A RCT of peer-mentoring for first-time mothers in socially disadvantaged areas (the moments study)

Objective: Interventions to reduce health inequalities for young children and their mothers are important: involving peers is recommended, but evidence of value for this approach is limited. The authors aimed to examine the effect of an innovative tailored peer-mentoring programme, based on perceived needs, for first-time mothers in socio-economically deprived communities. Design: Randomised controlled trial; parallel qualitative study with purposive samples using semistructured interviews. Setting: Socio-economically disadvantaged areas, Belfast. Participants: Primigravidae, aged 16-30 years, without significant co-morbidity. Intervention: Peer-mentoring by a lay-worker fortnightly during pregnancy and monthly for the following year, tailored to participants' wishes (home visits/telephone contacts), additional to usual care. Main outcome measures: Infant psychomotor and mental development (Bayley Scales of Infant Development (BSID-II)) at 1 year, assessed by an observer blinded to group allocation. Mothers' health at 1 year postnatal (SF-36). Results: Of 534 women invited, 343(64%) participated; 85%, with their children, completed outcome assessments (140 of 172 intervention; 152 of 171 controls). Intervention and control groups did not differ in BSID-II psychomotor (mean difference 1.64, 95% CI -0.94 to 4.21) or mental (-0.81, -2.78 to 1.16) scores, nor SF-36 physical functioning (-5.4, -11.6 to 0.7) or mental health (-1.8, -6.1 to 2.6). Women valued advice given in context of personal experience of child-rearing. Mentors gained health-related knowledge, personal skills and new employment opportunities. Conclusions: Despite possible longer-term social advantage, this peer-mentoring programme showed no benefit for infant development or maternal health at 1 year. Further rigorous evaluation of important outcomes of complex interventions promoting health for children in socially disadvantaged communities is warranted. Trial registration no: ISRCTN 55055030.

Combining and integrating life /social sciences and citizen trainers in Nurse Education - a N. Ireland initiative

Before commencement of the academic year 2012/2013 the social sciences, public health and the biomedical sciences were taught to separate modules. This reinforced the idea off separate disciplines certainly for some of the younger students and a failure to appreciate the interconnectedness (whole person) perspective on health; separately modules taught and assessed in separate silos. There was limited understanding by the lecturers of the other areas that they were not teaching to -reflecting perhaps a dis-coordinated approach to health sciences (Mason and Whitehead 2003). As a result of significant discussion and interdisciplinary negotiation the life, social sciences public health/ health education were drawn together in the one module for the academic year 2012/13. The module provides the undergraduate students with an introduction to an understanding of Life Sciences, psychology, sociology and public health and their contribution within the context of nursing and midwifery. Each week’s teaching seeks to reflect against the other module delivered in first year - addressing clinical skills. The teaching is developing innovative e-learning approaches, including the use of a virtual community. The intention is to provide the student with a more integrated understanding and teaching to the individual’s health and to health within a social context (Lin 2001; Iles- Shih 2011). The focus is on health promotion rather than disease management. The module runs in three phases across the student’s first-year and teachers to the field of adult mental health, learning disability, children’s nursing and the midwifery students -progressively building on the student’s clinical experience. The predominant focus of the module remains on health and reflecting aspects of life and social life within N. Ireland. One of the particular areas of interest and an area of particular sensitivity is engaging the students to the context of the Northern Ireland civil unrest (the Troubles); this involves a co-educational initiative with service users, only previously attempted with social work students (Duffy 2012). The service users are represented by WAVE an organisation offering care and support to bereaved, traumatised or injured as a result of the violent civil conflict `the Troubles’. The `Troubles’ had ranged over an extended period and apart from the more evident and visual impact of death and injury, the community is marked by a disproportionate level of civil unrest, the extremes of bereavement, imprisonment, displacement antisocial behaviour and family dysfunction (Coulter et al. 2012). As co-educators with the School of Nursing and Midwifery, WAVE deliver a core lecture (augmented by online material), then followed by tutorials. The tutorials are substantially led by those who had been involved with and experienced loss and trauma as a result of the conflict (Health Service users) as `citizen trainers’ and provide an opportunity for them to share their experience and their recollection of personal interaction with nursing and midwifery students; in improving their understanding of the impact of `The Troubles’ on patients and clients affected by the events (Coulter et al. 2012) and to help better provide a quality of care cognisant of the particular needs of those affected by `the Troubles’ in N.Ireland. This approach is relatively unique to nursing in N. Ireland in that it involves many of those directly involved with and injured by the `Troubles’ as `citizen trainers’ and clearly reflects the School’s policy of progressively engaging with users and carers of nursing and midwifery services as co-educators to students (Repper & Breeze 2006). Only now could perhaps such a sensitive level of training to student nurses and midwives be delivered across communities with potential educative lessons for other communities experiencing significant civil unrest and sectarian conflict.

