Effect of increasing dietary folate on red-cell folate: Implications for prevention of neural tube defects

Background Recommendations by the UK Department of Health suggest that protection from neural tube defects (NTD) can be achieved through intakes of an extra 400 mu g daily of folate/folic acid as natural food, foods fortified with folic acid, or supplements. The assumption is that all three routes of intervention would have equal effects on folate status.

Methods We assessed the effectiveness of these suggested routes of intervention in optimising folate status. 62 women were recruited from the University staff and students to take part in a 3-month intervention study. Participants were randomly assigned to one of the following five groups: folic acid supplement (400 mu g/day; I); folic-acid-fortified foods (an additional 400 mu g/day; II); dietary folate (an additional 400 mu g/day; III); dietary advice (IV), and control (V). Responses to intervention were assessed as changes in red-cell folate between preintervention and postintervention values.

Findings 41 women completed the intervention study. Red-cell folate concentrations increased significantly over the 3 months in the groups taking folic acid supplements (group I) or food fortified with folic acid (group II) only (p<0.01 for both groups). By contrast, although aggressive intervention with dietary folate (group III) or dietary advice (group IV) significantly increased intake of food folate (p<0.001 and p<0.05, respectively), there was no significant change in folate status.

Interpretation We have shown that compared with supplements and fortified food, consumption of extra folate as natural food folate is relatively ineffective at increasing folate status. We believe that advice to women to consume folate-rich foods as a means to optimise folate status is misleading.

Mutagenesis of RpoE-like sigma factor genes in Bdellovibrio reveals differential control of groEL and two groES genes

BACKGROUND: Bdellovibrio bacteriovorus HD100 must regulate genes in response to a variety of environmental conditions as it enters, preys upon and leaves other bacteria, or grows axenically without prey. In addition to "housekeeping" sigma factors, its genome encodes several alternate sigma factors, including 2 Group IV-RpoE-like proteins, which may be involved in the complex regulation of its predatory lifestyle.

RESULTS: We find that one sigma factor gene, bd3314, cannot be deleted from Bdellovibrio in either predatory or prey-independent growth states, and is therefore possibly essential, likely being an alternate sigma 70. Deletion of one of two Group IV-like sigma factor genes, bd0881, affects flagellar gene regulation and results in less efficient predation, although not due to motility changes; deletion of the second, bd0743, showed that it normally represses chaperone gene expression and intriguingly we find an alternative groES gene is expressed at timepoints in the predatory cycle where intensive protein synthesis at Bdellovibrio septation, prior to prey lysis, will be occurring.

CONCLUSIONS: We have taken the first step in understanding how alternate sigma factors regulate different processes in the predatory lifecycle of Bdellovibrio and discovered that alternate chaperones regulated by one of them are expressed at different stages of the lifecycle.

Liquid coordination complexes: a new class of Lewis acids as safer alternatives to BF3 in synthesis of polyalphaolefins

Liquid coordination complexes (LCCs) are a new class of liquid Lewis acids, prepared by combining an excess of a metal halide (e.g. GaCl3) with a basic donor molecule (e.g. amides, amines or phosphines). LCCs were used to catalyse oligomerisation of 1-decene to polyalphaolefins (PAOs). Molecular weight distribution and physical properties of the produced oils were compliant with those required for low viscosity synthetic (Group IV) lubricant base oils. Kinematic viscosities at 100 °C of ca. 4 or 6 cSt were obtained, along with viscosity indexes above 120 and pour points below −57 °C. In industry, to achieve similar properties, BF3 gas is used as a catalyst. LCCs are proposed as a safer and economically attractive alternative to BF3 gas for the production of polyalphaolefins.

Lead: Inorganic Chemistry

The article covers basic inorganic chemistry of lead. As an introduction, the properties and historical uses of metallic lead are discussed, followed by aspects of lead toxicity, including the toxicity origins and effects of lead poisoning. Properties of lead as a heavy p-block element are discussed, with emphasis on the modern view of the so-called “inert pair effect”, including its origin, the influence on stability of lead oxidation states, and on the coordination chemistry of lead(II), viz., “sterically active lone pair”. This is followed by an overview of lead inorganic compounds, including halides, pseudohalides, oxides and chalcogenides, hydroxides and their chalcogenide analogs, alkoxides, oxoacids, O-donors, S- and Se-donors, Group 15 donors, compounds with lead-transition metal bonds, and finally metallic clusters (Zintl phases). This is by no means a comprehensive review, rather compounds representative for each class were presented. In most sections, structural aspects of each class of compounds are discussed, followed by applications, with the focus on modern uses in material science.

