Nurse-led Preoperative Education With Home-based Internet Resources for Pediatric Patients and Their Parents.

The majority of pediatric patients and their parents experience fear and anxiety related to their surgical experience. Traditionally, anesthesia providers addressed this anxiety with pharmacologic therapy, such as benzodiazepines, to provide amnesia and anxiolysis. However, this approach has been questioned due to the potential for developmental neurotoxicity, among other drawbacks. Further, the pharmacological approach does not remove preexisting anxiety that the child and parent experience before arrival and during check-in. Pediatric and parental preparation before surgery is an important step that continues to be inconsistently addressed, particularly in lower-resource community hospitals where the majority of routine pediatric outpatient procedures occur. This care gap provides an opportunity for preanesthesia nurses to intervene with valid, evidence-based preoperative education tools aimed at pediatric patients and their parents. Providing these resources before the day of surgery allows time for child-directed, at-home practice as often as the parent(s) and patient choose. Use of available resources from a leading children's hospital, nurses can create a tailored, developmentally appropriate preoperative education plan for pediatric patients and their parents, providing families with the power to create a positive surgical experience.

Integrating genomics and multiplatform metabolomics enables metabolite quantitative trait loci detection in breeding-relevant apple germplasm.

Apple (Malus × domestica) has commercial and nutritional value, but breeding constraints of tree crops limit varietal improvement. Marker-assisted selection minimises these drawbacks, but breeders lack applications for targeting fruit phytochemicals. To understand genotype-phytochemical associations in apples, we have developed a high-throughput integration strategy for genomic and multiplatform metabolomics data. Here, 124 apple genotypes, including members of three pedigree-connected breeding families alongside diverse cultivars and wild selections, were genotyped and phenotyped. Metabolite genome-wide association studies (mGWAS) were conducted with c. 10 000 single nucleotide polymorphisms and phenotypic data acquired via LC-MS and 1 H NMR untargeted metabolomics. Putative metabolite quantitative trait loci (mQTL) were then validated via pedigree-based analyses (PBA). Using our developed method, 519, 726 and 177 putative mQTL were detected in LC-MS positive and negative ionisation modes, and NMR, respectively. mQTL were indicated on each chromosome, with hotspots on linkage groups 16 and 17. A chlorogenic acid mQTL was discovered on chromosome 17 via mGWAS and validated with a two-step PBA, enabling discovery of novel candidate gene-metabolite relationships. Complementary data from three metabolomics approaches and dual genomics analyses increased confidence in validity of compound annotation and mQTL detection. Our platform demonstrates the utility of multiomic integration to advance data-driven, phytochemical-based plant breeding.

Evaluating the effect of roasting on coffee lipids using a hybrid targeted-untargeted NMR approach in combination with MRI.

An integrated targeted-untargeted 1H and 13C Nuclear Magnetic Resonance (NMR) analysis was applied to determine the impact of roasting on coffee lipids. For targeted analysis, both an internal standard (IS) method, as well as the ERETIC2 tool based on PULCON (Pulse Length-based Concentration determination), were used for quantitation. PULCON allows for quantitative analysis without sample contamination with an IS and was found to be in very good agreement with the traditional IS approach as indicated by a systematic Bland-Altman comparison study. For the untargeted analysis, NMR was coupled with multivariate statistical analysis (MVSA), namely Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), and Orthogonal Projection to Latent Structures Discriminant Analysis (OPLS-DA). 13C NMR spectra were acquired using a z-stored spin-echo sequence to achieve higher spectral quality, which is important for both targeted and untargeted analysis. Results showed that roasting has a clear effect on coffee lipids, with diterpenes, oxidation/hydrolysis products and unsaturated fatty acid chains being the most significant markers. In addition, the application of MRI indicated important morphological alterations in bean structure and lipid migration from the endosperm to the surface of the coffee bean.

NMR analysis of roasted coffee lipids and development of a spent ground coffee application for the production of bioplastic precursors.

Multinuclear and multidimensional NMR spectroscopy was applied as a robust and rapid tool for the analysis of several classes of non-polar compounds in roasted coffee beans, coffee beverage and spent coffee grounds. In addition to various fatty acids, other compounds found in roasted coffee lipids, include oxidation and hydrolysis products, terpenes, sterols, and phospholipids. Spent coffee grounds have a similar fatty acid composition with roasted coffee beans and they are rich in Cafestol and Kawheol, which appear as esters of fatty acids. Triglycerides extracted from coffee waste using a green chemistry approach, based on supercritical CO2 extraction, are promising candidates for the production of bioplastics. Bioplastic precursors were produced using an in situ solvent-free epoxidation process and the reaction monitoring was performed using NMR spectroscopy.

