The measurement of maternal plasma corticotropin-releasing factor (CRF) and CRF-binding protein improves the early prediction of preeclampsia

In the present study we measured maternal plasma concentrations of two placental neurohormones, corticotropin-releasing factor (CRF) and CRF-binding protein (CRF-BP), in 58 at-risk pregnant women consecutively enrolled between 28 and 29 wk of pregnancy to evaluate whether their evaluation may predict third trimester-onset preeclampsia ( PE). The statistical significance was assessed by t test. The cut-off points for defining altered CRF and CRF-BP levels for prediction of PE were chosen by receiving operator characteristics curve analysis, and the probability of developing PE was calculated for several combinations of hormone testing results. CRF and CRF-BP levels were significantly ( both P < 0.0001) higher and lower, respectively, in the patients (n = 20) who later developed PE than in those who did not present PE at follow-up. CRF at the cut-off 425.95 pmol/liter achieved a sensitivity of 94.8% and a specificity of 96.9%, whereas CRF-BP at the cut-off 125.8 nmol/liter combined a sensitivity of 92.5% and a specificity of 82.5% as single markers for prediction of PE. The probability of PE was 34.5% in the whole study population, 93.75% when both CRF and CRF-BP levels were changed, and 0% if both hormone markers were unaltered. The measurement of CRF and CRF-BP levels may add significant prognostic information for predicting PE in at-risk pregnant women.

Therapeutic patents for the treatment of pre-eclampsia

Pre-eclampsia (PE) is a pregnancy-specific syndrome that is a principal cause of maternal morbidity and mortality, accounting for almost 15% of pregnancy-associated deaths. In its mild form, PE most commonly presents with the features of maternal hypertension and proteinuria but can swiftly and unpredictably become severe with many extensive and life-threatening complications. The diverse symptoms of PE have made it a difficult disease not only to define, but also to identify a causative agent for the symptoms. It has therefore proved difficult to develop specific drugs that can be used to manage the condition. This review examines the patent literature to reveal current findings that exhibit the potential to target the effects of PE with the aim of either preventing or altering the course of this life-threatening disease of pregnancy.

Effect of dietary fatty acid composition on inositol-, choline- and ethanolamine-phospholipids of mammary tissue and erythrocytes in the rat

The present study investigated the effect of feeding maize-oil, olive-oil and fish-oil diets, from weaning to adulthood, on rat mammary tissue and erythrocyte phospholipid fatty acid compositions. Effects of diet on the relative proportions of membrane phospholipids in the two tissues were also investigated. Mammary tissue phosphatidylinositol (PI) fatty acids were unaltered by diet, but differences in phosphatidylethanolamine (PE) and, to a lesser extent, phosphatidylcholine (PC) fractions were found between animals fed on different diets from weaning. Differences observed were those expected from the dietary fatty acids fed; n-6 fatty acids were found in greatest amounts in maize-oil-fed rats, n-9 in olive-oil-fed rats, and n-3 in fish-oil-fed rats. In erythrocytes the relative susceptibilities of the individual phospholipids to dietary modification were: PE > PC > PI, but enrichment with n-9 and n-3 fatty acids was not observed in olive-oil- and fish-oil-fed animals and in PC and PE significantly greater amounts of saturated fatty acids were found when animals fed on olive oil or fish oil were compared with maize-oil-fed animals. The polyunsaturated:saturated fatty acid ratios of PE and PC fractions were significantly lower in olive-oil- and fish-oil-fed animals. No differences in the relative proportions of phospholipid classes were found between the three dietary groups. It is suggested that differences in erythrocyte fatty acid composition may reflect dietary-induced changes in membrane cholesterol content and may form part of a homoeostatic response the aim of which is to maintain normal erythrocyte membrane fluidity. The resistance of mammary tissue PI fatty acids to dietary modification suggests that alteration of PI fatty acids is unlikely to underlie effects of dietary fat on mammary tumour incidence rates.

