Electron beam evaporation of superconductor-ferromagnet heterostructures.

We report on the electronic and magnetic properties of superconductor-ferromagnet heterostructures fabricated by electron beam evaporation on to unheated thermally oxidised Si substrates. Polycrystalline Nb thin films (5 to 50 nm thick) were shown to possess reliably high superconducting critical temperatures ([Formula: see text]), which correlate well with the residual resistivity ratio (RRR) of the film. These properties improved during ex-situ annealing, resulting in [Formula: see text] and [Formula: see text]RRR increases of up 2.2 K ([Formula: see text] 40% of the pre-annealed [Formula: see text]) and 0.8 ([Formula: see text] 60% of the pre-annealed RRR) respectively. Nb/Pt/Co/Pt heterostructures showed substantial perpendicular anisotropy in the ultrathin limit (≤ 2.5 nm), even in the extreme limit of Pt(0.8 nm)/Co(1 nm)/Pt(0.6 nm). These results point to the use of electron beam evaporation as route to line-of-sight deposited, low-thickness, high quality Nb-based superspintronic multilayers.

The walking dead: sequential nuclear and organelle destruction during hair development.

BACKGROUND: Transition of hair shaft keratinocytes from actively respiring, nucleated cells to structural cells devoid of nucleus and cytoplasm is key to hair production. This form of cell 'death', or cornification, requires cellular organelle removal to allow the cytoplasm to become packed with keratin filament bundles that further require cross-linking to create a strong hair fibre. Although these processes are well described in epidermal keratinocytes, there is a lack of understanding of such mechanisms, specifically in the hair follicle. OBJECTIVES: To gain insights into cornification mechanisms within the hair follicle and thus improve our understanding of normal hair physiology. METHODS: Scalp biopsies and hair-pluck samples were obtained from healthy human donors and analysed microscopically after immunohistochemical staining. RESULTS: A focal point of respiratory activity was evident in keratogenous zone cells within the hair shaft, which also exhibited nuclear damage. Nuclear degradation occurred via both caspase-dependent and caspase-independent pathways. Conversely, mitophagy was driven by Bnip3L and restricted to the boundary of the keratogenous zone at Adamson's Fringe. CONCLUSIONS: We propose a model of stepwise living-dead transition within the first 1 mm of hair formation, whereby fully functional, nucleated cells first consolidate required functions by degrading nuclear DNA, yet continue to respire and provide the source of reactive oxygen species required for keratin cross-linking. Finally, as the cells become packed with keratin bundles, Bnip3L expression triggers mitophagy to rid the cells of the last remaining 'living' characteristic, thus completing the march from 'living' to 'dead' within the hair follicle.

A comparison of stress levels, coping styles and psychological morbidity between graduate-entry and traditional undergraduate medical students during the first 2 years at a UK medical school.

BACKGROUND: Stress levels and psychological morbidity are high among undergraduate medical students (UGs), but there is a lack of research into the psychological health of UK graduate-entry medical students (GEs). GEs are likely to experience different (perhaps more severe) stressors and to cope with stress differently. We compared stress levels, psychological morbidity and coping styles in GE versus UG medical students studying at the same UK medical school in the same academic year. A cross-sectional self-rated questionnaire study of all first- and second-year GE and UG medical students was conducted. Perceived stress, psychological morbidity, recent adverse life events, stress-related personality traits and coping styles were assessed using standard questionnaires. RESULTS: 75% GEs and 46% UGs responded to the questionnaire. Both groups reported equally high levels, and similar profiles of, perceived stress and psychological morbidity. Levels of recent adverse life events and stress-related personality traits were similar in both groups. Compared to UGs, GEs were more likely to use active coping (p = 0.02) and positive reframing (p = 0.03), but were also more likely to use substances (alcohol and other drugs; p < 0.001) to help them cope. Unlike UGs, second-year GEs showed less perceived stress (p = 0.007) and psychological morbidity (p = 0.006) than first-year GEs although levels of both were still high. CONCLUSION: Our results show that both GE students and their younger UG counterparts on a traditional medical course have similar profiles of stress symptoms. They do, however, cope with stress differently. GEs are more likely to use active problem-focused coping strategies, and they are also more likely to cope by using substances (alcohol or other drugs). GE students need interventions to prevent maladaptive coping styles and encourage adaptive coping that are tailored to their needs. Such interventions should be targeted at first-year students. It is vital that these students develop positive coping skills to benefit them during training and in a future career that is inherently stressful.

Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder.

We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10-8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2=0.35; BD II SNP-h2=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.

Cognitive mechanisms associated with auditory sensory gating.

Sensory gating is a neurophysiological measure of inhibition that is characterised by a reduction in the P50 event-related potential to a repeated identical stimulus. The objective of this work was to determine the cognitive mechanisms that relate to the neurological phenomenon of auditory sensory gating. Sixty participants underwent a battery of 10 cognitive tasks, including qualitatively different measures of attentional inhibition, working memory, and fluid intelligence. Participants additionally completed a paired-stimulus paradigm as a measure of auditory sensory gating. A correlational analysis revealed that several tasks correlated significantly with sensory gating. However once fluid intelligence and working memory were accounted for, only a measure of latent inhibition and accuracy scores on the continuous performance task showed significant sensitivity to sensory gating. We conclude that sensory gating reflects the identification of goal-irrelevant information at the encoding (input) stage and the subsequent ability to selectively attend to goal-relevant information based on that previous identification.

Patient navigation to increase colorectal cancer screening among Latino Medicare enrollees: a randomized controlled trial.

PURPOSE: Latino Medicare enrollees report suboptimal rates of colorectal cancer screening (CRCS) despite Medicare policies designed to improve CRCS access for older persons. Patient navigation (PN) may address many underlying barriers to CRCS, yet little is known about the effectiveness of PN to increase CRCS adherence among Latino Medicare enrollees. METHODS: Using a randomized controlled trial study design, we evaluated tailored PN delivered outside of primary care settings as an intervention to increase CRCS adherence in this population. Intervention participants (n = 135) received tailored PN services which included education, counseling, and logistical support administered in their language of choice. Comparison participants (n = 168) received mailed cancer education materials. We compared CRCS rates between interventions and used multivariable logistic regression to assess the odds of CRCS adherence for PN versus comparison groups after adjusting for covariates of interest. RESULTS: More navigated than non-navigated participants became CRCS adherent during the study period (43.7 vs. 32.1%, p = 0.04). The odds of CRCS adherence were significantly higher for PN relative to comparison participants before and after adjusting for covariates (unadjusted OR 1.64, p = 0.04; adjusted OR 1.82, p = 0.02). Higher CRCS adherence rates were observed primarily in the uptake of endoscopic screening methods. CONCLUSION: This study demonstrates that PN delivered outside of the primary care environment is modestly effective in increasing CRCS adherence among Latino Medicare enrollees. This intervention strategy should be further evaluated as a complement to primary care-based PN and other care coordination strategies to increase adherence with CRCS and other evidence-based screenings among older Latinos.

Rapid cycling as a feature of bipolar disorder and comorbid migraine.

BACKGROUND: Previous research has suggested the clinical profile of individuals with bipolar disorder (BD) differs according to the presence or absence of comorbid migraine. We aimed to determine the clinical characteristics that differentiate individuals with BD with and without comorbid migraine in a large, representative, clinically well-characterised UK sample. METHODS: The lifetime clinical characteristics of 1488 individuals with BD (BPI n=1120, BPII n=368) with and without comorbid migraine were compared (n=375 vs. n=1113 respectively). RESULTS: Individuals with BD and comorbid migraine had a distinctive set of lifetime clinical characteristics. A multivariate model showed that consistent with previous studies those with comorbid migraine were significantly more likely to be female (OR=2.099, p=0.005) and have comorbid panic attacks (OR=1.842, p=0.004). A novel finding was that even after controlling for other differences, the individuals with BD and comorbid migraine were more likely to have a rapid cycling illness course (OR=1.888, p=0.002). LIMITATIONS: Presence of migraine was assessed using self report measures. Cross-sectional study design limits investigations of bidirectional associations between migraine and bipolar disorder. CONCLUSIONS: Comorbid migraine in BD may represent a more homogenous subtype of BD with an unstable rapid cycling course. Identifying individuals with BD and comorbid migraine may be of use in a clinical setting and this subgroup could be the focus of future aetiological studies.

Echocardiogram study to evaluate the effect of the novel hepatitis C virus NS5A inhibitor GSK2336805 on cardiac contractility in healthy subjects.