Insulin for the treatment of women with gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with short- and long-term complications for the mother and her infant. Women who are unable to maintain their blood glucose concentration within pre-specified treatment targets with diet and lifestyle interventions will require anti-diabetic pharmacological therapies. This review explores the safety and effectiveness of insulin compared with oral anti-diabetic pharmacological therapies, non-pharmacological interventions and insulin regimens. OBJECTIVES: To evaluate the effects of insulin in treating women with gestational diabetes. SEARCH METHODS: We searched Pregnancy and Childbirth's Trials Register (1 May 2017), ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (1 May 2017) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (including those published in abstract form) comparing:a) insulin with an oral anti-diabetic pharmacological therapy;b) with a non-pharmacological intervention;c) different insulin analogues;d) different insulin regimens for treating women with diagnosed with GDM.We excluded quasi-randomised and trials including women with pre-existing type 1 or type 2 diabetes. Cross-over trials were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, risk of bias, and extracted data. Data were checked for accuracy. MAIN RESULTS: We included 53 relevant studies (103 publications), reporting data for 7381 women. Forty-six of these studies reported data for 6435 infants but our analyses were based on fewer number of studies/participants.Overall, the risk of bias was unclear; 40 of the 53 included trials were not blinded. Overall, the quality of the evidence ranged from moderate to very low quality. The primary reasons for downgrading evidence were imprecision, risk of bias and inconsistency. We report the results for our maternal and infant GRADE outcomes for the main comparison. Insulin versus oral anti-diabetic pharmacological therapyFor the mother, insulin was associated with an increased risk for hypertensive disorders of pregnancy (not defined) compared to oral anti-diabetic pharmacological therapy (risk ratio (RR) 1.89, 95% confidence interval (CI) 1.14 to 3.12; four studies, 1214 women; moderate-quality evidence). There was no clear evidence of a difference between those who had been treated with insulin and those who had been treated with an oral anti-diabetic pharmacological therapy for the risk of pre-eclampsia (RR 1.14, 95% CI 0.86 to 1.52; 10 studies, 2060 women; moderate-quality evidence); the risk of birth by caesarean section (RR 1.03, 95% CI 0.93 to 1.14; 17 studies, 1988 women; moderate-quality evidence); or the risk of developing type 2 diabetes (metformin only) (RR 1.39, 95% CI 0.80 to 2.44; two studies, 754 women; moderate-quality evidence). The risk of undergoing induction of labour for those treated with insulin compared with oral anti-diabetic pharmacological therapy may possibly be increased, although the evidence was not clear (average RR 1.30, 95% CI 0.96 to 1.75; three studies, 348 women; I² = 32%; moderate-quality of evidence). There was no clear evidence of difference in postnatal weight retention between women treated with insulin and those treated with oral anti-diabetic pharmacological therapy (metformin) at six to eight weeks postpartum (MD -1.60 kg, 95% CI -6.34 to 3.14; one study, 167 women; low-quality evidence) or one year postpartum (MD -3.70, 95% CI -8.50 to 1.10; one study, 176 women; low-quality evidence). The outcomes of perineal trauma/tearing or postnatal depression were not reported in the included studies.For the infant, there was no evidence of a clear difference between those whose mothers had been treated with insulin and those treated with oral anti-diabetic pharmacological therapies for the risk of being born large-for-gestational age (average RR 1.01, 95% CI 0.76 to 1.35; 13 studies, 2352 infants; moderate-quality evidence); the risk of perinatal (fetal and neonatal death) mortality (RR 0.85; 95% CI 0.29 to 2.49; 10 studies, 1463 infants; low-quality evidence);, for the risk of death or serious morbidity composite (RR 1.03, 95% CI 0.84 to 1.26; two studies, 760 infants; moderate-quality evidence); the risk of neonatal hypoglycaemia (average RR 1.14, 95% CI 0.85 to 1.52; 24 studies, 3892 infants; low-quality evidence); neonatal adiposity at birth (% fat mass) (mean difference (MD) 1.6%, 95% CI -3.77 to 0.57; one study, 82 infants; moderate-quality evidence); neonatal adiposity at birth (skinfold sum/mm) (MD 0.8 mm, 95% CI -2.33 to 0.73; random-effects; one study, 82 infants; very low-quality evidence); or childhood adiposity (total percentage fat mass) (MD 0.5%; 95% CI -0.49 to 1.49; one study, 318 children; low-quality evidence). Low-quality evidence also found no clear differences between groups for rates of neurosensory disabilities in later childhood: hearing impairment (RR 0.31, 95% CI 0.01 to 7.49; one study, 93 children), visual impairment (RR 0.31, 95% CI 0.03 to 2.90; one study, 93 children), or any mild developmental delay (RR 1.07, 95% CI 0.33 to 3.44; one study, 93 children). Later infant mortality, and childhood diabetes were not reported as outcomes in the included studies.We also looked at comparisons for regular human insulin versus other insulin analogues, insulin versus diet/standard care, insulin versus exercise and comparisons of insulin regimens, however there was insufficient evidence to determine any differences for many of the key health outcomes. Please refer to the main results for more information about these comparisons. AUTHORS' CONCLUSIONS: The main comparison in this review is insulin versus oral anti-diabetic pharmacological therapies. Insulin and oral anti-diabetic pharmacological therapies have similar effects on key health outcomes. The quality of the evidence ranged from very low to moderate, with downgrading decisions due to imprecision, risk of bias and inconsistency.For the other comparisons of this review (insulin compared with non-pharmacological interventions, different insulin analogies or different insulin regimens), there is insufficient volume of high-quality evidence to determine differences for key health outcomes.Long-term maternal and neonatal outcomes were poorly reported for all comparisons.The evidence suggests that there are minimal harms associated with the effects of treatment with either insulin or oral anti-diabetic pharmacological therapies. The choice to use one or the other may be down to physician or maternal preference, availability or severity of GDM. Further research is needed to explore optimal insulin regimens. Further research could aim to report data for standardised GDM outcomes.

