Dynamic prediction of transition to psychosis using joint modelling.

Considerable research has been conducted seeking risk factors and constructing prediction models for transition to psychosis in individuals at ultra-high risk (UHR). Nearly all such research has only employed baseline predictors, i.e. data collected at the baseline time point, even though longitudinal data on relevant measures such as psychopathology have often been collected at various time points. Dynamic prediction, which is the updating of prediction at a post-baseline assessment using baseline and longitudinal data accumulated up to that assessment, has not been utilized in the UHR context. This study explored the use of dynamic prediction and determined if it could enhance the prediction of frank psychosis onset in UHR individuals. An emerging statistical methodology called joint modelling was used to implement the dynamic prediction. Data from the NEURAPRO study (n = 304 UHR individuals), an intervention study with transition to psychosis study as the primary outcome, were used to investigate dynamic predictors. Compared with the conventional approach of using only baseline predictors, dynamic prediction using joint modelling showed significantly better sensitivity, specificity and likelihood ratios. As dynamic prediction can provide an up-to-date prediction for each individual at each new assessment post entry, it can be a useful tool to help clinicians adjust their prognostic judgements based on the unfolding clinical symptomatology of the patients. This study has shown that a dynamic approach to psychosis prediction using joint modelling has the potential to aid clinicians in making decisions about the provision of timely and personalized treatment to patients concerned.

Omega-3 fatty acid supplementation changes intracellular phospholipase A2 activity and membrane fatty acid profiles in individuals at ultra-high risk for psychosis.

The identification of an ultra-high risk (UHR) profile for psychosis and a greater understanding of its prodrome have led to increasing interest in early intervention to delay or prevent the onset of psychotic illness. In a randomized placebo-controlled trial, we have identified long-chain ω-3 (ω-3) polyunsaturated fatty acid (PUFA) supplementation as potentially useful, as it reduced the rate of transition to psychosis by 22.6% 1 year after baseline in a cohort of 81 young people at UHR of transition to psychosis. However, the mechanisms whereby the ω-3 PUFAs might be neuroprotective are incompletely understood. Here, we report on the effects of ω-3 PUFA supplementation on intracellular phospholipase A2 (inPLA(2)) activity, the main enzymes regulating phospholipid metabolism, as well as on peripheral membrane lipid profiles in the individuals who participated in this randomized placebo-controlled trial. Patients were studied cross-sectionally (n=80) and longitudinally (n=65) before and after a 12-week intervention with 1.2 g per day ω-3 PUFAs or placebo, followed by a 40-week observation period to establish the rates of transition to psychosis. We investigated inPLA(2) and erythrocyte membrane FAs in the treatment groups (ω-3 PUFAs vs placebo) and the outcome groups (psychotic vs non-psychotic). The levels of membrane ω-3 and ω-6 PUFAs and inPLA(2) were significantly related. Some of the significant associations (that is, long-chain ω-6 PUFAs, arachidonic acid) with inPLA(2) activity were in opposite directions in individuals who did (a positive correlation) and who did not (a negative correlation) transition to psychosis. Supplementation with ω-3 PUFA resulted in a significant decrease in inPLA(2) activity. We conclude that ω-3 PUFA supplementation may act by normalizing inPLA(2) activity and δ-6-desaturase-mediated metabolism of ω-3 and ω-6 PUFAs, suggesting their role in neuroprogression of psychosis.

The human ABCG4 gene is regulated by oxysterols and retinoids in monocyte-derived macrophages.

Here we report the induction of gene expression of ABCG4, a member of the ABC transporter subfamily G, from human macrophages by oxysterols and retinoids, agonists of the nuclear receptors LXR and RXR. The cloned ABCG4 transcript has a size of 3.5 kb and contains an open reading frame which encodes a polypeptide of 646 amino acids. Structurally, the putative ABC transporter protein consists of a nucleotide binding fold followed by a cluster of six transmembrane-spanning domains and thus conforms to the group of half-size ABC transporters. Among the human ABC transporter subfamily G members the novel transporter shows highest protein sequence homology and identity to ABCG1 (84 and 72%, respectively). Analysis of the genomic organization demonstrates that the ABCG4 gene is composed of at least 14 exons which extend across a region of 12.6 kb in size on chromosome 11q23.3. Based on its structural features and an LXR/RXR-responsive regulation similar to the cellular lipid export protein ABCA1, we conclude that ABCG4 may be involved in macrophage lipid homeostasis.

[Liposome encapsulation of cystostatic drugs and starch microspheres improve tumor targeting in locoregional therapy. An animal experiment study of CC 531 liver tumor]. / Liposomale Verkapselung von Zytostatika und Stärkemikrosphären verbessern das Tumor-Targeting in der lokoregionären Therapie. Eine tierexperimentelle Studie am CC 531 Lebertumor.