GSK2336805 is a hepatitis C virus NS5A inhibitor in clinical development for the treatment of chronic hepatitis C virus infection. This was a single-center, randomized, double-blind, placebo-controlled, two-period crossover study in healthy adults to evaluate the effects of a single 150-mg dose of GSK2336805 on echocardiographic measures of contractility. GSK2336805 had no effect on ejection fraction, and there was no significant correlation between GSK2336805 plasma concentration and ejection fraction. (This study has been registered at Clinicaltrials.gov under registration no. NCT01424540.).

Safety, tolerability, pharmacokinetics, and antiviral activity of GSK2336805, an inhibitor of hepatitis C virus (HCV) NS5A, in healthy subjects and subjects chronically infected with HCV genotype 1.

GSK2336805 is an orally bioavailable hepatitis C virus (HCV) inhibitor working through an NS5A-mediated mechanism. This first-time-in-human study was conducted to assess the safety, tolerability, pharmacokinetics, metabolism, and efficacy of GSK2336805 in healthy subjects and subjects infected with HCV genotype 1. We performed a three-part, randomized, double-blind, placebo-controlled study in 46 healthy subjects and 23 HCV-infected subjects. After an overnight fast, healthy subjects received GSK2336805 as 10 mg, 30 mg, 30 mg plus food, and 60 mg in a single dose and 10 mg (7 days), 30 mg (7 days), and 75 mg (14 days) in a once-daily multiple dose. Subjects with HCV received GSK2336805 as a 1- to 120-mg single dose. In subjects with HCV, reductions in HCV RNA were observed within 4 h and a single dose of GSK2336805 of ≥10 mg resulted in a statistically significant ≥2-log reduction in HCV RNA compared with placebo at 24 h postdose. GSK2336805 was readily absorbed in all subjects, and the half-life (t1/2) was suitable for once-daily dosing. Administration of GSK2336805 with food had no effect on plasma GSK2336805 exposure; however, absorption was delayed, with a median tmax (time to maximum concentration of drug in serum) of 4.5 versus 2.0 h. Twenty subjects who received GSK2336805 experienced mild to moderate adverse events; none were serious. GSK2336805 was well tolerated and exhibited rapid, significant antiviral activity after a single dose in HCV-infected subjects. These results support the conduct of further studies evaluating GSK2336805 administered once daily for longer durations in combination with peginterferon, ribavirin, and other direct-acting antivirals. (This study has been registered at ClinicalTrials.gov under registration no. NCT01277692.).

Amelioration of the periparturient relaxation of immunity to parasites through a reduction in mammalian reproductive effort.

The degree of periparturient relaxation of immunity to gastrointestinal parasites has a nutritional basis, as overcoming protein scarcity through increased protein supply improves lactational performance, enhances local immune responses and reduces worm burdens. Herein lactating rats, re-infected with Nippostrongylus brasiliensis, are used to test the hypothesis that a similar and rapid improvement of immunity can be achieved through reducing nutrient demand at times of dietary protein scarcity. Reducing litter size from 12 to three pups during lactation resulted, as expected, in cessation of maternal body weight loss and increased pup body weight gain compared with dams which continued to nurse 12 pups. This increase in performance concurred with a rapid decrease in parasitism; within 3 days post nutrient reduction, a 87% reduction in the number of worm eggs found in the colon and 83% reduction in worm burdens was observed, which concurred with increased local immune responses, i.e. 70% more mast cells and 44% more eosinophils in the small intestinal mucosa, to levels similar to those in dams nursing three pups throughout. However, there were no concurrent changes in goblet cell hyperplasia, serum anti-N. brasiliensis-specific antibody levels or mRNA expression of IL-4, IL-10 or IL-13 in the mesenteric lymph nodes. To our knowledge the current study is the first to employ a litter reduction strategy to assess the rate of immune improvement upon overcoming nutrient scarcity in a non-ruminant host. These data support the hypothesis that periparturient relaxation of immunity to gastrointestinal nematodes can be reduced by restoring nutrient adequacy and, importantly, that this improvement can occur very rapidly.

Autologous incubated macrophage therapy in acute, complete spinal cord injury: results of the phase 2 randomized controlled multicenter trial.