NMR Spectroscopy as a Robust Tool for the Rapid Evaluation of the Lipid Profile of Fish Oil Supplements.

The western diet is poor in n-3 fatty acids, therefore the consumption of fish oil supplements is recommended to increase the intake of these essential nutrients. The objective of this work is to demonstrate the qualitative and quantitative analysis of encapsulated fish oil supplements using high-resolution 1H and 13C NMR spectroscopy utilizing two different NMR instruments; a 500 MHz and an 850 MHz instrument. Both proton (1H) and carbon (13C) NMR spectra can be used for the quantitative determination of the major constituents of fish oil supplements. Quantification of the lipids in fish oil supplements is achieved through integration of the appropriate NMR signals in the relevant 1D spectra. Results obtained by 1H and 13C NMR are in good agreement with each other, despite the difference in resolution and sensitivity between the two nuclei and the two instruments. 1H NMR offers a more rapid analysis compared to 13C NMR, as the spectrum can be recorded in less than 1 min, in contrast to 13C NMR analysis, which lasts from 10 min to one hour. The 13C NMR spectrum, however, is much more informative. It can provide quantitative data for a greater number of individual fatty acids and can be used for determining the positional distribution of fatty acids on the glycerol backbone. Both nuclei can provide quantitative information in just one experiment without the need of purification or separation steps. The strength of the magnetic field mostly affects the 1H NMR spectra due to its lower resolution with respect to 13C NMR, however, even lower cost NMR instruments can be efficiently applied as a standard method by the food industry and quality control laboratories.

Computer-determined dosage of insulin in the management of neonatal hyperglycaemia (HINT2): protocol of a randomised controlled trial.