Time is of the essence: a selective review of the fall and rise of brief therapy research

For compelling reasons of equity and the advance of public health, brief psychotherapy has become the dominant format in both practice and research. One consequence of this is the apparent decline of a distinct stream of brief therapy research. However, much of the agenda formerly identified with that research stream is of increasing importance to the field. Time is indeed of the essence in current psychotherapy research. For example, factors conducive to the time efficiency of brief psychodynamic therapy have been described recently. The important question ‘How much therapy is enough?’ has been addressed by studies inspired by the dose-response analysis of Howard and colleagues. The value of ultra-brief interventions has been examined. These issues are considered in a selective review, drawing in particular on the work of the Sheffield/Leeds psychotherapy of depression research group. This research treats the number of treatment sessions as an independent variable, thereby providing a causal analysis of the dose-response relationship over a range from two to 16 sessions, illuminated by a comparative analysis of change processes in treatments of different durations. Its results enable some specification of the extent and nature of incremental benefit derived from additional sessions in the psychotherapy of depression.

Simulating current global river runoff with a global hydrological model: model revisions, validation, and sensitivity analysis

Global hydrological models (GHMs) model the land surface hydrologic dynamics of continental-scale river basins. Here we describe one such GHM, the Macro-scale - Probability-Distributed Moisture model.09 (Mac-PDM.09). The model has undergone a number of revisions since it was last applied in the hydrological literature. This paper serves to provide a detailed description of the latest version of the model. The main revisions include the following: (1) the ability for the model to be run for n repetitions, which provides more robust estimates of extreme hydrological behaviour, (2) the ability of the model to use a gridded field of coefficient of variation (CV) of daily rainfall for the stochastic disaggregation of monthly precipitation to daily precipitation, and (3) the model can now be forced with daily input climate data as well as monthly input climate data. We demonstrate the effects that each of these three revisions has on simulated runoff relative to before the revisions were applied. Importantly, we show that when Mac-PDM.09 is forced with monthly input data, it results in a negative runoff bias relative to when daily forcings are applied, for regions of the globe where the day-to-day variability in relative humidity is high. The runoff bias can be up to - 80% for a small selection of catchments but the absolute magnitude of the bias may be small. As such, we recommend future applications of Mac-PDM.09 that use monthly climate forcings acknowledge the bias as a limitation of the model. The performance of Mac-PDM.09 is evaluated by validating simulated runoff against observed runoff for 50 catchments. We also present a sensitivity analysis that demonstrates that simulated runoff is considerably more sensitive to method of PE calculation than to perturbations in soil moisture and field capacity parameters.

Syncytiotrophoblast extracellular vesicles from pre-eclampsia placentas differentially affect platelet function

Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes of maternal mortality worldwide. The pathophysiology of PE remains unclear however its underlying cause originates from the placenta and manifests as raised blood pressure, proteinuria, vascular or systemic inflammation and hypercoagulation in the mother. Women who develop PE are also at significantly higher risk of subsequently developing cardiovascular (CV) disease. In PE, the failing endoplasmic reticulum, oxidative and inflammatory stressed syncytiotrophoblast layer of the placenta sheds increased numbers of syncytiotrophoblast extracellular vesicles (STBEV) into the maternal circulation. Platelet reactivity, size and concentration are also known to be altered in some women who develop PE, although the underlying reasons for this have not been determined. In this study we show that STBEV from disease free placenta isolated ex vivo by dual placental perfusion associate rapidly with platelets. We provide evidence that STBEV isolated from normal placentas cause platelet activation and that this is increased with STBEV from PE pregnancies. Furthermore, treatment of platelets with aspirin, currently prescribed for women at high risk of PE to reduce platelet aggregation, also inhibits STBEV-induced reversible aggregation of washed platelets. Increased platelet reactivity as a result of exposure to PE placenta derived STBEVs correlates with increased thrombotic risk associated with PE. These observations establish a possible direct link between the clotting disturbances of PE and dysfunction of the placenta, as well as the known increased risk of thromboembolism associated with this condition.

