THE LANGUAGE-HANDICAPPED CHILD—Coordinated Evaluation by Physicians and Educators

Seventy children were studied during 1959 in a special school program because of major language problems. A team of medical and educational personnel studied each child during a ten-day school enrollment. The results of the medical and educational studies were of great value in establishing the correct diagnosis and devising a suitable educational program for the children.     

Computational Cardiology—A New Discipline of Translational Research

正Over the past two decades,improved diagnosis,pharmaceutical therapies,and interventional strategies have impressively improved the armamentarium of modern cardiologists in the?ght against the most incident and lethal diseases:heart failure,ischemic heart disease,and arrhythmia.The innovations     

Adolescents’ Use of Care for Behavioral and Emotional Problems: Types,Trends, and Determinants

Objective

While adolescents use various types of care for behavioral and emotional problems, evidence on age trends and determinants per type is scarce. We aimed to assess use of care by adolescents because of behavioral and emotional problems, overall and by type, and its determinants, for ages 10–19 years.

Methods

We obtained longitudinal data on 2,230 adolescents during ages 10–19 from four measurements regarding use of general care and specialized care (youth social care and mental healthcare) in the preceding 6 months, the Child Behavior Checklist (CBCL) and Youth Self-Report, and child and family characteristics. We analyzed data by multilevel logistic regression.

Results

Overall rates of use increased from 20.1% at age 10/11 to 32.2% at age 19: general care was used most. At age 10/11 use was higher among boys, at age 19 among girls. Use of general care increased for both genders, whereas use of specialized care increased among girls but decreased among boys. This differential change was associated with CBCL externalizing and internalizing problems, school problems, family socioeconomic status, and parental divorce. Preceding CBCL problems predicted more use: most for mental health care and least for general care. Moreover, general care was used more frequently by low and medium socioeconomic status families, with odds ratios (95%-confidence intervals): 1.52 (1.23;1.88) and 1.40 (1.17;1.67); youth social care in case of parental divorce, 2.07 (1.36;3.17); and of special education, 2.66 (1.78;3.95); and mental healthcare in case of special education, 2.66 (1.60;4.51).

Discussion

Adolescents with behavioral and emotional problems use general care most frequently. Overall use increases with age. Determinants of use vary per type.     

Health-Related Quality of Life in Adolescent Chronotypes—A Model for the Effects of Sleep Problems,Sleep-Related Cognitions,and Self-efficacy

In adolescence, the circadian preference shifts toward eveningness orientation. Eveningness seems to be negatively correlated with quality of life. The present study investigates influencing factors of this association and proposes a model for the mediating effects of sleep, sleep-related cognitions, and self-efficacy according to chronotype. The sample comprised N?=?280 adolescents (172 girls) aged 14–16 yrs (mean?=?15.19, SD?=?.76). Circadian preference, health-related quality of life (HRQoL), sleep disturbances, sleep-related dysfunctional cognitions, and general perceived self-efficacy were assessed online. Morning-orientated adolescents reported significantly higher HRQoL and less insomnia symptoms compared with evening-oriented chronotypes. In the total sample, insomnia symptoms mediated the relationship of chronotype and HRQoL. The strongest predictor of HRQoL in evening types was the degree of sleep-related dysfunctional cognitions. HRQoL in morning types was most strongly predicted by general self-efficacy, i.e., the global confidence in coping abilities. The findings support a negative relationship of eveningness and HRQoL in adolescents. Insomnia symptoms were identified to be mediating factors in this relationship. The influence of the mediating factors on HRQoL differed between morning and evening types. The model provides implications of how to enhance HRQoL in adolescents according to their circadian preference. (Author correspondence: karolin.roeser@uni-wuerzburg.de)     

Methodology and Problems of Protein‐Ligand Docking: Case Study of Dihydroorotate Dehydrogenase,Thymidine Kinase,and Phosphodiesterase 4

Abstract

The docking methodology was applied to three different therapeutically interesting enzymes: human dihydroorotate dehydrogenase (DHODH), Herpes simplex virus type I thymidine kinase (HSV1 TK) and human phosphodiesterase 4 (PDE4). Programs FlexX, AutoDock and DOCK where used. The three targets represent three distinct cases. For DHODH and HSV1 TK, the binding modes of substrate and inhibitors within the active site are known, while the binding orientation of cAMP within PDE4 has been solely hypothesized. Active site of DHODH is mainly hydrophobic and the binding mode of the inhibitor brequinar was used as a template for evaluating the docking strategies. The presence of cofactors revealed to be crucial for the definition of the docking site. The HSV1 TK active site is small and polar and contains crystal water molecules and ATP. Docking of thymidine and aciclovir (ACV) within the active site was analyzed by keeping or removing water molecules. It showed the crucial role of water in predicting the binding of pyrimidines and purines. The crystal structure of PDE4 contains magnesium and zinc cations as well as catalytic water molecule but no ligand. Several docking experiments of cAMP and rolipram were performed and the results showed clear‐cut dependence between the ligand orientation and the presence of metals in the active site. All three cases show specific problems of the docking methodology, depending on the character of the active site.     

The Cellular Mechanism of Orcadian Rhythms–A View on Evidence,Hypotheses and Problems

A stable period length is a characteristic property of circadian oscillations. The question about whether higher frequency oscillators (0.5–8 hr) contribute to or establish the stable circadian periodicity cannot be answered at present. A sequential coupling of quantal subcycles appears possible on the basis of known “ultradian” oscillations. There is, however, no supporting evidence for such a concept. Phase response curves of the circadian clock derived from various perturbing pulses allow qualitative conclusions concerning the perturbed clock process. Deductions from computer simulations also allow conclusions about the phase of this oscillatory process.

The distinction between processes (a) essential to the clock mechanism, (b) maintaining and controlling the clock (inputs) and (c) depending on the clock (outputs) on the basis of “oscillatory” and “change of ? or τ after perturbation” seems to be useful but not stringent. Protein synthesis may be an essential or input process. Oscillatory changes of this process may be due to periodic translational control or RNA-supply. Circadian changes in protein concentration and/or activity may depend on periodic synthesis, proteolysis, covalent modifications or aggregations. Specific essential proteins have not been identified conclusively. The large overlap between the group of agents and treatments that phase shift the clock and the group that induces stress proteins suggest that the latter may play a role in the controlling (input) or essential domain.

The role of membranes in the clock mechanism is not clear: concepts assuming an essential function are based on circumstantial evidence. The membrane potential as well as Ca²⁺ may be involved in either input or essential function. Ca²⁺ -calmodulin may also be important as concluded from inhibitor experiments. It is tempting to assume that a calmodulin-dependent kinase is part of a periodic protein phosphorylation process, yet it is not clear whether the periodic protein phosphorylation that has been observed is essential or is just another output process.     

Biosynthesis,isolation, purification and separation of nivalenol,fusarenone — X and zearalenone

Fusarium, graminearum KF 370 isolate is able to simultaneous biosynthesis of three toxic metabolites, namely: fusarenone-X (FUS), nivalenol (NIV) and zearalenone (F-2). After metabolites extraction with methanol — water (3:1) and defatting with n-heptane toxins were partitioned into chloroform layer. Purification of the? compounds was performed on Celite 545 — charcoal — Aluminiumoxid 90 column then metabolites were separated on Kieselgel 60 (200–300 mesh) column with developing solvent chloroform — methanol. This way FUS, NIV and F-2 were obtained as crystalline or high purity standards.