INTRODUCTION: Neonatal hyperglycaemia is frequently treated with insulin, which may increase the risk of hypoglycaemia. Computer-determined dosage of insulin (CDD) with the STAR-GRYPHON program uses a computer model to predict an effective dose of insulin to treat hyperglycaemia while minimising the risk of hypoglycaemia. However, CDD models can require more frequent blood glucose testing than common clinical protocols. The aim of this trial is to determine if CDD using STAR-GRYPHON reduces hypoglycaemia in hyperglycaemic preterm babies treated with insulin independent of the frequency of blood glucose testing. METHODS AND ANALYSIS: Design: Multicentre, non-blinded, randomised controlled trial. SETTING: Neonatal intensive care units in New Zealand and Australia. PARTICIPANTS: 138 preterm babies ≤30 weeks' gestation or ≤1500 g at birth who develop hyperglycaemia (two consecutive blood glucose concentrations ≥10 mmol/L, at least 4 hours apart) will be randomised to one of three groups: (1) CDD using the STAR-GRYPHON model-based decision support system: insulin dose and frequency of blood glucose testing advised by STAR-GRYPHON, with a maximum testing interval of 4 hours; (2) bedside titration: insulin dose determined by medical staff, maximum blood glucose testing interval of 4 hours; (3) standard care: insulin dose and frequency of blood glucose testing determined by medical staff. The target range for blood glucose concentrations is 5-8 mmol/L in all groups. A subset of babies will have masked continuous glucose monitoring. PRIMARY OUTCOME: is the number of babies with one or more episodes of hypoglycaemia (blood glucose concentration <2.6 mmol/L), during treatment with insulin. ETHICS AND DISSEMINATION: This protocol has been approved by New Zealand's Health and Disability Ethics Committee: 14/STH/26. A data safety monitoring committee has been appointed to oversee the trial. Findings will be disseminated to participants and carers, peer-reviewed journals, guideline developers and the public. TRIAL REGISTRATION NUMBER: 12614000492651.

Clinical outcome and predictors of adverse events of an enhanced older adult psychiatric liaison service: Rapid Assessment Interface and Discharge (Newport).

BACKGROUND: Hospitals are currently admitting an increasing number of older people, and more than one-third could have an underlying mental health problem. The existing Older Adult Mental Health (OAMH) liaison service was increasingly unable to meet the escalating needs of older and frail patients. Therefore, the service was modernized and enhanced on an "invest-to-save" principle to provide a prompt holistic assessment for older adults with mental health problems. The objective of this study was a service evaluation to appraise clinical outcome, minimize the length of stay, and measure the predictors of adverse outcomes to streamline this enhanced service. MATERIALS AND METHODS: Patient demographics, social care needs, comorbidity burden (Charlson comorbidity index, CCI), and functional status (Barthel index, BI) were recorded from November 2014 to February 2015. Frailty status (frailty index, FI) was measured by an index (Rockwood index) of accumulated deficits. The outcomes were compared with the previous OAMH liaison service data over the same period a year earlier. RESULTS: The new Rapid Assessment Interface and Discharge service assessed 339 patients compared to 179 by the previous liaison team over the 4-month period. Mean age was 82.18±8.04 years, with 60% women; preadmission BI was 14.96±4.35, and admission BI was 11.38±5.73 (P<0.001, paired t-test); mean CCI was 1.66±1.53, and mean FI was 0.34±0.99, and 80% were on polypharmacy. The direct discharges from front door were increased by 7%. The mean hospital stay reduced from 35 to 20 days in acute site and from 108 to 47 days in long-stay wards. The cost benefits were based on the mean reduction in hospital stay (41.8 days) and admission reduction (2.2 days), leading to a total annualized bed savings of 44 days. FI was the most highly significant factor between patient groups with a good and poor outcome (P=0.00003, independent groups t-test, t=-4.38, df 98). CONCLUSION: Prompt mental health assessments for acutely unwell frail older people are not only cost effective but also improve clinical outcomes.

The use of dextrose/insulin infusions during labour and delivery in women with gestational diabetes mellitus: Is there any point?

We compared, in 733 women with gestational diabetes mellitus treated with metformin and/or insulin, rates of neonatal hypoglycaemia in those who had received a dextrose/insulin infusion during labour and prior to delivery (n = 132) with those who did not (n = 601). Women who had infusions were more likely to have been treated with insulin (87.1% vs 70.4%, P < 0.01) and have higher mean capillary glucose values (measured four times daily) in the two weeks prior to delivery (P < 0.01). They had lower mean (SD) glucose values in the 12 h prior to delivery (5.1 (1.1) mmol/L vs 5.4 (0.9) mmol/L, P < 0.01). There was no difference between the groups in rates of neonatal hypoglycaemia (glucose <2.6 mmol/L on two or more occasions), 15.9% versus 17.8%, P = 0.78, or of severe neonatal hypoglycaemia (one or more glucose <1.6 mmol/L), 8.3% versus 5.2%, P = 0.15. In the absence of randomised data comparing use of infusions with no infusions, these data are reassuring for clinicians who do not routinely use infusions.