Fractionated crystallization and fractionated melting of confined PEO microdomains in PB-b-PEO and PE-b-PEO diblock copolymers

The confined crystallization of poly(ethylene oxide) (PEO) in predominantly spherical microdomains formed by several diblock copolymers was studied and compared. Two polybutadiene-b-poly(ethylene oxide) diblock copolymers were prepared by sequential anionic polymerization (with approximately 90 and 80 wt % polybutadiene (PB)). These were compared to equivalent samples after catalytic hydrogenation that produced double crystalline polyethylene-b-poly(ethylene oxide) diblock copolymers. Both systems are segregated into microdomains as indicated by small-angle X-ray scattering (SAXS) experiments performed in the melt and at lower temperatures. However, the PB-b-PEO systems exhibited a higher degree of order in the melt. A predominantly spherical morphology of PEO in a PB or a PE matrix was observed by both SAXS and transmission electron microscopy, although a possibly mixed morphology (spheres and cylinders) was formed when the PEO composition was close to the cylinder-sphere domain transitional composition as indicated by SAXS. Differential scanning calorimetry experiments showed that a fractionated crystallization process for the PEO occurred in all samples, indicating that the PE cannot nucleate PEO in these diblock copolymers. A novel result was the observation of a subsequent fractionated melting that reflected the crystallization process. Sequential isothermal crystallization experiments allowed us to thermally separate at least three different crystallization and melting peaks for the PEO microdomains. The lowest melting point fraction was the most important in terms of quantity and corresponded to the crystallization of isolated PEO spheres (or cylinders) that were either superficially or homogeneously nucleated. This was confirmed by Avrami index values of approximately 1. The isothermal crystallization results indicate that the PE matrix restricts the crystallization of the covalently bonded PEO to a higher degree compared to PB.

A follow-up study of characteristics of young people that dropout and continue psychotherapy: service implications for a clinic in the community

Background: The paper reports the findings from a follow-up study of the factors that contribute to whether young people dropout or continue once-weekly psychotherapy at a voluntary sector psychotherapy service for young people aged 12 to 21 years. Method: The study uses data from an ongoing audit of the psychotherapy service that started in 1993; 882 young people were included in the study. Premature termination of treatment was defined as dropping out before the 21st session. Continuation in treatment was defined as remaining in therapy after 20 sessions. Measures and areas of interest used in the study include diagnostic measures, the Youth Self Report Form and Young Adult Self Report Form, demographic characteristics and treatment related information. Results: Young people who continued in treatment were more likely to be older, have anxieties about sexual and relationship issues and have higher scores on self-reported anxiety-depression. Young people who dropped out of treatment were more likely to be younger, have higher self-reported delinquency scores, have a diagnosis of hyperactivity-conduct disorder and be homeless. Conclusions: The study of treatment termination has demonstrated the value of service audit and has led to a significant change in clinical practice.

Effects of psychotherapy for anxiety in children and adolescents: a meta-analytic review

This paper provides a comprehensive quantitative review of high quality randomized controlled trials of psychological therapies for anxiety disorders in children and young people. Using a systematic search for randomized controlled trials which included a control condition and reported data suitable for meta-analysis, 55 studies were included. Eligible studies were rated for methodological quality and outcome data were extracted and analyzed using standard methods. Trial quality was variable, many studies were underpowered and adverse effects were rarely assessed; however, quality ratings were higher for more recently published studies. Most trials evaluated cognitive behavior therapy or behavior therapy and most recruited both children and adolescents. Psychological therapy for anxiety in children and young people was moderately effective overall, but effect sizes were small to medium when psychological therapy was compared to an active control condition. The effect size for non-CBT interventions was not significant. Parental involvement in therapy was not associated with differential effectiveness. Treatment targeted at specific anxiety disorders, individual psychotherapy, and psychotherapy with older children and adolescents had effect sizes which were larger than effect sizes for treatments targeting a range of anxiety disorders, group psychotherapy, and psychotherapy with younger children. Few studies included an effective follow-up. Future studies should follow CONSORT reporting standards, be adequately powered, and assess follow-up. Research trials are unlikely to address all important clinical questions around treatment delivery. Thus, careful assessment and formulation will remain an essential part of successful psychological treatment for anxiety in children and young people.

