Weighing as part of your care: a feasibility study exploring the re-introduction of weight measurements during pregnancy as part of routine antenatal care.

BACKGROUND: The UK does not currently have guidelines on gestational weight gain owing to gaps in the evidence base. Reintroducing routine weighing of women throughout pregnancy would begin to provide the evidence needed to fill this gap. The aim of this research was to re-introduce measurement of weight at each routine antenatal appointment in a small scale study, in order to determine the feasibility and acceptability of implementing the practice on a larger scale. METHODS: A feasibility study, incorporating quantitative and qualitative components, was conducted in one antenatal hospital clinic and with one community midwifery team. Thirty-eight pregnant women were recruited at their 20 week anomaly scan appointment and weighed at their appointments throughout the rest of their pregnancy; five participated in a telephone interview at approximately 37 weeks gestation. Data were collected on: numbers consenting to be weighed, reasons for declining to be weighed and number of weight measurements recorded. Qualitative interviews were used to explore acceptability of the practice to pregnant women. RESULTS: Overall, 79.2% (38 out of 48) of those approached consented to being weighed throughout pregnancy; of the 10 who declined, three cited not wanting to be weighed. In the interviews, women discussed routine weighing as a positive experience, described several benefits of weighing and indicated they would like more information about weight during pregnancy. No major barriers to the integration of a weight measurement into routine antenatal appointments were encountered. Completion of the weight record sheets that were inserted into women's handheld notes varied between staff: of the 26 sheets recovered from handheld notes, only 3 (11.5%) had no weights recorded, 17 (65.4%) had between one and three weights recorded and six (23.1%) had more than 4 weights recorded. CONCLUSIONS: In this feasibility study, routine weighing was acceptable to pregnant women. No barriers that would inhibit re-introduction of weighing women throughout pregnancy into standard antenatal care were encountered. Implementation of routine weighing during pregnancy on a larger scale should be considered as it may have benefits for women in the short and long-term, particularly with regard to informing appropriate gestational weight gain guidelines in the UK.

Recurrent Sinopulmonary Infections in a Patient Whose HIV Masked Common Variable Immunodeficiency.

It is generally accepted that persons infected with human immunodeficiency virus (HIV) are at an increased risk of infection due to direct destruction of CD4+ lymphocytes and subsequently impaired cell-mediated immunity. Typically, HIV infection is associated with immunoglobulin elevations, but quantitative deficiencies in immunoglobulins have also been rarely described. We present an unusual case of common variable immunodeficiency (CVID) in a HIV-positive patient with recurrent severe respiratory infections. We review epidemiology, clinical presentation, and treatment of primary immunoglobulin deficiency. We also review the relationship between immunoglobulin deficiency and HIV and highlight the importance of recognizing the coexistence of two distinct immunodeficiency syndromes.

First demonstration of velocity selective recording from the pig vagus using a nerve cuff shows respiration afferents.

Neural interfaces have great potential to treat disease and disability by modulating the electrical signals within the nervous system. However, whilst neural stimulation is a well-established technique, current neural interfaces are limited by poor recording ability. Low signal amplitudes necessitate the use of highly invasive techniques that divide or penetrate the nerve, and as such are unsuitable for chronic implantation. In this paper, we present the first application of the velocity selective recording technique to the detection of respiration activity in the vagus nerve, which is involved with treatments for epilepsy, depression, and rheumatoid arthritis. Further, we show this using a chronically implantable interface that does not divide the nerve. We also validate our recording setup using electrical stimulation and we present an analysis of the recorded signal amplitudes. The recording interface was formed from a cuff containing ten electrodes implanted around the intact right vagus nerve of a Danish Landrace pig. Nine differential amplifiers were connected to adjacent electrodes, and the resulting signals were processed to discriminate neural activity based on conduction velocity. Despite the average single channel signal-to-noise ratio of - 5.8 dB, it was possible to observe distinct action potentials travelling in both directions along the nerve. Further, contrary to expectation given the low signal-to-noise ratio, we have shown that it was possible to identify afferent neural activity that encoded respiration. The significance of this is the demonstration of a chronically implantable method for neural recording, a result that will transform the capabilities of future neuroprostheses.

Evaluation of the predictive value of placental vascularisation indices derived from 3-Dimensional power Doppler whole placental volume scanning for prediction of pre-eclampsia: A systematic review and meta-analysis.

