CELA1, HSPG2, and KCNK5 as Candidate Genes for Predisposition to Balkan Endemic Nephropathy

Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression leading to terminal renal failure. The results of molecular biological investigations propose that BEN is a multifactorial disease with genetic predisposition to environmental risk agents. Exome sequencing of 22 000 genes with Illumina Nextera Exome Enrichment Kit was performed on 22 DNA samples (11 Bulgarian patients and 11 Serbian patients). Software analysis was performed via NextGene, Provean, and PolyPhen. The frequency of all annotated genetic variants with deleterious/damaging effect was compared with those of European populations. Then we focused on nonannotated variants (with no data available about them and not found in healthy Bulgarian controls). There is no statistically significant difference between annotated variants in BEN patients and European populations. From nonannotated variants with more than 40% frequency in both patients' groups, we nominated 3 genes with possible deleterious/damaging variants-CELA1, HSPG2, and KCNK5. Mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN.

Subjective pubertal timing and health compromising behaviors among on- time Swiss adolescent girls

AIM: The aim of this research is to assess the associations between subjective pubertal timing (SPT) and onset of health-compromising behaviours among girls reporting an on-time objective pubertal timing (OPT). METHODS: Data were drawn from the Swiss SMASH 2002 survey, a self-administered questionnaire study conducted among a nationally representative sample of 7548 adolescents aged 16-20 years. From the 3658 girls in the initial sample, we selected only those (n = 1003) who provided information about SPT and who reported the average age at menarche, namely 13, considering this as an on-time OPT. Bivariate and logistic analyses were conducted to compare the early, on-time and late SPT groups in terms of onset of health-compromising behaviours. RESULTS: A perception of pubertal precocity was associated with sexual intercourse before age 16 [adjusted odds ratio (AOR): 2.10 (1.30-3.37)] and early use of illegal drugs other than cannabis [AOR: 2.55 (1.30-5.02)]. Conversely, girls perceiving their puberty as late were less likely to report intercourse before age 16 [AOR: 0.30 (0.12-0.75)]. CONCLUSION: Faced with an adolescent girl perceiving her puberty as early, the practitioner should investigate the existence of health-compromising behaviours even if her puberty is or was objectively on-time.

Early Detection and Treatment of Psychosis: The Bern Child and Adolescent Psychiatric Perspective

Commonly conceptualized as neurodevelopmental disorders of yet poorly understood aetiology, schizophrenia and other nonorganic psychoses remain one of the most debilitating illnesses with often poor outcome despite all progress in treatment of the manifest disorder. Drawing on the frequent poor outcome of psychosis and its association with the frequently extended periods of untreated first-episode psychosis (FEP) including its prodrome, an early detection and treatment of both the FEP and the preceding at-risk mental state (ARMS) have been increasingly studied. Thereby both approaches are confronted with different problems, for example, treatment engagement in FEP and predictive accuracy in ARMS. They share, however, the problems related to the lack of understanding of developmental, that is, age-related, peculiarities and of the presentation and natural course of their cardinal symptoms in the community. Most research on early detection and intervention in FEP and ARMS is still related to clinical psychiatric samples, and little is known about symptom presentation and burden and help-seeking in the general population related to these experiences. Furthermore, in particular in the early detection of an ARMS, studies often address adolescents and young adults alike without consideration of developmental characteristics, thereby applying risk criteria that have been developed predominately in adults. Combining our earlier experiences described in this paper in child and adolescent, and general psychiatry as well as in both lines of research, that is, on early psychosis and its treatment and on the early detection of psychosis, in particular in its very early states by subjective disturbances in terms of basic symptoms, age-related developmental and epidemiological aspects have therefore been made the focus of our current studies in Bern, thus making our line of research unique

Developmental changes in sleep biology and potential effects on adolescent behavior and caffeine use

Adolescent development includes changes in the biological regulatory processes for the timing of sleep. Circadian rhythm changes and changes to the sleep-pressure system (sleep homeostasis) during adolescence both favor later timing of sleep. These changes, combined with prevailing social pressures, are responsible for most teens sleeping too late and too little; those who sleep least report consuming more caffeine. Although direct research findings are scarce, the likelihood of use and abuse of caffeine-laden products grows across the adolescent years due, in part, to excessive sleepiness

Early adolescent cognitive gains are marked by increased sleep EEG coherence

Although the increases in cognitive capacities of adolescent humans are concurrent with significant cortical restructuring, functional associations between these phenomena are unclear. We examined the association between cortical development, as measured by the sleep EEG, and cognitive performance in a sample of 9/10 year olds followed up 1 to 3 years later. Our cognitive measures included a response inhibition task (Stroop), an executive control task (Trail Making), and a verbal fluency task (FAS). We correlated sleep EEG measures of power and intra-hemispheric coherence at the initial assessment with performance at that assessment. In addition we correlated the rate of change across assessments in sleep EEG measures with the rate of change in performance. We found no correlation between sleep EEG power and performance on cognitive tasks for the initial assessment. In contrast, we found a significant correlation of the rate of change in intra-hemispheric coherence for the sigma band (11 to 16 Hz) with rate of change in performance on the Stroop (r = 0.61; p<0.02) and Trail Making (r =  -0.51; p<0.02) but no association for the FAS. Thus, plastic changes in connectivity (i.e., sleep EEG coherence) were associated with improvement in complex cognitive function.