Pollen ultrastructure in anther cultures of Datura innoxia. III. Incomplete microspore division

During the microspore division in Datura innoxia, the mitotic spindle is oriented in planes both perpendicular (PE) and oblique (OB) to the spore wall against which the nucleus is situated. However, irrespective of polarity, the usual type of hemispherical wall is laid down at cytokinesis and isolates the generative cell from the rest of the pollen grain (type A). In PE spores the vegetative nucleus initially occupies a central position in the pollen grain, whereas in OB spores the vegetative nucleus lies at the periphery of the grain close to the generative cell. In anther cultures initiated just before the microspore division is due to take place, no marked change can be observed in either orientation or symmetry of the mitotic spindle when the spores divide. In some, however, cytokinesis is disrupted and deposition of the hemispherical wall arrested. In the absence of a complete wall, differentiation of the generative cell cannot take place and binucleate pollen grains are formed having 2 vegetative-type nuclei (type B). The 2 nuclei in the B pollens are always situated against the pollen-grain wall, suggesting that the disruption phenomenon is related to the OB spores. The incomplete wall always makes contact with the intine on the intine-side of the spindle. Wall material may be represented merely as short stubs projecting out from the intine into the cytoplasm, in which event the 2 nuclei lie close to each other and are separated by only a narrow zone of cytoplasm. In other grains the wall is partially developed between the nuclei and terminates at varying distances from the tonoplast; in these, the nuclei are separated by a wider zone of cytoplasm. The significance of these binucleate grains in pollen embryogenesis is discussed.

Complete filling of zeolite frameworks with polyalkynes formed in situ by transition-metal ion catalysts

We report the use of transition-metal-exchanged zeolites as media for the catalytic formation and encapsulation of both polyethyne and polypropyne, and computer modeling studies on the composites so formed. Alkyne gas was absorbed into the pores of zeolite Y (Faujasite) exchanged with transition-metal cations [Fe(II), Co(II), Cu(II), Ni(II), and Zn(II)]. Ni(II) and Zn(II) were found to be the most efficient for the production of poly-ynes. These cations were also found to be effective in polymer generation when exchanged in zeolites mordenite and beta. The resulting powdered samples were characterized by FTIR, Raman, diffuse reflectance electronic spectroscopy, TEM, and elemental analysis, revealing, nearly complete loading of the zeolite channels for the majority of the samples. Based on the experimental carbon content, we have derived the percentage of channel filling, and the proportion of the channels containing a single polymer chain for mordenite. Experimentally, the channels for Y are close to complete filling for polyethyne (PE) and polypropyne (PP), and this is also true for polyethyne in mordenite. Computer modeling studies using Cerius2 show that the channels of mordenite can only accept a single polymer chain of PP, in which case these channels are also completely filled.

Structural study of BSA/poly(ethylene glycol) lipid conjugate complexes

In this work we report the structural characteristics of bovine serum albumin/poly(ethylene glycol) lipid conjugate (BSA/PEG(2000)-PE) complexes under physiological conditions (37 degrees C and pH 7.4) for particular fractions of BSA to PEG-lipid concentration, CBSA/C-PEG2000-PE. Ultraviolet fluorescence spectroscopy (UV) results shown that PEG(2000)-PE is associated to BSA, leading to;protein unfolding for fixed C-BSA = 0.01 wt % and variable C-PEG2000-PE = 0.0015-0.6 wt %. Tryptophan groups on the BSA surface are in contact with the PEG-lipid at C-PEG2000-PE = 0.0015 wt %, while they are exposed to water at C-PEG2000-PE (>)0.0015 wt %. Dynamic and static light scattering (DLS and SLS) and small-angle neutron scattering (SANS) point out the existence of individual BSAIPEG-lipid complexes in the system for fixed C-BSA = 1 wt % and variable C-PEG2000-PE = 0.15-2 wt %. DLS shows that there is only one BSA molecule per protein/PEG-lipid complex, while SLS shows that the PEG-lipid associates to the BSA without promoting aggregation between adjacent protein/ polymer-lipid conjugate complexes. SANS was used to show that BSA/PEG(2000)-PE complexes adopt an oblate ellipsoidal shape. Partially unfolded BSA is contained in the core of the oblate ellipsoid, which is surrounded by an external shell containing the PEG(2000)-PE.