Which schizophrenic patients improve under work therapy, which ones don't?

This investigation is part of a multicenter study, where only small effects and no superiority compared to creative ergotherapy was found for four weeks of inpatient work therapy. The criteria were three scales of the Osnabrück-Working Capabilities Profile (O-AFP) assessing basic learning ability, social communication ability and adaptation at the work place. The goal of this investigation is to identify subgroups of patients within the work therapy group, which differ in their course of ability level during the intervention. Three subgroups were identified for each scale. Subgroups with improvements comprise 24 % (learning ability) and 15 % (social communication) of the sample. Adaptation level decreases in a group of 9 % of the patients. The remaining clusters show constancy of abilities at different levels. Comparison of the clusters with neurocognitive, symptom and motivational variables shows that for learning ability mainly neurocognitive variables yield salient differences, whereas for social communication abilities, symptoms and motivation, together with a specific aspect of memory, seem to be characteristic. Only positive symptoms are related to adaptation. Also, there are hints for variables that specifically characterize patients with improvement of ability level. The discussion deals with issues of assessment and prognosis in rehabilitation, contributions to the neurocognitive theory of schizophrenia and to the development of person-centered interventions.     

An in vitro larval immersion microassay for identifying and characterizing candidate acaricides

We have optimized a larval immersion microassay (LIM) that offers superior sensitivity, flexibility to accommodate multiple formulations, and a robust capability for rapidly screening many compounds with a minimal requirement of test article for evaluation. Dose-response studies were conducted for representative members from the organophosphate, pyrethroid, pyrazole, carbamate, macrocyclic lactone, and formamidine chemistries against Amblyomma americanum (L.). Time-response experiments revealed that permethrin was the most rapid acting, whereas fipronil had the slowest speed-of-kill against A. americanum. Comparison of drug susceptibility profiles between multiple ixodid ticks suggests that A. americanum is an effective model for predicting compound potency against Boophilus spp. in this bioassay. The LIM is suitable for the identification and characterization of active molecules from small- and medium-sized compound or natural product libraries, and it can be a useful tool to prioritize molecules for further in vivo testing in animal models.     

Structural basis for the role in protein folding of conserved proline-rich regions in cytochromes P450

The sequence PPGPXPXPXXGN is highly conserved in some cytochromes P450 across species from humans to plants. Within species, however, this specific sequence is not conserved although a proline-rich sequence is present. In CYP2C proteins, mutagenesis of the prolines and glycine in the PPGPXPXP part of the sequence results in less efficient assembly of native P450 molecules, but those molecules that are formed properly have specific activities similar to wild type suggesting that this region plays a role in folding of the protein. Further, the pattern of requirements for prolines was consistent with a left-handed polyproline II (PPII) helix structure in the PPGP segment. The recent determinations of the structures of CYP2C proteins permit a reinterpretation of these earlier experimental studies. In CYP2C5, the PPGPXPXP part of the sequence is in a left-handed polyproline II-like sequence with a 90 degrees bend at the glycine residue. The PXPXXGN part forms a hairpin structure with the remaining sequence protruding at a right angle. The structure forms tertiary interactions with protein segments centered on Tyr-61, Phe-219, and Tyr-376. van der Waals contacts of the rings of prolines with those of the equally highly conserved tyrosine residues may be particularly important. The proper positioning of the N-terminal segment containing Tyr-61 and the C-terminal segment containing Tyr-376 by interactions with the proline-rich region may be important for proper folding because these residues are in loops extending from four strands of a beta-sheet structure. A schematic model of the sequential folding interactions is presented, and although speculative, it is proposed that constraints required for the folding of a hydrophobic knob that will be inserted into the membrane contribute to the high conservation of the PPGPXPXPXXGN sequence in a subset of cytochromes P450.     

Astrocyte-specific overexpression of insulin-like growth factor-I promotes brain overgrowth and glial fibrillary acidic protein expression

Insulin-like growth factor-I (IGF-I) is widely expressed in the central nervous system (CNS). Whereas during normal development IGF-I is expressed predominantly by neurons and to a much lesser degree by glial cells, its expression in astrocytes, and often in microglia, is increased during and/or after variety of CNS injuries. Recently we have generated a new line of IGF-I Tg mice, called IGF-I(Ast/Tet-Off) Tg mice, in which IGF-I transgene is expressed specifically in astrocytes and is tightly controlled by the tetracycline analog doxycycline. In this study we examined whether IGF-I derived from astrocytes is capable of promoting neural cell growth during development. When the IGF-I transgene is allowed to be expressed, IGF-I(Ast/Tet-Off) Tg mice exhibit markedly increases in 1) brain weight; 2) brain DNA and protein abundance; and 3) number of neurons, oligodendrocytes, and astrocytes, as well as myelination, findings similar to those observed in our other lines of Tg mice that express IGF-I transgene predominantly in neurons. Unlike Tg mice with neuron-specific IGF-I expression, which manifest marked increases in the concentrations of oligodendrocyte/myelin-specific proteins, however, IGF-I(Ast/Tet-Off) Tg mice exhibit an increase in the concentration of glial fibrillary acidic protein, an astrocyte-specific protein. Furthermore, when transgene expression is blunted, brain overgrowth in IGF-I(Ast/Tet-Off) Tg mice ceases. Our data indicate that astrocyte-derived IGF-I is capable of promoting neural cells growth in vivo. Our data also suggest that IGF-I's actions in CNS depend in part on the location of its expression and cellular microenvironment and that continuous presence of IGF-I expression is necessary for brain overgrowth.     