Pre-eclampsia remains a leading cause of maternal and fetal morbidity and mortality. This systematic review aims to evaluate the ability of placental vascularisation indices (PVIs) derived from 3D power Doppler whole placental volume scanning to predict early, late and any-onset pre-eclampsia (PE). The following databases were searched: MEDLINE, EMBASE and Web of Science. Studies selected for inclusion measured PVIs: Vascularisation Index (%) (VI) and/or Flow Index (FI) and/or Vascularisation Flow Index (VFI) derived from 3D power Doppler whole placental volume scanning via Virtual Organ Computer-aided Analysis (VOCAL) technique prior to diagnosis of PE. A total of 667 records were screened with five eligible studies included. A narrative review of all studies was undertaken and three studies with sufficient data were included in a meta-analysis. This review, the first of its kind to evaluate the predictive value of PVIs for PE, reports significantly lower first trimester PVIs across a range of studies in women who develop PE. Mean differences in vascularisation indices in PE and non-PE pregnancies were: VI -2.93% (95% CI -5.84,-0.01), FR -2.83 (95% CI -3.97,-1.69) and VFI -0.93 (95% CI -1.6,-0.25), respectively. While only two studies reported sensitivity and specificity data, VI and VFI most accurately predicted early onset PE, and VFI predicted PE in high risk women. Further research is required to validate these findings in different study populations and to examine the performance of PVIs within combined screening models for PE.

Deletion of creB in Aspergillus oryzae increases secreted hydrolytic enzyme activity.

Aspergillus oryzae has been used in the food and beverage industry for centuries, and industrial strains have been produced by multiple rounds of selection. Targeted gene deletion technology is particularly useful for strain improvement in such strains, particularly when they do not have a well-characterized meiotic cycle. Phenotypes of an Aspergillus nidulans strain null for the CreB deubiquitinating enzyme include effects on growth and repression, including increased activity levels of various enzymes. We show that Aspergillus oryzae contains a functional homologue of the CreB deubiquitinating enzyme and that a null strain shows increased activity levels of industrially important secreted enzymes, including cellulases, xylanases, amylases, and proteases, as well as alleviated inhibition of spore germination on glucose medium. Reverse transcription-quantitative PCR (RT-qPCR) analysis showed that the increased levels of enzyme activity in both Aspergillus nidulans and Aspergillus oryzae are mirrored at the transcript level, indicating transcriptional regulation. We report that Aspergillus oryzae DAR3699, originally isolated from soy fermentation, has a similar phenotype to that of a creB deletion mutant of the RIB40 strain, and it contains a mutation in the creB gene. Collectively, the results for Aspergillus oryzae, Aspergillus nidulans, Trichoderma reesei, and Penicillium decumbens show that deletion of creB may be broadly useful in diverse fungi for increasing production of a variety of enzymes.

Passive acoustic detection of closed-circuit underwater breathing apparatus in an operational port environment.

Divers constitute a potential threat to waterside infrastructures. Active diver detection sonars are available commercially but present some shortcomings, particularly in highly reverberant environments. This has led to research on passive sonar for diver detection. Passive detection of open-circuit UBA (underwater breathing apparatus) has been demonstrated. This letter reports on the detection of a diver wearing closed-circuit UBA (rebreather) in an operational harbor. Beamforming is applied to a passive array of 10 hydrophones in a pseudo-random linear arrangement. Experimental results are presented demonstrating detection of the rebreather at ranges up to 120 m and are validated by GPS ground truth.

Double-blind, controlled phase II study of a 5-HT6 receptor antagonist, SB-742457, in Alzheimer's disease.

BACKGROUND: This randomized, double-blind, placebo-controlled study investigated the efficacy and tolerability of the 5-HT6 receptor antagonist, SB-742457, in subjects with mild-to-moderate probable Alzheimer's disease (AD). METHODS: Participating subjects had a Mini-Mental State Examination (MMSE) score of 12 to 26 after a 4-week, single-blind, placebo run-in phase, and were randomized (2:1:1:2) to receive placebo, SB-742457 5 mg, 15 mg, or 35 mg once daily for 24 weeks. Coprimary efficacy endpoints were the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+) score and change from baseline in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score at Week 24, in the intent-to-treat (ITT) population. A model-based design provided 90% power to detect a linear trend in treatment response across increasing doses and > or =90% power to compare SB-742457 35 mg with placebo. RESULTS: 371 subjects were randomized. In the ITT population (n=357), linear trend analysis at Week 24 suggested a dose response for CIBIC+ with a mean slope of -0.05 points/5-mg dose increase (95% confidence interval [CI]: -0.09, -0.01; p=0.016). The dose response slope for change from baseline in ADAS-Cog was -0.22 points/5-mg dose increase (95% CI: -0.45, 0.01; p=0.059). The adjusted mean treatment difference from placebo at Week 24 for SB-742457 35 mg (-0.31) was significant on CIBIC+ (95% CI: -0.62, -0.00; p=0.047) but non-significant on ADAS-Cog (-1.28 [95% CI: -2.96, 0.40]; p=0.135). Adverse events occurred in 24-37% in the SB-742457 groups vs 29% for placebo; 11-16% discontinued SB-742457 vs 15% for placebo. COMMENTS: SB-742457 was generally safe and well tolerated and may be efficacious in AD.