STUDY DESIGN: Randomized controlled trial with single-blinded primary outcome assessment. OBJECTIVES: To determine the efficacy and safety of autologous incubated macrophage treatment for improving neurological outcome in patients with acute, complete spinal cord injury (SCI). SETTING: Six SCI treatment centers in the United States and Israel. METHODS: Participants with traumatic complete SCI between C5 motor and T11 neurological levels who could receive macrophage therapy within 14 days of injury were randomly assigned in a 2:1 ratio to the treatment (autologous incubated macrophages) or control (standard of care) groups. Treatment group participants underwent macrophage injection into the caudal boundary of the SCI. The primary outcome measure was American Spinal Injury Association (ASIA) Impairment Scale (AIS) A-B or better at ≥6 months. Safety was assessed by analysis of adverse events (AEs). RESULTS: Of 43 participants (26 treatment, 17 control) having sufficient data for efficacy analysis, AIS A to B or better conversion was experienced by 7 treatment and 10 control participants; AIS A to C conversion was experienced by 2 treatment and 2 control participants. The primary outcome analysis for subjects with at least 6 months follow-up showed a trend favoring the control group that did not achieve statistical significance (P=0.053). The mean number of AEs reported per participant was not significantly different between the groups (P=0.942). CONCLUSION: The analysis failed to show a significant difference in primary outcome between the two groups. The study results do not support treatment of acute complete SCI with autologous incubated macrophage therapy as specified in this protocol.

Blood feeding in juvenile Paragnathia formica (Isopoda: Gnathiidae): biochemical characterization of trypsin inhibitors, detection of anticoagulants, and molecular identification of fish hosts.

The 3 post-marsupial juvenile stages of the gnathiid isopod, Paragnathia formica, are haematophagous ectoparasites of fishes that may, in heavy infestations, cause host mortality. Protein digestion in fed stage 3 juveniles is accomplished by cysteine proteinases, but what bioactive compounds attenuate host haemostatic, inflammatory and immunological responses during feeding is unknown. Trypsin inhibitory activity and anticoagulant activity were detected in crude extracts of unfed P. formica stage 1 juveniles; fractionation of stage 1 crude extracts by ion exchange chromatography resulted in 3 preparations each displaying these bioactivities. Further characterization revealed anti-thrombin activity in 2 of these preparations, whilst the third displayed the strongest anticoagulant activity that targeted a factor of the intrinsic coagulation pathway. Three trypsin inhibitors (18 kDa, 21 kDa, and 22 kDa) were also detected using reverse zymography. In parallel, homogenates of fed stage 2 and 3 juveniles were used to identify their fish hosts by amplifying the 16S mitochondrial rDNA and 18S genomic rDNA vertebrate gene regions. Blood from at least 4 fish families had been ingested by separate individuals during feeding. This study demonstrates that trypsin inhibitors and anticoagulants are present in P. formica juveniles which could suppress host haemostatic, inflammatory and immunological responses during feeding, and that juveniles are not host specific.

The role of executive functions in human prospective interval timing.

Human timing is thought to be based on the output of an internal clock. Whilst the functioning of this clock is well documented, it is unclear which other cognitive resources may moderate timing. Brown (2006) and Rattat (2010) suggest that the central executive of working memory may be recruited during timing. However it seems likely that the fractionated executive component processes identified by Miyake et al. (2000) and Fisk and Sharp (2004) may differentially contribute to timing performance; further exploration of this was the aim of the present study. An interference paradigm was employed in which participants completed an interval production task, and tasks which have been shown to tap the four key executive component processes (shifting, inhibition, updating and access) under single and dual-task conditions. Comparison of single and dual-task performance indicated that timing always became more variable when concurrently performing a second task. Bidirectional interference only occurred between the interval production task and the memory updating task, implying that both tasks are competing for the same executive resource of updating. There was no evidence in the current study to suggest that switching, inhibition or access was involved in timing, however they may be recruited under more difficult task conditions.

Dissecting the impact of protein versus energy host nutrition on the expression of immunity to gastrointestinal parasites during lactation.