Synthesis, Kinetic Evaluation and Utilization of a Biotinylated Dipeptide Proline Diphenyl Phosphonate for the Disclosure of Dipeptidyl Peptidase IV-like Serine Proteases

In this study, we report on the synthesis, kinetic characterisation, and application of a novel biotinylated and active site-directed inactivator of dipeptidyl peptidase IV (DPP-IV). Thus, the dipeptide-derived proline diphenyl phosphonate NH(2)-Glu(biotinyl-PEG)-Pro(P)(OPh)(2) has been prepared by a combination of classical solution- and solid-phase methodologies and has been shown to be an irreversible inhibitor of porcine DPP-IV, exhibiting an over all second-order rate constant (k(i)/K(i)) for inhibition of 1.57 x 10(3) M(-1) min(-1). This value compares favourably with previously reported rates of inactivation of DPP-IV by dipeptides containing a P(1) proline diphenyl phosphonate grouping [B. Boduszek, J. Oleksyszyn, C.M. Kam, J. Selzler, R.E. Smith, J.C. Powers, Dipeptide phophonates as inhibitors of dipeptidyl peptidase IV, J. Med. Chem. 37 (1994) 3969-3976; B.F. Gilmore, J.F. Lynas, C.J. Scott, C. McGoohan, L. Martin, B. Walker, Dipeptide proline diphenyl phosphonates are potent, irreversible inhibitors of seprase (FAPalpha), Biochem, Biophys. Res. Commun. 346 (2006) 436-446.], thus demonstrating that the incorporation of the side-chain modified (N-biotinyl-3-(2-(2-(3-aminopropyloxy)-ethoxy)-ethoxy)-propyl) glutamic acid residue at the P(2) position is compatible with inhibitor efficacy. The utilisation of this probe for the detection of both purified dipeptidyl peptidase IV and the disclosure of a dipeptidyl peptidase IV-like activity from a clinical isolate of Porphyromonas gingivalis, using established electrophoretic and Western blotting techniques previously developed by our group, is also demonstrated.

Precision Teaching in IV Fluid Prescribing and Patient Safety

OBJECTIVES: Precision Teaching (PT) has been shown to be an effective intervention to assess teaching method effectiveness and evaluate learning outcomes. SAFMEDS (Say All Fast Minute Every Day Shuffled) are a practice/assessment procedure within the PT framework to assist learning and fluency. We explored the effects of a brief intervention with PT, to impart high frequency performance in safe intravenous fluid prescription in a group of final year undergraduate medical students.
METHODS: 133 final year undergraduate medical students completed a multiple choice question (MCQ) test on safe IV fluid prescription at the beginning and end of the study. The control group (n= 76) of students were taught using a current standardized teaching method. Students allocated to the intervention arm of the study were additionally instructed on PT and the use of SAFMEDS. The study group (n = 57) received 50 SAFMEDS cards containing information on the principles of IV fluid prescription scenarios. These students were trained/tested twice per day for 1 minute.
RESULTS: Interim analysis showed that the study group displayed an improvement in fluency and accuracy as the study progressed. There was a statistically significant improvement in MCQ performance for the PT group compared with the control group between the beginning and end of the study (35% vs 15%).
CONCLUSION: These results suggest PT employing SAFMEDS is an effective method for improving fluency, accuracy and patient safety in intravenous fluid prescribing amongst undergraduate medical students.