Success rate of paramedian palatal implants in adolescent and adult orthodontic patients: a retrospective cohort study.

The purpose of this study was to examine the success rate of paramedian palatal Orthosystem first- and second-generation implants used for anchorage in orthodontic treatment in patients treated by one experienced orthodontist. The records of 143 patients (90 female, 53 male, median age: 15.7 years, range: 10.2-50.9) receiving 145 palatal implants of the first or second generation (Orthosystem, Straumann AG, Basel, Switzerland) were examined. All the palatal implants were placed in a paramedian palatal location by three experienced surgeons. Stable implants were orthodontically loaded after a healing period of 3 months. Out of the 145 inserted paramedian palatal implants only seven implants (4.8%) were not considered stable after insertion. All the successfully osseointegrated implants remained stable during orthodontic treatment. Paramedian palatal implants are highly reliable and effective devices to obtain skeletal anchorage for orthodontic treatment. This study has shown that the paramedian location is a good alternative to the median location.

Axial suspension test to assess pre-operative spinal flexibility in patients with adolescent idiopathic scoliosis.

INTRODUCTION An accurate description of the biomechanical behavior of the spine is crucial for the planning of scoliotic surgical correction as well as for the understanding of degenerative spine disorders. The current clinical assessments of spinal mechanics such as side-bending or fulcrum-bending tests rely on the displacement of the spine observed during motion of the patient. Since these tests focused solely on the spinal kinematics without considering mechanical loads, no quantification of the mechanical flexibility of the spine can be provided. METHODS A spinal suspension test (SST) has been developed to simultaneously monitor the force applied on the spine and the induced vertebral displacements. The system relies on cervical elevation of the patient and orthogonal radiographic images are used to measure the position of the vertebras. The system has been used to quantify the spinal flexibility on five AIS patients. RESULTS Based on the SST, the overall spinal flexibility varied between 0.3 °/Nm for the patient with the stiffer curve and 2 °/Nm for the less rigid curve. A linear correlation was observed between the overall spinal flexibility and the change in Cobb angle. In addition, the segmental flexibility calculated for five segments around the apex was 0.13 ± 0.07 °/Nm, which is similar to intra-operative stiffness measurements previously published. CONCLUSIONS In summary, the SST seems suitable to provide pre-operative information on the complex functional behavior and stiffness of spinal segments under physiological loading conditions. Such tools will become increasingly important in the future due to the ever-increasing complexity of the surgical instrumentation and procedures.

Engagement in adolescent career preparation: Social support, personality, and the development of choice decidedness and congruence

This longitudinal panel study investigated predictors and outcomes of active engagement in career preparation among 349 Swiss adolescents from the beginning to the end of eighth grade. Latent variable structural equation modeling was applied. The results showed that engagement in terms of self- and environmental-exploration and active career planning related positively to interindividual increases in career decidedness and choice congruence. More perceived social support, early goal decidedness, and particular personality traits predicted more engagement. Support and personality impacted outcomes only mediated through engagement. Early decidedness and congruence were significant predictors of their respective later levels. Implications for practice are presented.

The New Cockney: New Ethnicities and Adolescent Speech in the Traditional East End of London

The New Cockney provides a sociolinguistic account of speech variation among adolescents in the 'traditional' East End of London. The study takes account of the social and economic upheaval in the area since the 1950s, primarily concentrating on factors such as the immigration of the Bangladeshi community and its effect on the Cockney dialect. By paying attention to the particular, this book contributes to a better understanding of the more general concerns of linguistic variation. With a focus on the interaction and social practices of a group of adolescents attending a youth centre, the study highlights some of the possible mechanisms for language change.

Positive Adolescent Career Development: The Role of Intrinsic and Extrinsic Work Values

This longitudinal study of 268 Swiss adolescents, spanning across 8th grade, investigated the relation of intrinsic and extrinsic work values to positive career development in deciding, planning, and exploring. Results showed that girls reported more intrinsic and fewer extrinsic work values compared with boys. Students with an immigration background reported more extrinsic values than did students of Swiss nationality. When gender, nationality, and scholastic achievement were controlled, more general work value endorsement was a significant predictor of an above-average increase in career development over the course of the school year. Endorsement of more intrinsic but not extrinsic work values was related to positive career development.