Localization of white matter volume increase in autism and developmental language disorder

Increased brain volume in autism appears to be driven mainly by an unexplained white matter enlargement, and we have reported a similar phenomenon in developmental language disorder (DLD). Localization of this enlargement would strongly guide research into its cause, tissue basis, and functional implications. We utilized a white matter parcellation technique that divides cerebral white matter into an outer zone containing the radiate compartment and an inner zone containing sagittal and bridging system compartments. In both high-functioning autism and DLD, enlargement localized to the radiate white matter (all lobes in autism, all but parietal in DLD), whereas inner zone white matter compartments showed no volume differences from controls. Furthermore, in both autism and DLD, later or longer-myelinating regions showed greater volume increases over controls. Neither group showed cerebral cortex, corpus callosum, or internal capsule volume differences from control. Radiate white matter myelinates later than deep white matter; this pattern of enlargement thus is consistent with striking postnatal head circumference percentile increases reported in autism. These findings suggest an ongoing postnatal process in both autism and DLD that is probably intrinsic to white matter, that primarily affects intrahemispheric and corticocortical connections, and that places these two disorders on the same spectrum.     

Considering culture,complementary medicine,and spirituality in pediatrics

Whether or not it is apparent, cultural and spiritual diversity exist in many clinical encounters, both with patients and with colleagues. These issues may cloud other concerns, contribute to inadequate or misleading communication, and affect lifestyle and therapeutic choices. Given the rapid rise in complementary therapies and the growing diversity in North America, the challenges of providing sensitive, compassionate, comprehensive care are compounded. Reflecting on the ways cultural backgrounds, religious beliefs and complementary medicine affect physicians, colleagues and patients may enrich, clarify, deepen, and improve the effectiveness of our clinical practice. The cases presented here offer an opportunity for role playing and reflection to support this process.     

Early prophylactic inhaled beclomethasone in infants less than 1250 g for the prevention of chronic lung disease

OBJECTIVE:

Inflammation plays an important role in the development of chronic lung disease (CLD), which has become a major cause of morbidity in surviving infants less than 1250 g at birth. The authors hypothesized that the progression of this inflammation and, therefore, the establishment of CLD would be decreased with the use of early prophylactic inhaled corticosteroids. Short, and long term respiratory and neurodevelopmental outcomes were also examined.

DESIGN:

A double-blind, randomized placebo controlled trial.

SETTING:

Level-III neonatal intensive care unit.

POPULATION STUDIED:

Sixty infants less than 1250 g at birth, diagnosed with respiratory distress syndrome and requiring ventilatory support at 72 h of age were enrolled in the study.

INTERVENTION:

Infants enrolled received either placebo or beclomethasone diproprionate by a metered dose inhaler, which was used in-line with the ventilator circuit while the infant was ventilated and then via a spacer until 28 days of age.

RESULTS:

Thirty infants were given beclomethasone and 30 were given placebo. There were two deaths in each group. Among the surviving infants, the frequency of moderate-to-severe CLD was 17% in each study group. Mean time to extubation was not different for beclomethasone compared with placebo at 16.4 and 12.5 days (P=0.12), respectively. The requirement for intravenous corticosteroids was lower in the beclomethasone-treated group (RR 0.67, 95% CI 0.43 to 1.04), although this difference was not statistically significant. The incidence of growth failure, infection and intraventricular hemmorhage did not differ between the two groups. Long term outcomes were not different with respect to the incidence of respiratory re-admissions, cerebral palsy, developmental delay, blindness or deafness.

CONCLUSIONS:

Early treatment with inhaled beclomethasone diproprionate did not reduce the incidence of CLD or decrease the duration of mechanical ventilation. The decrease in intravenous corticosteroid use was not statistically significant. Long term outcome was not affected.     

Concurrent validity of a weight-bearing activity questionnaire in prepubertal and pubertal girls and boys

OBJECTIVE: The purpose of this study was to evaluate the current validity of an interviewer-administered physical activity questionnaire against measurement of physical activity from vertical body accelerometer movements in prepubertal and pubertal children. METHODS: The Weight Bearing Activity Questionnaire for Kids (WBAQK) is an interviewer-administered questionnaire with a recall over 7 days and developed to assess weight-bearing activity in pre-pubertal and pubertal children. The Caltrac(TM) accelerometer was worn for 4-5 days (including 1 weekend day). Thirty-seven schoolgirls and 35 schoolboys participated, with a mean age of 11.2 0.3 years and 12.1 0.2 years, respectively. RESULTS: Weight-Bearing Score (WBS) and Metabolic Score (MS) derived from the WBAQK were significantly and positively related to the score of the Caltrac(TM). Weight-Bearing Score showed higher correlations in both boys (0.59) and girls (0.53) and slightly better compared to MS (0.54 and 0.35). The classification of boys and girls into high and low activity groups resulted also in a better agreement of WBS (71-72%) than of MS (60-67%) with Caltrac(TM). CONCLUSIONS: We conclude that the amount of weight-bearing activity can be estimated with the interviewer-administered WBAQK in boys and girls between 8 and 14 years of age.