Favorable effect on acute and chronic graft-versus-host disease with cyclophosphamide and in vivo anti-CD52 monoclonal antibodies for marrow transplantation from HLA-identical sibling donors for acquired aplastic anemia

Between August 1989 and November 2003, 33 patients at our center with acquired aplastic anemia underwent bone marrow transplantation (BMT) from HLA-identical sibling donors with cyclophosphamide and in vivo anti-CD52 monoclonal antibodies (MoAb) for conditioning. The median age at BMT was 17 years (range, 4-46 years). Before BMT, 58% were heavily transfused (>50 transfusions), and 42% had previously experienced treatment failure with antithymocyte globulin-based immunosuppressive therapy. Unmanipulated bone marrow was used as the source of stem cells in all patients except 1. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine alone in 19 (58%) patients; 14 received anti-CD52 MoAb in addition to cyclosporine. The conditioning regimen was well tolerated without significant acute toxicity. Graft failure was seen in 8 patients (primary, n = 4; secondary, n = 4). Of those whose grafts failed, 4 survived long-term (complete autologous recovery, n = 2; rescue with previously stored marrow, n = 1; second allograft, n = 1). The cumulative incidence of graft failure and grade II to IV acute and chronic GVHD was 24%, 14%, and 4%, respectively. None developed extensive chronic GVHD. With a median follow-up of 59 months, the 5-year survival was 81% (95% confidence interval, 68%-96%). No unexpected early or late infectious or noninfectious complications were observed. We conclude that the conditioning regimen containing cyclophosphamide and anti-CD52 MoAb is well tolerated and effective for acquired aplastic anemia with HLA-matched sibling donors. The favorable effect on the incidence and severity of GVHD is noteworthy in this study and warrants further investigation.

Campath-1G in vivo confers a low incidence of graft-versus-host disease associated with a high incidence of mixed chimaerism after bone marrow transplantation for severe aplastic anaemia using HLA-identical sibling donors

We have evaluated the effect of in vivo Campath-1G on engraftment and GVHD in 23 patients with severe aplastic anaemia transplanted from HLA-identical sibling donors. In 14 patients Campath 1g was given pre-transplant for up to 9 days in an attempt to overcome graft rejection (group 1). In nine patients Campath-1G was given pre-transplant, but also continued post-transplant until day +5 to reduce GVHD (group 2). There were three patients with late graft failure in group I following initial neutrophil engraftment, and four cases of grade II+ GVHD. In group II, two patients had early graft failure (no take), and there were no cases of acute GVHD out of seven evaluable patients. One patient in group I developed chronic GVHD of the liver, and two patients (one in each group) had transient localised chronic GVHD. PCR of short tandem repeats was used to evaluate chimaeric status in 13 patients. Of 11 patients with initial neutrophil engraftment, only one had 100% donor haemopoiesis at all times. The remaining patients had either transient mixed chimaerism or persistence of recipient (< 20%) cells. We conclude that in vivo Campath-1G is associated with a high incidence of mixed chimaerism which tips the balance away from GVHD but towards graft rejection.

Nurturing attachments in looked after children: a feasibility study of a group-based programme for carers

Introduction: The attachment related difficulties of Looked after Children are well recognised in literature with difficulties linked to early experiences hypothesised to be perpetuated by experiences of the care system itself. Recent policy guidelines have emphasised the importance of relationships for children in care, one of the most important being with their primary carer. Golding (2014) published a group format training resource entitled ‘Nurturing Attachments’ which aims to promote ‘therapeutic parenting’; however there is limited knowledge on the feasibility of this intensive approach.
Aims: To assess the feasibility of Nurturing Attachments through exploring (i.) recruitment, retention and attrition, (ii.) initial outcomes, (iii.) acceptability and (iv.) ability of the programme to be delivered in line with the manual content and structure.
Method Two Health and Social Care Trusts in NI participated in the study by facilitating a Nurturing Attachments group in each site with adoptive parents, foster carers and kinship carers (N = 26). Carers completed pre and post measures to explore initial outcome, completing an evaluation questionnaire to explore acceptability. Acceptability was also explored with Trust stakeholders and group facilitators through focus group and interview. To explore if the manual can be delivered as intended, each group completed debrief tools.
Results: The overall response rate for uptake was 13.9%, which impacted on engagement for a ‘treatment as usual’ group. Once engaged in the programme, attrition was low and attendance was high. Initial outcomes have shown positive effects for both young person and carers. Feedback suggests a positive response regarding acceptability with limited expressed concern. The manual can be delivered in a standardised way; however can be flexible enough to allow for group processes.
Conclusions: Further research is needed to continue to explore efficacy, however the current study has provided supporting evidence that Nurturing Attachments as an intervention has positively impacted on many levels of the LAAC system.