Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of ascaris reveals a novel fold and two discrete lipid-binding sites

Parasitic nematode worms cause serious health problems in humans and other animals. They can induce allergic-type immune responses, which can be harmful but may at the same time protect against the infections. Allergens are proteins that trigger allergic reactions and these parasites produce a type that is confined to nematodes, the nematode polyprotein allergens (NPAs). These are synthesized as large precursor proteins comprising repeating units of similar amino acid sequence that are subsequently cleaved into multiple copies of the allergen protein. NPAs bind small lipids such as fatty acids and retinol (Vitamin A) and probably transport these sensitive and insoluble compounds between the tissues of the worms. Nematodes cannot synthesize these lipids, so NPAs may also be crucial for extracting nutrients from their hosts. They may also be involved in altering immune responses by controlling the lipids by which the immune and inflammatory cells communicate. We describe the molecular structure of one unit of an NPA, the well-known ABA-1 allergen of Ascaris and find its structure to be of a type not previously found for lipid-binding proteins, and we describe the unusual sites where lipids bind within this structur

Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants.

ObjectiveTo analyze reasons for low enrollment in a randomized controlled trial (RCT) of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late preterm newborns.Study designThe original study was a multicenter RCT. Eligibility: ⩾34 weeks' gestation, <72 h old, mechanically ventilated, receiving inotrope. Primary outcome was NDI at 2 years; infants with diagnoses at high risk for NDI were excluded. This paper presents an analysis of reasons for low patient enrollment.ResultsTwo hundred and fifty-seven of the 932 otherwise eligible infants received inotropes; however, 207 (81%) had exclusionary diagnoses. Only 12 infants were randomized over 10 months; therefore, the study was terminated. Contributing factors included few eligible infants after exclusions, open-label steroid therapy and a narrow enrollment window.ConclusionDespite an observational study to estimate the population, very few infants were enrolled. Successful RCTs of emergent therapy may require fewer exclusions, a short-term primary outcome, waiver of consent and/or other alternatives

Effectiveness of moving on: an Australian designed generic self-management program for people with a chronic illness

Background: This paper presents the evaluation of “Moving On”, a generic self-management program for people with a chronic illness developed by Arthritis NSW. The program aims to help participants identify their need for behavior change and acquire the knowledge and skills to implement changes that promote their health and quality of life. Method: A prospective pragmatic randomised controlled trial involving two group programs in community settings: the intervention program (Moving On) and a control program (light physical activity). Participants were recruited by primary health care providers across the north-west region of metropolitan Sydney, Australia between June 2009 and October 2010. Patient outcomes were self-reported via pre- and post-program surveys completed at the time of enrolment and sixteen weeks after program commencement. Primary outcomes were change in self-efficacy (Self-efficacy for Managing Chronic Disease 6-Item Scale), self-management knowledge and behaviour and perceived health status (Self-Rated Health Scale and the Health Distress Scale). Results: A total of 388 patient referrals were received, of whom 250 (64.4%) enrolled in the study. Three patients withdrew prior to allocation. 25 block randomisations were performed by a statistician external to the research team: 123 patients were allocated to the intervention program and 124 were allocated to the control program. 97 (78.9%) of the intervention participants commenced their program. The overall attrition rate of 40.5% included withdrawals from the study and both programs. 24.4% of participants withdrew from the intervention program but not the study and 22.6% withdrew from the control program but not the study. A total of 62 patients completed the intervention program and follow-up evaluation survey and 77 patients completed the control program and follow- up evaluation survey. At 16 weeks follow-up there was no significant difference between intervention and control groups in self-efficacy; however, there was an increase in self-efficacy from baseline to follow-up for the intervention participants (t=−1.948, p=0.028). There were no significant differences in self-rated health or health distress scores between groups at follow-up, with both groups reporting a significant decrease in health distress scores. There was no significant difference between or within groups in self-management knowledge and stage of change of behaviours at follow-up. Intervention group attenders had significantly higher physical activity (t=−4.053, p=0.000) and nutrition scores (t=2.315, p= 0.01) at follow-up; however, these did not remain significant after adjustment for covariates. At follow-up, significantly more participants in the control group (20.8%) indicated that they did not have a self-management plan compared to those in the intervention group (8.8%) (X2=4.671, p=0.031). There were no significant changes in other self-management knowledge areas and behaviours after adjusting for covariates at follow-up. Conclusions: The study produced mixed findings. Differences between groups as allocated were diluted by the high proportion of patients not completing the program. Further monitoring and evaluation are needed of the impact and cost effectiveness of the program. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN1260900029821