Many mammals exhibit a periparturient relaxation of previously established immune responses (PPRI) to gastrointestinal nematodes culminating in increased worm burdens. It has been suggested that the extent of PPRI may have a nutritional basis as it is considerably augmented when protein supply is scarce. Subsequent studies have shown that increased dietary protein intake can ameliorate this phenomenon. However, this effect is often confounded with increased food intake and thus increased energy levels. Herein, we aimed to dissect the effects of protein and energy nutrition on the immune status and resistance to re-infection with gastrointestinal nematodes in the periparturient host. The lactating, Nippostrongylus brasiliensis re-infected rat was utilised as an established model for mammalian PPRI. Experimental animals were assigned to restricted feeding regimens designed to achieve four pre-determined levels of crude protein (CP) at one of two levels of metabolisable energy (ME) and parasitological and immunological measurements taken at either day 6 or day 9 post re-infection. We clearly show that increased supply of dietary CP, but not increased dietary ME, significantly reduced worm burdens. The increased magnitude of worm expulsion with increased dietary CP supply strongly correlated with mucosal mast cell accumulation in the small intestine. In addition, increased CP and not ME supply increased mucosal eosinophil numbers. Furthermore, increased CP led to higher levels of total IgG at high ME only and there were interactive effects of CP and ME on serum levels of IgG1 and IgG2a. Perhaps surprisingly, CP nutrition did not affect expression of either Th1 (IFN-γ) or Th2 (IL-4, IL-13) cytokines in the mesenteric lymph nodes. These data emphasise the role of immunonutrition, and particularly dietary protein, in combating infectious disease such as gastrointestinal parasitism.

A new, passive dosemeter for gamma, beta and neutron radiations.

The Defence Science and Technology Laboratory (Dstl) provides personal radiation dosimetry to the UK Ministry of Defence. Dstl has recently developed a dosemeter that is based on a combination of thermoluminescent and etched-track detectors. The Dstl Combined Dosemeter is capable of assessing doses due to photons, beta particles and neutrons. This paper presents the laboratory type testing results for the Combined Dosemeter, and also describes the procedure for calibrating the dosemeter for use in workplace neutron fields. The Combined Dosemeter meets the type test requirements that are relevant to its intended applications, and gives neutron doses that are within 50% of the true dose in the workplaces in which it is used, even when the wearer has the potential to be exposed to a variety of neutron spectra (e.g. on board nuclear-powered submarines).

Tactile and Haptic Illusions.

This paper surveys the research literature on robust tactile and haptic illusions. The illusions are organized into two categories. The first category relates to objects and their properties, and is further differentiated in terms of haptic processing of material versus geometric object properties. The second category relates to haptic space, and is further differentiated in terms of the observer's own body versus external space. The illusions are initially described and where possible addressed in terms of their functional properties and/or underlying neural processes. The significance of these illusions for the design of tactile and haptic displays is also discussed. We conclude by briefly considering a number of important general themes that have emerged in the materials surveyed.

The neuropsychiatric phenotype in Darier disease.

BACKGROUND: Darier disease (DD) is a rare autosomal dominantly inherited skin disorder in which co-occurrence of neuropsychiatric abnormalities has been frequently reported by dermatologists. It is caused by mutations in a single gene, ATP2A2, which is expressed in the skin and brain. OBJECTIVES: To conduct the first systematic investigation of the neuropsychiatric phenotype in DD. METHODS: One hundred unrelated individuals with DD were assessed using a battery of standardized neuropsychiatric measures. Data were also obtained on a number of clinical features of DD. RESULTS: Individuals with DD were found to have high lifetime rates of mood disorders (50%), specifically major depression (30%) and bipolar disorder (4%), and suicide attempts (13%) and suicidal thoughts (31%). These were more common in DD when compared with general population data. The prevalence of epilepsy (3%) in the sample was also higher than the prevalence in the general population. There was no consistent association of specific dermatological features of DD and presence of psychiatric features. CONCLUSIONS: These findings highlight the need for clinicians to assess and recognize neuropsychiatric symptoms in DD. The results do not suggest that neuropsychiatric symptoms are simply a psychological reaction to having a skin disease, but are consistent with the pleiotropy hypothesis that mutations in the ATP2A2 gene, in addition to causing DD, confer susceptibility to neuropsychiatric features. Further research is needed to investigate genotype-phenotype correlations between the types and/or locations of pathogenic mutations within ATP2A2 and the expressed neuropsychiatric phenotypes.

A phase 2 autologous cellular therapy trial in patients with acute, complete spinal cord injury: pragmatics, recruitment, and demographics.