Visualization of the earliest steps of gammadelta T cell development in the adult thymus.

The checkpoint in cell development that controls successful T cell receptor (TCR) gene rearrangements remains poorly characterized. Using mice expressing a reporter gene 'knocked into' the Tcrd constant region gene, we have characterized many of the events that mark the life of early cells in the adult thymus. We identify the developmental stage during which the Tcrd locus 'opens' in early T cell progenitors and show that a single checkpoint controls cell development during the penultimate CD4-CD8- stage. Passage through this checkpoint required the assembly of TCR heterodimers on the cell surface and signaling via the Lat adaptor protein. In addition, we show that selection triggered a phase of sustained proliferation similar to that induced by the pre-TCR.

Development of selective media for the isolation of yeasts and filamentous fungi from the sputum of adult patients with cystic fibrosis (CF)

Yeasts and filamentous fungi are beginning to emerge as significant microbial pathogens in patients with cystic fibrosis (CF), particularly in relation to allergic-type responses, as seen in patients with allergic bronchopulmonary aspergillosis (ABPA), Aspergillus bronchitis and in invasive fungal disease in lung transplant patients. Four fungal media were compared in this study, including Sabouraud Dextrose Agar (SDA) and Medium B, with and without the addition of selective antibiotics, where antibiotic-supplemented media were designated with (+). These media were compared for their ability to suppress contaminating, mainly Gram-ve pathogens, in CF sputa (Pseudomonas aeruginosa, Burkholderia cepacia complex [BCC] organisms) and to enhance the growth of fungi present in CF sputum. Medium B consisted of glucose (16.7 g/l), agar (20 g/l), yeast extract (30 g/l) and peptone (6.8 g/l) at pH 6.3 and both SDA(+) and Medium B+ were supplemented with cotrimethoxazole, 128 mg/l; chloramphenicol, 50 mg/l; ceftazidime, 32 mg/l; colistin, 24 mg/l). Employment of SDA(+) or Medium B+ allowed an increase in specificity in the detection of yeasts and moulds, by 42.8% and 39.3%, respectively, over SDA when used solely. SDA(+) had a greater ability than Medium B+ to suppress bacterial growth from predominantly Gram-ve co-colonisers. This is a significant benefit when attempting to detect and isolate fungi from the sputum of CF patients, as it largely suppressed any bacterial growth, with the exception of the BCC organisms, thus allowing for an increased opportunity to detect target fungal organisms in sputum and represented a significant improvement over the commercial medium (SDA), which is currently used. Overall, both novel selective media were superior in their ability to suppress bacteria in comparison with the commercially available SDA medium, which is routinely employed in most clinical microbiology diagnostic laboratories presently. Alternatively, Medium B+ had a great ability to grow fungi than SDA(+) and when employed together, the specificity of combined use was 82%, with a sensitivity for yeasts, filamentous fungi, and combined overall fungi of 96.0%, 92.3% and 96.0%, respectively. Overall, when employing one fungal selective medium for the routine detection of yeasts and filamentous fungi in the sputum of CF patients, we would recommend employment of Medium B+. However, we would recommend the combined employment of SDA(+) and Medium B+, in order to synergistically isolate and detect the greatest number of fungi present in CF sputa. (C) 2008 European Cystic Fibrosis Society. Published by Elsevier B.V All rights reserved.