Prognostic value of nuclear morphometry in patients with TNM stage T1 ovarian clear cell adenocarcinoma

In 40 patients with TNM stage T1 ovarian clear cell adenocarcinoma, we used nuclear morphometry to study the relations among morphometric variables, clinical prognostic factors and outcome. The presence of one or more giant nuclear cells was positively associated with death (OR = 10.6, P = 0.02) and tended to be associated with disease recurrence (OR = 5.1, P = 0.07). Nuclear irregularity (expressed in terms of the nuclear roundness factor) was positively associated with both death (OR = 8.6, P = 0.02) and disease recurrence (OR = 8.2, P = 0.02). A combination of giant nuclear cell presence or nuclear irregularity proved to be a useful prognostic indicator, with a sensitivity and specificity of 83% and 71% in the prediction of death, and 75% and 71% in the prediction of disease recurrence. Patients' age and substage were of no prognostic value. We conclude that the nuclear morphometric characteristics, especially the presence of giant nuclear cells and nuclear irregularity, may be useful in predicting outcome in patients with early stage ovarian clear cell adenocarcinoma. © 1999 Cancer Research Campaig

Transition of plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio

Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism

No straight lines – young women’s perceptions of their mental health and wellbeing during and after pregnancy: a systematic review and meta-ethnography

Background: Young mothers face mental health challenges during and after pregnancy including increased rates of depression compared to older mothers. While the prevention of teenage pregnancy in countries such as the United States and the United Kingdom has been a focus for policy and research in recent decades, the need to understand young women’s own experiences has been highlighted. The aim of this meta-ethnography was to examine young women’s perceptions of their mental health and wellbeing during and after pregnancy to provide new understandings of those experiences. Methods: A systematic review and meta-ethnographic synthesis of qualitative research was conducted. Seven databases were systematically searched and forward and backward searching conducted. Papers were included if they were from Organisation for Economic Co-operation and Development countries and explored mental health and wellbeing experiences of young mothers (age under 20 in pregnancy; under 25 at time of research) as a primary research question – or where evidence about mental health and wellbeing from participants was foregrounded. Nineteen papers were identified and the Critical Appraisal Skills Programme checklist for qualitative research used to appraise the evidence. Following the seven-step process of meta-ethnography, key constructs were examined within each study and then translated into one another. Results: Seven translated themes were identified forming a new line of argument wherein mental health and wellbeing was analysed as relating to individual bodily experiences; tied into past and present relationships; underpinned by economic insecurity and entangled with feelings of societal surveillance. There were ‘no straight lines’ in young women’s experiences, which were more complex than dominant narratives around overcoming adversity suggest. Conclusions: The synthesis concludes that health and social care professionals need to reflect on the operation of power and stigma in young women’s lives and its impact on wellbeing. It adds to understanding of young women’s mental health and wellbeing during and after pregnancy as located in physical and structural factors rather than individual capacities alone

Partial joint processing with efficient backhauling using particle swarm optimization

In cellular communication systems with frequency reuse factor of one, user terminals (UT) at the cell-edge are prone to intercell interference. Joint processing is one of the coordinated multipoint transmission techniques proposed to mitigate this interference. In the case of centralized joint processing, the channel state information fed back by the users need to be available at the central coordination node for precoding. The precoding weights (with the user data) need to be available at the corresponding base stations to serve the UTs. These increase the backhaul traffic. In this article, partial joint processing (PJP) is considered as a general framework that allows reducing the amount of required feedback. However, it is difficult to achieve a corresponding reduction on the backhaul related to the precoding weights, when a linear zero forcing beamforming technique is used. In this work, particle swarm optimization is proposed as a tool to design the precoding weights under feedback and backhaul constraints related to PJP. The precoder obtained with the objective of weighted interference minimization allows some multiuser interference in the system, and it is shown to improve the sum rate by 66% compared to a conventional zero forcing approach, for those users experiencing low signal to interference plus noise ratio