STUDY DESIGN: Post hoc analysis from a randomized controlled cellular therapy trial in acute, complete spinal cord injury (SCI). OBJECTIVES: Description and quantitative review of study logistics, referral patterns, current practice patterns and subject demographics. SETTING: Subjects were recruited to one of six international study centers. METHODS: Data are presented from 1816 patients pre-screened, 75 participants screened and 50 randomized. RESULTS: Of the 1816 patients pre-screened, 53.7% did not meet initial study criteria, primarily due to an injury outside the time window (14 days) or failure to meet neurological criteria (complete SCI between C5 motor/C4 sensory and T11). MRIs were obtained on 339 patients; 51.0% were ineligible based on imaging criteria. Of the 75 participants enrolled, 25 failed screening (SF), leaving 50 randomized. The primary reason for SF was based on the neurological exam (51.9%), followed by failure to meet MRI criteria (22.2%). Of the 50 randomized subjects, there were no significant differences in demographics in the active versus control arms. In those participants for whom data was available, 93.8% (45 of 48) of randomized participants received steroids before study entry, whereas 94.0% (47 of 50) had spine surgery before study enrollment. CONCLUSION: The 'funnel effect' (large numbers of potentially eligible participants with a small number enrolled) impacts all trials, but was particularly challenging in this trial due to eligibility criteria and logistics. Data collected may provide information on current practice patterns and the issues encountered and addressed may facilitate design of future trials.

Magnesium sulphate in the treatment of acute asthma: evaluation of current practice in adult emergency departments.

BACKGROUND: A recent meta-analysis showed that intravenous and nebulised magnesium sulphate have similar levels of evidence to support their use in the treatment of acute asthma in adults. This consisted of weak evidence of effect on respiratory function and hospital admissions, with wide confidence intervals ranging from no effect to significant positive effects. Current BTS/SIGN guidelines suggest an equivocal role for intravenous magnesium sulphate and no role for nebulised magnesium sulphate. A study was performed to assess what emergency physicians currently do in their management of acute asthma. METHOD: A postal survey was undertaken of all adult emergency departments within the UK. A structured questionnaire was sent to all clinical leads in emergency medicine about their current usage of both intravenous and nebulised magnesium sulphate in the treatment of acute asthma. RESULTS: 180 of the 251 emergency departments in the UK responded (72%). Magnesium sulphate was used in 93%, mostly because it was expected to relieve breathlessness (70%) or reduce HDU/ITU admissions (51%). It was predominantly given to those patients with acute severe asthma (84%) and life-threatening exacerbations (87%), with most stating they would give the drug if there was no response to repeated nebulisers (68%). In comparison, nebulised magnesium sulphate was only used in two emergency departments (1%). The main reason for not administering the drug via a nebuliser was insufficient evidence (51%). CONCLUSIONS: Intravenous magnesium sulphate is widely used for acute asthma, usually for patients with severe or life-threatening asthma who have not responded to initial treatment. Nebulised magnesium sulphate, by contrast, is hardly used at all. The use of intravenous magnesium sulphate is more extensive than current guidelines or available evidence would appear to support.

Immunomodulatory effects of dietary protein during Nippostrongylus brasiliensis re-infection in lactating rats.

Periparturient relaxation of immunity (PPRI) to secondary infection with nematodes is believed to have a nutritional basis due to differential partitioning of scarce nutrient resources, particularly protein, to reproductive rather than immune functions. At times of protein scarcity, an increase in protein supply has been reported to assuage this phenomenon. The Nippostrongylus brasiliensis reinfected lactating rat model is now being utilized to investigate the immune reactions underlying the modifying role of dietary protein on PPRI. Herein, we demonstrate that lactating rats reinfected with N. brasiliensis under high protein (HP) dietary conditions exhibit decreased worm burdens and reduced colon egg counts compared to their low protein (LP) counterparts. These reductions correlated with increased mastocytosis and greater goblet cell hyperplasia. Additionally, the local antibody profile revealed that HP reinfected lactating rats developed a stronger antigen specific IgG2b response earlier in infection in comparison with their LP counterparts. Our study provides evidence that increased dietary protein content reduces the PPRI to N. brasiliensis re-infection in the lactating rat through improved mucosal immune responses.