Development of a novel PCR assay for the identification of the black yeast, Exophiala (Wangiella) dermatitidis from adult patients with cystic fibrosis (CF)

Cystic fibrosis (CF) patients may suffer increased morbidity and mortality through colonisation, allergy and invasive infection from fungi. The black yeast, Exophiala dermatitidis (synonym Wangiella dermatitidis) has been found with increasing frequency in sputum specimens of CF patients, with reported isolation rates ranging from 1.1 to 15.7%. At present, no diagnostic PCR exists to aid with the clinical laboratory detection and identification of this organism. A novel species-specific PCR-based assay was developed for the detection of E. dermatitidis, based on employment of rDNA operons and interspacer (ITS) regions between these rDNA operons. Two novel primers, (designated ExdF & ExdR) were designed in silico with the aid of computer-aided alignment software and with the alignment of multiple species of Exophiala, as well as with other commonly described yeasts and filamentous fungi within CF sputum, including Candida. Aspergillus and Scedosporium. An amplicon of approximately 455 by was generated, spanning the partial ITS I region - the complete 5.8S rDNA region - partial ITS2 region, employing ExdF (forward primer [16-mer], 5'-CCG CCT ATT CAG GTC C-3' and ExdR (reverse primer [16-mer], 5'-TCT CTC CCA CTC CCG C-3', was employed and optimised on extracted genomic DNA from a well characterised culture of E. dermatitidis, as well as with high quality genomic DNA template from a further 16 unrelated fungi, including Candida albicans, C. dubliniensis, C. parapsilosis, C. glabrata, Scedosporium apiospermum, Penicillium sp., Aspergillus fumigatus, Aspergillus versicolor, Pichia guilliermondii, Rhodotorula sp., Trichosporon sp., Aureobasidium pullulans, Fusarium sp., Mucor hiemalis, Bionectria ochroleuca, Gibberella pulicaris. Results demonstrated that only DNA from E. dermatitidis gave an amplification product of the expected sire, whilst none of the other fungi were amplifiable. Subsequent employment of this primer pair detected this yeast from mycological cultures from 2/50 (4%) adult CF patients. These two patients were the only patients who were previously shown to have a cultural history of E. dermatitidis from their sputum. E. dermatitidis is a slow-growing fungus, which usually takes up to two weeks to culture in the microbiology laboratory and therefore is slow to detect conventionally, with the risk of bacterial overgrowth from common co-habiting pan- and multiresistant bacterial pathogens from sputum. namely Pseudomonas aeruginosa and Burkholderia cepacia complex organisms, hence this species-specific PCR assay may help detect this organism from CF sputum more specifically and rapidly. Overall, employment of this novel assay nay help in the understanding of the occurrence. aetiology and epidemiology of E. dermatitidis, as an emerging fungal agent in patients with CF. (C) 2008 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Age related differences in mental health scale scores and depression diagnosis: Adult responses to the CIDI-SF and MHI-5.

Inconsistencies surrounding the prevalence levels of depression in later life suggest that the measurement of depression in older people may be problematic. The current study aimed to map responses to a depressive symptom scale, the Mental Health Index-5 (MHI-5) which is part of the Short form 36 (SF-36, Ware et al., 1993) against the diagnostic screening items of the Composite International Diagnostic Instrument-Short Form (CIDI-SF, Kessler et al., 1998) to examine disagreement rates across age groups. The study examined data from a national random sample of 10,641 participants living in Ireland, 58.8% were female and 19% were over 65 (SLÁN, 2007). CIDI-SF depression screening endorsement was lower in older groups, whereas mean MHI-5 depressive symptoms showed less change across age groups. Results showed that the odds of MHI-5 endorsers aged 18–44 endorsing CIDI-SF screening questions were 5 times and 4.5 times (dysphoria and anhedonia, respectively) greater than the odds of people aged 75 or more endorsing these items. Findings suggest that although the risk of depressive disorder may decrease with age, complex diagnostic screening questions may exaggerate lower rates of depression among older people.

RNA interference in adult Ascaris suum - an opportunity for the development of a functional genomics platform that supports organism-, tissue- and cell-based biology in a nematode parasite

The sustainable control of animal parasitic nematodes requires the development of efficient functional genomics platforms to facilitate target validation and enhance anthelmintic discovery. Unfortunately, the utility of RNA interference (RNAi) for the validation of novel drug targets in nematode parasites remains problematic. Ascaris suum is an important veterinary parasite and a zoonotic pathogen. Here we show that adult A. suum is RNAi competent, and highlight the induction, spread and consistency of RNAi across multiple tissue types. This platform provides a new opportunity to undertake whole organism-, tissue- and cell-level gene function studies to enhance target validation processes for nematode parasites of veterinary/medical significance.