High-throughput screening platform identifies small molecules that prevent sequestration of Plasmodium falciparum-infected erythrocytes.

BACKGROUND: We developed a 2-step approach to screen molecules that prevent and/or reverse Plasmodium falciparum-infected erythrocyte (IE) binding to host receptors. IE adhesion and sequestration in vasculature causes severe malaria, and therefore antiadhesion therapy might be useful as adjunctive treatment. IE adhesion is mediated by the polymorphic family (approximately 60 members) of P. falciparum EMP1 (PfEMP1) multidomain proteins. METHODS: We constructed sets of PfEMP1 domains that bind ICAM-1, CSA, or CD36, receptors that commonly support IE binding. Combinations of domain-coated beads were assayed by Bio-Plex technology as a high-throughput molecular platform to screen antiadhesion molecules (antibodies and small molecules). Molecules identified as so-called hits in the screen (first step) then could be assayed individually for inhibition of binding of live IE to receptors (second step). RESULTS: In proof-of-principle studies, the antiadhesion activity of several antibodies was concordant in Bio-Plex and live IE assays. Using this 2-step approach, we identified several molecules in a small molecule library of 10 000 compounds that could inhibit and reverse binding of IEs to ICAM-1 and CSA receptors. CONCLUSION: This 2-step screening approach should be efficient for identification of antiadhesion drug candidates for falciparum malaria.

Antigen-presenting phagocytic cells ingest malaria parasites and increase HIV replication in a tumor necrosis factor α-dependent manner.

BACKGROUND: Plasmodium falciparum infection induces human immunodeficiency virus (HIV) replication and accelerates a decline in CD4(+) T-cell count. The mechanisms contributing to these interactions have not been fully elucidated. METHODS: We infected peripheral blood mononuclear cells (PBMCs) with HIV type 1 (HIV-1) and then cocultured them with P. falciparum-infected red blood cells (iRBCs) or uninfected RBCs (uRBCs). Levels of HIV-1 p24 antigen and activation-associated cytokines were measured in culture supernatants. T-cell surface activation was assessed by flow cytometry. RESULTS: It has been reported that iRBCs increase HIV replication, compared with uRBCs; that neutralizing tumor necrosis factor α (TNF-α) abrogates this increase; and that hemozoin enhances HIV production. In this study, we confirmed that TNF-α plays an important role in this interaction. We show that iRBCs increased CD4(+) T-cell expression of HLA-DR(+)/CD38(+) (P = .001), that monocyte/macrophage depletion reduced HIV production by 40%-50% (P < .001), and that hemozoin-laden monocytes/macrophages that were preincubated with iRBCs also stimulated HIV production. CONCLUSIONS: iRBCs activate CD4(+) T cells and stimulate HIV replication in a TNF-α-dependent manner following malarial antigen processing by monocytes/macrophages. These results suggest that the persistent elevation of HIV replication during and after acute bouts of P. falciparum malaria may be due, at least in part, to ongoing stimulation of CD4(+) T cells by hemozoin-loaded antigen-presenting cells within lymphoid tissues.

Social attribution skills of children born preterm at very low birth weight.

Children born prematurely at very low birth weight (<1500 g) are at increased risk for impairments affecting social functioning, including autism spectrum disorders (e.g., Johnson et al., 2010). In the current study, we used the Happé-Frith animated triangles task (Abell, Happé, & Frith, 2000) to study social attribution skills in this population. In this task, typical viewers attribute intentionality and mental states to shapes, based on characteristics of their movements. Participants included 34 preterm children and 36 full-term controls, aged 8-11 years. Groups were comparable in terms of age at test, gender, handedness, and socioeconomic status; they also performed similarly on tests of selective attention/processing speed and verbal intelligence. Relative to full-term peers, preterm children's descriptions of the animations were less appropriate overall; they also overattributed intentionality/mental states to randomly moving shapes and underattributed intentionality/mental states to shapes that seemed to be interacting socially. Impairments in the ability to infer the putative mental states of triangles from movement cues alone were most evident in children displaying more "autistic-like" traits, and this may reflect atypical development of and/or functioning in, or atypical connections between, parts of the social brain.