Can radiation-induced apoptosis be modulated by inhibitors of energy metabolism?

PURPOSE: To determine the effect of the inhibitors of energy metabolism, 2-deoxyglucose (2DG) and sodium azide, on radiation-induced apoptosis. MATERIALS AND METHODS: Radiation-induced apoptosis was determined in U937 monocytic leukaemia cells exposed to energy inhibitors post-irradiation. Apoptosis was scored microscopically using morphological criteria. Glycolysis was determined by assessing glucose consumption and lactate production. Adenine nucleotide levels were measured using a luciferase assay after enzymatic conversion to ATP. Respiration was measured using a Clark-type oxygen electrode. RESULTS: In addition to their apoptosis-inducing properties, both 2DG and azide modified post-irradiation apoptosis. 2DG induced apoptotic radiosensitization after exposure to lower concentrations (5 mM, 10 mM) up to 20 h post-irradiation while a level of radioprotection was found after 5 h exposure to higher doses up to 100 mM. By contrast, all doses of azide examined (5-50 mM) induced apoptotic radioprotection at all times examined. Glycolytic flux and ATP levels fell rapidly with increasing 2DG dose but energy charge remained unchanged. Glycolysis was less influenced by azide, with ATP levels being initially maintained after exposure but decreasing in a dose-dependent manner at 3 h post-irradiation. However, energy charge was unaffected by azide at the concentrations examined. CONCLUSIONS: Both 2DG and azide can influence radiation-induced apoptosis possibly through their effects on glycolysis and ATP levels. We suggest that modulation of energy metabolism provides mechanistic insight into radiation-induced apoptotic pathways.

LPA1 receptor-deficient mice have phenotypic changes observed in psychiatric disease.

Several psychiatric diseases, including schizophrenia, are thought to have a developmental aetiology, but to date no clear link has been made between psychiatric disease and a specific developmental process. LPA(1) is a G(i)-coupled seven transmembrane receptor with high affinity for lysophosphatidic acid. Although LPA(1) is expressed in several peripheral tissues, in the nervous system it shows relatively restricted temporal expression to neuroepithelia during CNS development and to myelinating glia in the adult. We report the detailed neurological and behavioural analysis of mice homozygous for a targeted deletion at the lpa(1) locus. Our observations reveal a marked deficit in prepulse inhibition, widespread changes in the levels and turnover of the neurotransmitter 5-HT, a brain region-specific alteration in levels of amino acids, and a craniofacial dysmorphism in these mice. We suggest that the loss of LPA(1) receptor generates defects resembling those found in psychiatric disease.

Does cardiologist- or radiographer-operated fluoroscopy and image acquisition influence optimization of patient radiation exposure during routine coronary angiography?

The operator of radiation exposure during coronary angiography varies between different centres. The purpose of this study was to explore whether radiation dose was lower during cardiologist- or radiographer-controlled radiation exposure and to determine if the grade of cardiologist performing angiography influenced radiation dose. Patients were randomly allocated either to cardiologist- or radiographer-controlled radiation exposure during coronary angiography. Screening time and radiation dose during fluoroscopy and image acquisition, measured by dose-area product meter, were recorded. Mean radiation dose during cardiologist-controlled radiation exposure (n=176) of 15.6 Gy cm(2) (95% confidence interval (CI), 14.4-16.8) was significantly lower than that produced by the radiographer-controlled group (n=192) of 17.3 Gy cm(2) (95% CI, 16.2-18.6) (p<0.044). There was no significant difference in screening times produced by the two groups of radiation exposure operators. The difference in radiation dose produced by the two operator groups was principally owing to exposure produced at image acquisition. Irrespective of radiation exposure operator, consultant cardiologists produced significantly lower screening times and radiation doses compared with registrars. During routine coronary angiography, radiographer-controlled radiation exposure does not reduce screening time or radiation dose. Senior cardiologists produce the lowest radiation doses during coronary angiography when they are responsible for radiation exposure.

Increased cortical expression of the orexin-1 receptor following permanent middle cerebral artery occlusion in the rat.