Suppression of the Insulin Receptors in Adult Schistosoma japonicum Impacts on Parasite Growth and Development: Further Evidence of Vaccine Potential

To further investigate the importance of insulin signaling in the growth, development, sexual maturation and egg production of adult schistosomes, we have focused attention on the insulin receptors (SjIRs) of Schistosoma japonicum, which we have previously cloned and partially characterised. We now show, by Biolayer Interferometry, that human insulin can bind the L1 subdomain (insulin binding domain) of recombinant (r)SjIR1 and rSjIR2 (designated SjLD1 and SjLD2) produced using the Drosophila S2 protein expression system. We have then used RNA interference (RNAi) to knock down the expression of the SjIRs in adult S. japonicum in vitro and show that, in addition to their reduced transcription, the transcript levels of other important downstream genes within the insulin pathway, associated with glucose metabolism and schistosome fecundity, were also impacted substantially. Further, a significant decrease in glucose uptake was observed in the SjIR-knockdown worms compared with luciferase controls. In vaccine/challenge experiments, we found that rSjLD1 and rSjLD2 depressed female growth, intestinal granuloma density and faecal egg production in S. japonicum in mice presented with a low dose challenge infection. These data re-emphasize the potential of the SjIRs as veterinary transmission blocking vaccine candidates against zoonotic schistosomiasis japonica in China and the Philippines.

The effects of blood pressure lowering on development of cognitive impairment and dementia in patients without apparent prior cerebrovascular disease

BACKGROUND: Hypertension and cognitive impairment are prevalent in older people. It is known that hypertension is a direct risk factor for vascular dementia and recent studies have suggested hypertension also impacts upon prevalence of Alzheimer's disease. The question is therefore whether treatment of hypertension lowers the rate of cognitive decline. OBJECTIVES: To assess the effects of blood pressure lowering treatments for the prevention of dementia and cognitive decline in patients with hypertension but no history of cerebrovascular disease. SEARCH STRATEGY: The trials were identified through a search of CDCIG's Specialised Register, CENTRAL, MEDLINE, EMBASE, PsycINFO and CINAHL on 27 April 2005. SELECTION CRITERIA: Randomized, double-blind, placebo controlled trials in which pharmacological or non-pharmacological interventions to lower blood pressure were given for at least six months. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed trial quality and extracted data. The following outcomes were assessed: incidence of dementia, cognitive change from baseline, blood pressure level, incidence and severity of side effects and quality of life. MAIN RESULTS: Three trials including 12,091 hypertensive subjects were identified. Average age was 72.8 years. Participants were recruited from industrialised countries. Mean blood pressure at entry across the studies was 170/84 mmHg. All trials instituted a stepped care approach to hypertension treatment, starting with a calcium-channel blocker, a diuretic or an angiotensin receptor blocker. The combined result of the three trials reporting incidence of dementia indicated no significant difference between treatment and placebo (Odds Ratio (OR) = 0.89, 95% CI 0.69, 1.16). Blood pressure reduction resulted in a 11% relative risk reduction of dementia in patients with no prior cerebrovascular disease but this effect was not statistically significant (p = 0.38) and there was considerable heterogeneity between the trials. The combined results from the two trials reporting change in Mini Mental State Examination (MMSE) did not indicate a benefit from treatment (Weighted Mean Difference (WMD) = 0.10, 95% CI -0.03, 0.23). Both systolic and diastolic blood pressure levels were reduced significantly in the two trials assessing this outcome (WMD = -7.53, 95% CI -8.28, -6.77 for systolic blood pressure, WMD = -3.87, 95% CI -4.25, -3.50 for diastolic blood pressure).Two trials reported adverse effects requiring discontinuation of treatment and the combined results indicated a significant benefit from placebo (OR = 1.18, 95% CI 1.06, 1.30). When analysed separately, however, more patients on placebo in SCOPE were likely to discontinue treatment due to side effects; the converse was true in SHEP 1991. Quality of life data could not be analysed in the three studies. There was difficulty with the control group in this review as many of the control subjects received antihypertensive treatment because their blood pressures exceeded pre-set values. In most cases the study became a comparison between the study drug against a usual antihypertensive regimen. AUTHORS' CONCLUSIONS: There was no convincing evidence from the trials identified that blood pressure lowering prevents the development of dementia or cognitive impairment in hypertensive patients with no apparent prior cerebrovascular disease. There were significant problems identified with analysing the data, however, due to the number of patients lost to follow-up and the number of placebo patients given active treatment. This introduced bias. More robust results may be obtained by analysing one year data to reduce differential drop-out or by conducting a meta-analysis using individual patient data.