Social perception in children born at very low birthweight and its relationship with social/behavioral outcomes.

BACKGROUND: Research has shown that children born very prematurely are at substantially elevated risk for social and behavioral difficulties similar to those seen in full-term children with autism spectrum disorders (ASDs). METHODS: To gain insight into core deficits that may underlie these difficulties, in this study, we assessed the social perceptual skills of 8- to 11-year-old children born at very low birthweight (VLBW) (<1,500 g) and age-matched, full-term controls, using the Child and Adolescent Social Perception Measure. We also assessed social and behavioral outcomes with two parent-report measures used in ASD screening. RESULTS: Children in the preterm group had normal range estimated verbal IQ. However, we found that they were impaired in their ability to use nonverbal cues from moving faces and bodies, and situational cues, to correctly identify the emotions of characters depicted in videotaped social interactions. Their performance on this task was related to the number of 'autistic-like' traits they displayed. CONCLUSIONS: This research highlights links between social perceptual deficits and poor social and behavioral outcomes in children born very prematurely. The results also suggest that even those who have escaped major intellectual/language problems are at risk for social and behavioral problems that can be of clinical concern.

The Rapid Assessment Interface and Discharge service and its implications for patients with dementia.

The rising prevalence of dementia will have an effect on acute care hospitals around the world. At present, around 40% of patients older than 70 years with acute medical admissions have dementia, but only half of these patients have been diagnosed. Patients with dementia have poorer health outcomes, longer hospital stays, and higher rates of readmissions and institutionalization. Worldwide, health care budgets are severely constrained. National Institute for Health and Care Excellence (NICE) has listed ten quality standards for supporting people in living well with dementia. NICE resource implications and commissioning support to implement these guidelines and improve dementia services have been recently published. Although most of the frail elderly patients with dementia are cared for by geriatricians, obstacles to making a diagnosis and to the management of dementia have been recognized. To provide a timely diagnosis of dementia, better care in acute hospital settings, and continuity of care in the community, services integrating all these elements are warranted. Extra resources also will be required for intermediate, palliative care, and mental health liaison services for people with dementia. The Birmingham Rapid Assessment Interface and Discharge service model uses a multiskilled team that provides comprehensive assessment of a person's physical and psychological well-being in a general hospital setting. It has been shown to be an effective model in terms of reducing both length of stay and avoiding readmission. The aim of this review is to discuss the implications of the Rapid Assessment Interface and Discharge model in people with dementia and to critically compare this model with similar published service provisions.

Multilaboratory approach to preclinical evaluation of vaccine immunogens for placental malaria.

Pregnancy malaria is caused by Plasmodium falciparum-infected erythrocytes that adhere to the placental receptor chondroitin sulfate A (CSA) and sequester in the placenta; women become resistant to pregnancy malaria as they acquire antiadhesion antibodies that target surface proteins of placental parasites. VAR2CSA, a member of the P. falciparum EMP1 variant surface antigen family, is the leading candidate for a pregnancy malaria vaccine. Because VAR2CSA is a high-molecular-weight protein, a vaccine based on the full-length protein may not be feasible. An alternative approach has been to develop a vaccine targeting individual Duffy binding-like (DBL) domains. In this study, a consortium of laboratories under the Pregnancy Malaria Initiative compared the functional activity of antiadhesion antibodies elicited by different VAR2CSA domains and variants produced in prokaryotic and eukaryotic expression systems. Antisera were initially tested against laboratory lines of maternal parasites, and the most promising reagents were evaluated in the field against fresh placental parasite samples. Recombinant proteins expressed in Escherichia coli elicited antibody levels similar to those expressed in eukaryotic systems, as did the two allelic forms of the DBL4 and DBL5 domains. The procedures developed for this head-to-head comparison will be useful for future evaluation and down-selection of malaria vaccine immunogens.

Real-time quantitative reverse transcription PCR for monitoring of blood-stage Plasmodium falciparum infections in malaria human challenge trials.