The orexins (hypocretins) have recently been implicated in neurodegeneration associated with narcolepsy. Therefore, the current study was designed to investigate changes in the expression of prepro-orexin and the orexin receptors, OX1R and OX2R following permanent middle cerebral artery occlusion (MCAO) in the rat. Six and twenty-four hours following MCAO, increased OX1R mRNA and protein expression (as assessed by Western blotting and immunohistochemistry) was detected in the ischaemic cortex compared with control tissue. In contrast, however, no increase in OX2R mRNA was detected at any time-point and prepro-orexin levels in the cortex were below assay detection levels. This study shows that orexin receptor localization is altered following cerebral ischaemia. The development of selective orexin receptor antagonists will be crucial in establishing a role for this family of novel peptides in the mechanisms underlying ischaemic cell death.

The behavioural effect of middle cerebral artery occlusion on apolipoprotein-E deficient mice.

The behavioural effects of middle cerebral artery occlusion (MCAO) in apolipoprotein-E deficient (Apo-E KO) mice were investigated using a modified SHIRPA protocol and compared with effects in wild type littermate controls. The MCA was permanently occluded by insertion of an intraluminal filament to its origin on the Circle of Willis and behavioural responses were observed 24 h later. MCAO treatment caused a range of changes in the wild type mice whereas, few differences were observed in the Apo-E KO mice in the behavioural observation. In the rotarod task, MCAO operated wild type mice showed a significant reduction in performance compared with sham-operated and non-operated animals. In contrast, both sham and MCAO operated Apo-E KO mice showed significant impairment compared with non-operated controls. A significant reduction in performance was also observed in sham-operated Apo-E KO compared with sham-operated wild type mice. In locomotor activity tests, no significant reduction in activity was observed between non-operated and sham-operated wild type controls, whereas a significant reduction was found between sham operated and MCAO operated mice. In the Apo-E KO mice, both sham and MCAO-operated animals showed a reduction in locomotor activity compared with non-operated mice. Furthermore, Apo-E KO MCAO mice showed a worsened deficit in locomotor activity, which was significantly correlated with exacerbated cortical lesion volume, unlike wild-type MCAO mice. This study shows that Apo-E KO animals demonstrate an impaired functional recovery post surgery which may be further compounded by post experimental stroke and also demonstrates the utility of the SHIRPA test system for investigating behavioural changes in functional outcome post stroke.

Thrombolytics in infectious endocarditis associated myocardial infarction.

The use of thrombolytics in the management of acute myocardial infarction in eligible patients is the accepted standard of practice. We present the case of an embolic myocardial infarction in the setting of acute infectious endocarditis, treated with thrombolytics, resulting in a massive intracerebral hemorrhage and the patient's death. Historical and current literature has shown a consistent and significant incidence of concurrent intracerebral mycotic aneurysms in the setting of infectious endocarditis. Despite this, a literature review of contraindications to the use of thrombolytics rarely recognizes endocarditis as a contraindication. It is imperative that the etiology for myocardial infarction be identified; if contraindications to thrombolytic treatment exist, alternative therapeutic interventions must be pursued. This case highlights the importance of the correct etiologic diagnosis of myocardial ischemia, and increases the awareness of the significant risks of intracerebral hemorrhage associated with the use of thrombolytics in the setting of endocarditis.

Up-regulation of secretoneurin immunoreactivity and secretogranin II mRNA in rat striatum following 6-hydroxydopamine lesioning and chronic L-DOPA treatment.

Destruction of the nigro-striatal pathway in Parkinson's disease and treatment with L-DOPA lead to persistent alterations in basal ganglia output pathways that are poorly characterised. Differential display mRNA analysis was used to study the effects of 6-hydroxydopamine-induced lesions of the medial forebrain bundle on gene expression in the rat striatum. One up-regulated cDNA identified in two independent groups of 6-hydroxydopamine-lesioned animals was cloned and sequence analysis showed 97% homology to secretogranin II. Differential up-regulation of secretogranin II following 6-hydroxydopamine lesioning was confirmed in a further group of 6-hydroxydopamine-lesioned rats using TaqMan real time quantitative reverse transcription-polymerase chain reaction. Following chronic L-DOPA treatment of 6-hydroxydopamine-lesioned rats, secretogranin II mRNA was further up-regulated to a similar degree to that observed for preproenkephalin A mRNA expression. Immunohistochemical analysis confirmed the increase in secretogranin II peptide levels in striatal neurones in 6-hydroxydopamine-lesioned rats following chronic L-DOPA treatment. The increase in secretogranin II mRNA occurring following destruction of the nigro-striatal pathway and chronic L-DOPA treatment may result in an increase in secretoneurin levels, which could be important for the regulation of striatal output pathways.