Systemic adjuvant chemotherapy achieves unsatisfactory results for inoperable liver tumors and metastases. Various clinical studies have shown that locoregional chemotherapy increased the survival rate by a few months. The aim of this study was to investigate tumor targeting of the most frequently used cytostatic 5-fluouracil by modifying systemic and locoregional therapy by liposome encapsulation. The tumor concentration of 5-FU encapsulated in SUV-PEG liposomes increases by a factor of 27 in systemic therapy and a factor of 90 in locoregional therapy. The tumor concentration of 5-FU increases by a factor of 8000, if the blood flow is additionally slowed by starch microspheres (Spherex) during locoregional therapy with liposome-encapsulated 5-FU.

Morphological evaluation of osteoblasts cultured on different calcium phosphate ceramics.

The objective of these investigations was to develop an in vitro test system for evaluating novel rapidly resorbable calcium phosphate ceramics of varying composition. Rat bone marrow cells were cultured on the disc-shaped test substrates for 14 days. Five calcium phosphates were examined: R1 CaNaPO4; R1/M2, composed of CaNaPO4 and MgNaPO4; R1/2, composed of CaNaPO4 and Mg2SiO4; R1 + 9% SiO2 consisting of CaNaPO4 and 9% SiO2 (wt%) and R17, Ca2KNa(PO4)2. Two studies were performed. In study I cultures were re-fed every two to three days. In study II the medium was changed daily, and calcium and phosphate concentrations of the medium were determined daily. Specimens were prepared for light microscopy and morphometric evaluation of the cell-covered substrate area, scanning electron microscopy and energy-dispersive X-ray analysis. With all materials tested except for R1/2, an increase of cellular growth was observed after changing the medium daily. Of the different calcium phosphate ceramics tested, R17 and R1/M2 facilitated osteoblast growth and elaboration of extracellular matrix to the highest degree. The inhibition of cell growth encountered with R1 in study I and R1/2 in both studies seemed to be related to a high phosphate-ion release from these materials.

In vitro assessment of the relationship between acoustic properties and bone mass density of the calcaneus by comparison of ultrasound parametric imaging and quantitative computed tomography.

This in vitro study aimed to add new experimental evidence to clarify the relation between acoustic properties of bone and bone mineral density (BMD) of the human calcaneus. Parametric images of normalized broadband ultrasonic attenuation (nBUA) and ultrasound bone velocity (UBV) were compared with quantitative computed tomography (QCT) images of the calcaneus. The experimental protocol was designed to control the different potential sources of error in acoustic measurements, including the shape and thickness of the samples, intervening soft tissues and cortical bone, boundary effects, and variation in location of the regions of interest (ROIs) analyzed by ultrasound and X-ray. The present study was based on bone specimens from calcaneus removed from 15 cadavers (six male and nine female donors ranging from 69 to 89 years of age). Immersion ultrasonic measurements were performed in the through-thickness direction at normal incidence using a pair of focused broad-band 0.5-MHz transducers. QCT of the specimens was performed using standard 10-mm-thick slices with the Cann-Genant calibration standard. Identical, site-matched ROIs were selected for quantitative analysis on the three images. The pattern of acoustic parameters was similar to that of BMD with QCT. The relationships between nBUA and BMD (r2 = 0.75), between UBV and BMD (r2 = 0.88) and between nBUA and UBV (r2 = 0.84) were highly significant (p < 10(-4). From this study, it appears that ultrasound parameters as measured with current transmission techniques reflect mainly bone quantity and only reflect microarchitecture to a small extent and that BUA and UBV reflect the same bone property.

Nutritional status, dietary intake and disease patterns in rural Hereros, Kavangos and Bushmen in South West Africa/Namibia.

A survey of Hereros, Kavangos and Bushmen living in the rural districts of South West Africa/Namibia was undertaken in order to assess their dietary intakes, nutritional status and disease patterns. The results showed that Hereros were taller and heavier, with the highest incidence of obesity (15-30%) and hypertension. Their diet consisted chiefly of refined maize meal supplemented with sour milk, and their blood lipid levels were generally lower than Western standards. The diet of Kavangos, based on homeground millet supplemented with fish and fresh vegetables, was better balanced. However, malnutrition was more common particularly in hospital patients where 40% had infective disease. Finally, the diet of Bushmen was extremely poor consisting of whatever was available (generally maize meal) and excessive use of home-brewed alcohol. The majority were malnourished and 73% of those hospitalised had tuberculosis. The blood lipid levels of Bushmen and Kavangos were exceptionally 'favourable' by Western standards but associated with chronic malnutrition. The survival of Bushmen in modern society is a matter of grave concern.