To detect pre-patent parasitemia, we developed a real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for the asexual 18S ribosomal RNA (rRNAs) of Plasmodium falciparum. Total nucleic acids extracted from whole blood were combined with control RNA and tested by qRT-PCR. The assay quantified > 98.7% of parasite-containing samples to ±0.5 log(10) parasites/mL of the nominal value without false positives. The analytical sensitivity was ≥ 20 parasites/mL. The coefficient of variation was 0.6% and 1.8% within runs and 1.6% and 4.0% between runs for high and low parasitemia specimens, respectively. Using this assay, we determined that A-type 18S rRNAs are stably expressed at 1 × 10(4) copies per ring-stage parasite. When used to monitor experimental P. falciparum infection of human volunteers, the assay detected blood-stage infections 3.7 days earlier on average than thick blood smears. This validated, internally controlled qRT-PCR method also uses a small (50 µL) sample volume requiring minimal pre-analytical handling, making it useful for clinical trials.

Male attractiveness regulates daughter fecundity non-genetically via maternal investment.

Mothers can non-genetically influence offspring phenotype in response to environmental conditions, including mate attractiveness. If such 'maternal effects' influence the offspring's reproduction and F2 generation, there is a mechanism for non-genetic trans-generational effects on phenotype, including epigenetic phenomena, with implications for evolution and population dynamics. We demonstrate in the zebra finch Taeniopygia guttata such non-genetic effects on offspring fecundity and the size of early stage F2 (eggs) in response to experimentally manipulated father's attractiveness. Our experimental design allowed us to deduce that the mechanism for this non-genetic paternal effect was via maternal investment in eggs. This affected female offspring size and, consequently, fecundity and F2 (egg) size. This demonstrates that female perception of mate attractiveness can have non-genetic, trans-generational fitness consequences and this may have important implications for the evolution of sexually selected traits and population dynamics.

Patients' perceptions of the process of consenting to electroconvulsive therapy.

BACKGROUND: The concept of valid consent has become important for electroconvulsive therapy (ECT). However, many patients feel that they do not have enough information before consenting and a significant minority feel coerced into consenting. Little is known about what factors account for these views. AIM: To explore patients' perceptions about how they consented to ECT. METHOD: Twelve participants were interviewed about their experiences of consenting to ECT. Interviews were subjected to a thematic analysis. RESULTS: Participants' perceptions of consenting to ECT were complex, and interpersonal factors were found to be important. Many participants felt that they had consented without adequate information from medical sources and that they had little choice to agree. Two participants consented to ECT as either a form of self-harm or hoping it would kill them. CONCLUSION: Consenting to ECT is more complex than currently recognised and involves interpersonal and systemic factors. As a result, people may consent because they feel that they have little choice. Implications for practice are discussed.

A novel presenilin 1 mutation, I202F occurring at a previously predicted pathogenic site causing autosomal dominant Alzheimer's disease.

We report a novel presenilin-1 (PSEN1) mutation, I202F occurring in a Welsh kindred with familial Alzheimer's disease. The average age at onset was 53 years. The I202F mutation occurs in alignment with previously reported PSEN1 mutations in the fourth transmembrane domain and confirms that PSEN1 mutations line up along transmembrane alpha-helices.

Immunization with VAR2CSA-DBL5 recombinant protein elicits broadly cross-reactive antibodies to placental Plasmodium falciparum-infected erythrocytes.

Pregnancy-associated malaria is a severe clinical syndrome associated with the sequestration of Plasmodium falciparum-infected erythrocytes in the placenta. Placental binding is mediated by VAR2CSA, a member of the large and diverse P. falciparum erythrocyte membrane 1 (PfEMP1) protein family. To better understand if conserved regions in VAR2CSA can be targeted by antibodies, we immunized rabbits with VAR2CSA-DBL1 and -DBL5 recombinant proteins produced in Pichia pastoris and developed a panel of seven chondroitin sulfate A (CSA)-binding parasites from diverse geographic origins. Overall, no two parasites in the panel expressed the same VAR2CSA sequence. The DBL1 domains averaged 80% amino acid identity (range, 72 to 89%), and the DBL5 domains averaged 86% amino acid identity (range, 83 to 99%), similar to a broader sampling of VAR2CSA sequences from around the world. Whereas antibodies generated against the VAR2CSA-DBL1 recombinant protein had only limited breadth and reacted with three or four parasites in the panel, immunization with DBL5 recombinant proteins elicited broadly cross-reactive antibodies against all or most parasites in the panel, as well as to fresh clinical isolates from pregnant women. These findings demonstrate that the major PfEMP1 variant expressed by placental isolates exposes strain-transcendent epitopes that can be targeted by vaccination and may have application for pregnancy malaria vaccine development.