Increased responsiveness of dopamine to atypical, but not typical antipsychotics in the medial prefrontal cortex of rats reared in isolation.

Dopaminergic hypofunction in the medial prefrontal cortex (mPFC) has been associated with the aetiology of negative symptoms and cognitive dysfunction of schizophrenia, which are both alleviated by clozapine and other atypical antipsychotics such as olanzapine. In rodents, early life exposure to stressful experiences such as social isolation produces a spectrum of symptoms emerging in adult life, which can be restored by antipsychotic drugs. The present series of experiments sought to investigate the effect of clozapine (5-10 mg/kg s.c.), olanzapine (5 mg/kg s.c.), and haloperidol (0.5 mg/kg s.c.) on dopamine (DA) and amino acids in the prelimbic/infralimbic subregion of the mPFC in group- and isolation-reared rats. Rats reared in isolation showed significant and robust deficits in prepulse inhibition of the acoustic startle. In group-reared animals, both clozapine and olanzapine produced a significant increase in DA outflow in the mPFC. Isolation-reared rats showed a significant increase in responsiveness to both atypical antipsychotics compared with group-reared animals. In contrast, the administration of haloperidol failed to modify dialysate DA levels in mPFC in either group- or isolation-reared animals. The results also show a positive relationship between the potency of the tested antipsychotics to increase the release of DA in the mPFC and their respective affinities for 5-HT1A relative to DA D2 or D3 receptors. Finally, isolation-reared rats showed enhanced neurochemical responses to the highest dose of clozapine as indexed by alanine, aspartate, GABA, glutamine, glutamate, histidine, and tyrosine. The increased DA responsiveness to the atypical antipsychotic drugs clozapine and olanzapine may explain, at least in part, clozapine- and olanzapine-induced reversal of some of the major behavioral components of the social isolation syndrome, namely hyperactivity and attention deficit.

In vivo characterization of basal amino acid levels in subregions of the rat nucleus accumbens: effect of a dopamine D(3)/D(2) agonist.

Recent evidence demonstrates that two subdivisions of the nucleus accumbens, the dorsolateral core and the ventromedial shell can be distinguished by morphological, immunohistochemical and chemoarchitectural differences. In the present study, we measured basal levels of amino acids in microdialysates from both the shell and core subterritories of the nucleus accumbens in freely moving rats using HPLC with fluorescence detection. The effect of the dopamine D(3)/D(2) receptor agonist quinelorane (30 microg/kg s.c.) was then investigated in both subregions. With the exception of glutamate, histidine, and serine, which showed similar levels in both subterritories, alanine, arginine, aspartate, gamma-aminobutyric acid, glutamine, and tyrosine were significantly higher in the shell compared with the core. In contrast, taurine levels were significantly lower in the shell than in the core. A particularly striking difference across subregions of the nucleus accumbens was observed for basal GABA levels with a shell/core ratio of 18.5. Among all the amino acids investigated in the present study, quinelorane selectively decreased dialysate GABA levels in the core subregion of the nucleus accumbens. The results of the present study point to specific profiles of both shell and core in terms of: (1) basal chemical neuroanatomical markers for amino acids; and (2) GABAergic response to the DA D(3)/D(2) agonist quinelorane.

A cross-cultural comparison of resilience in adolescents.

The purpose of this study was to continue the process of clarifying the concept of resilience in adolescence. At the completion of the first phase of this clarification process in 1997, it became evident that adolescents believed resilience hurt them more than helped them and encompassed such dimensions as self-protection and survival. To gain the broadest understanding of the adolescent's perception of resilience, this study qualitatively explored those perceptions from adolescents in varied socioeconomic and cultural environments. Using a focus-group format, we queried 40 adolescents from New England and Ghana about their perceptions of adversity, overcoming adversities, and resilience. The results indicated that irrespective of age, gender, culture, and socioeconomic status, all the adolescents believed that they were resilient; however, overcoming adversities and being resilient were different depending on the presence or absence of consistent, loving, caring, mentoring adults who helped the adolescent traverse the adversities of life. Those adolescents who were without such support systems (found predominately in the New England sample) showed survival and self-protective forms of resilience, whereas those with such support systems (found predominately in the Ghanaian sample) showed a connected form of resilience. Further research is needed; however, adolescents have given clear messages in two studies indicating that being resilient can hurt them as much as it may help them. When fostering resilience, consideration should be given to what kind of resilience is being fostered.