[Peri-implantation enzymes and mineralization in bone tissue after implantation of bioactive vitroceramic material--a method for biomaterial testing for hard tissue substitutes. 2. Results of studies of vitroceramics and their modification by the admixture of metal oxides]. / Untersuchungen periimplantärer Enzymaktivitäten und der periimplantären Mineralisation im Knochengewebe nach Implantation bioaktiver vitrokeramischer Materialien--Eine Methode der Biomaterialprüfung für den Hartgewebeersatz. Teil 2: Ergebnisse der Untersuchungen von Vitrokeramen und deren Modifizierungen durch Zusatz von Metalloxiden.

The activities of the alkaline and the acid bone phosphatases as well as the concentrations of calcium and phosphorus were measured in the periimplantal tissue of the rat femur bone after implantation of the vitroceramic Ap 40, the metal oxide stabilized vitroceramics Ap 40 A and Ap 40 Z, as well titanium after 2, 10, and 15 weeks. The incorporation of the vitroceramic Ap 40 turns out like a primary bone fracture healing. The implants Ap 40 A and Ap 40 Z are a compromise with a higher stability and the osteogenesis induced effect is preserved, but is belated in contrast to Ap 40.

[Surface reactivity of enosseous implanted bio-glass ceramics at varying lengths of implantation]. / Untersuchungen zur Oberflächenreaktivität enossal implantierter Biovitrokeramik nach unterschiedlicher Implantationsdauer.

Chemical and structural surface changes at enosseous bioglass-ceramic-implants (Ap 40) were investigated by means of electron microprobe after an implantation period of 4 to 52 weeks. An intimate bonding between regenerated bone and bioglass-ceramic surface was evident at points already after 4 weeks. Initial degradation processes at implant surface came to a standstill after 12th week. A calcium and phosphorus rich layer of great importance for implant stability and biocompatibility was formed immediately contacting the bone. This surface layer had a thickness of nearly 25 micrometers -- 30 micrometers at 12 weeks and remains unchanged up to 52 weeks. The registered calcium and phosphorus impulse rate (cps) is equal to that of neighbouring bone. Chemical similarity of implant surface makes bioglass-ceramic Ap 40 a suitable biomaterial for durable bone replacement.

[Comparative scanning electron microscopical investigation of the bond between bone and different alloplastic implant materials (author's transl)]. / Vergleichende rasterelektronenmikroskopische Untersuchung der Grenzflächen zwischen Knochen und verschiedenen alloplastischen Implantatmaterialien.

The traditional alloplastic implant materials and their applications are represented and are investigated in a comparative scanning electron microscopical study between bone and alloplastic. Provable are clear in "bio-vitroceramic Ap 40" compounds to the bone in the scanning electron microscopical photo-contrary to titanium, tantalum and teflon.

Self-rated imagery and encoding strategies in visual memory.

The value of self-rated vividness of imagery in predicting performance was investigated, taking into account the mnemonic strategies utilized among subjects performing a visual-memory task. Subjects classified as 'good' or 'poor' imagers, according to their scores in the Vividness of Visual Imagery Questionnaire (VVIQ; Marks, 1972), were to detect as rapidly as possible differences between pairs of similar pictures presented consecutively. No coding instructions were given and the mnemonic strategies used were analysed by studying subjective reports and objective performance measurements. The results indicated that the subjects utilized two main strategies--a detail or an image strategy. The detail strategy was the more efficient. In accordance with a previous study (Berger & Gaunitz, 1977), it was found that the VVIQ did not discriminate between performance by 'good' and 'poor' imagers. However, among subjects who used the image strategy, 'good' imagers performed more rapidly than 'poor' imagers. Self-rated imagery may then have some value in predicting performance among individuals shown to have utilized an image strategy.

[Pathogenesis of osteopathy caused by anticonvulsives (author's transl)]. / Zur Atiologie der Osteopathie durch Antikonvulsiva

After a short survey of the recent suggestions of the pathogenesis of osteopathy caused by therapy with anticonvulsives it is demonstrated in the light of 3 case reports that 1. A vitamin D-sensible rickets, which is only due to abnormal living conditions, can develop in severely cerebral-damaged persons if there is no specific vitamin D administration. 2. An "antiepileptic rickets" is spontaneously reversible if the anticonvulsive therapy is stopped. 3. An enzymatic induction due to anticonvulsives is also detectable in the light of morphologic hepatic changes (biopsy, electron microscopy). Hence it follows that there are demands for a specific control of all patients treated with anticonvulsives. It is recommended to carry out a rickets prevention for a selected patient group.