Low molecular weight measles immunoglobulin M in subacute sclerosing panencephalitis and acute measles

Thirty eight patients with subacute sclerosing panencephalitis (SSPE) were investigated. Five patients who previously had measles immunoglobulin M (IgM) detected in unfractionated serum and cerebrospinal fluid (CSF) had measles IgM exclusively in the low molecular weight (LMW) fractions of serum and CSF. Measles IgM had previously not been found in unfractionated serum from 33 patients but was detected exclusively in the LMW fractions of serum from 30 patients. Seven children with acute measles had the expected high molecular weight (HMW) measles IgM in serum but 5 also had LMW measles IgM. Four young adults who had had measles in childhood had neither HMW nor LMW measles IgM in their sera.

An evaluation of the capability of a biolayer interferometry biosensor to detect low-molecular-weight food contaminants

The safety of our food is an essential requirement of society. One well-recognised threat is that of chemical contamination of our food, where low-molecular-weight compounds such as biotoxins, drug residues and pesticides are present. Low-cost, rapid screening procedures are sought to discriminate the suspect samples from the population, thus selecting only these to be forwarded for confirmatory analysis. Many biosensor assays have been developed as screening tools in food contaminant analysis, but these tend to be electrochemical, fluorescence or surface plasmon resonance based. An alternative approach is the use of biolayer interferometry, which has become established in drug discovery and life science studies but is only now emerging as a potential tool in the analysis of food contaminants. A biolayer interferometry biosensor was assessed using domoic acid as a model compound. Instrument repeatability was tested by simultaneously producing six calibration curves showing replicate repeatability (n = 2) ranging from 0.1 to 6.5 % CV with individual concentration measurements (n = 12) ranging from 4.3 to 9.3 % CV, giving a calibration curve midpoint of 7.5 ng/ml (2.3 % CV (n = 6)). Reproducibility was assessed by producing three calibration curves on different days, giving a midpoint of 7.5 ng/ml (3.4 %CV (n = 3)). It was further shown, using assay development techniques, that the calibration curve midpoint could be adjusted from 10.4 to 1.9 ng/ml by varying assay parameters before the simultaneous construction of three calibration curves in matrix and buffer. Sensitivity of the assay compared favourably with previously published biosensor data for domoic acid. © 2013 Springer-Verlag Berlin Heidelberg.

Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs

We describe formulation and evaluation of novel dissolving polymeric microneedle (MN) arrays for the facilitated delivery of low molecular weight, high dose drugs. Ibuprofen sodium was used as the model here and was successfully formulated at approximately 50% w/w in the dry state using the copolymer poly(methylvinylether/maleic acid). These MNs were robust and effectively penetrated skin in vitro, dissolving rapidly to deliver the incorporated drug. The delivery of 1.5mg ibuprofen sodium, the theoretical mass of ibuprofen sodium contained within the dry MN alone, was vastly exceeded, indicating extensive delivery of the drug loaded into the baseplates. Indeed in in vitro transdermal delivery studies, approximately 33mg (90%) of the drug initially loaded into the arrays was delivered over 24h. Iontophoresis produced no meaningful increase in delivery. Biocompatibility studies and in vivo rat skin tolerance experiments raised no concerns. The blood plasma ibuprofen sodium concentrations achieved in rats (263μgml(-1) at the 24h time point) were approximately 20 times greater than the human therapeutic plasma level. By simplistic extrapolation of average weights from rats to humans, a MN patch design of no greater than 10cm(2) could cautiously be estimated to deliver therapeutically-relevant concentrations of ibuprofen sodium in humans. This work, therefore, represents a significant progression in exploitation of MN for successful transdermal delivery of a much wider range of drugs.

Parents' experiences of caring for their infant following surgery in the neonatal period: A literature review

Previous research with parents of preterm and low-birth weight infants admitted to the Neonatal Intensive Care Unit (NICU) has indicated the following: (i) parents are at risk of experiencing stress associated with the NICU environment; (ii) parents are at risk of short- and longer-term psychological distress; and (iii) the family is at risk of longer-term stress and strain. However, parents of infants admitted to the NICU for surgery are an under-researched population. This paper provides an overview of the current literature in relation to this issue. The results highlight the paucity of research conducted with parents of infants admitted to the NICU for surgery. A number of gaps and limitations were also identified in the current literature, including a lack of examination why some parents cope better than others, and a focus solely on parents of preterm and low birth weight infants. To conclude, further research with parents of infants who had surgery in the first few weeks of life is needed. Such information could help inform clinicians caring for these infants and their families, and would enable identification of those parents and families most at risk.

Challenges of minimizing heat loss at birth: A narrative overview of evidence-based thermal care interventions

Evidence-based thermal care recommendations designed to minimize heat loss immediately at birth are readily available however, hypothermia still persists as a global challenge especially when caring for the most immature and smallest preterm infants. In this narrative overview we aim to provide the reader with a succinct summary of the causes and consequences of hypothermia, the extent of the problem (rates of hypothermia), principles of good thermal care, delivery room preventative measures, the research evidence underpinning existing interventions, current issues in practice, and the way forward. Due to the plethora of research literature available in this subject area, our article will focus primarily on evidence derived from systematic reviews and randomized or quasi-randomized controlled trials assessing the effectiveness of interventions to prevent hypothermia in the most vulnerable (preterm/low birth weight) infants where the intervention or combination of interventions is applied immediately at birth. © 2014.

Early pain experience, child and family factors, as precursors of somatization:a prospective study of extremely premature and fullterm children

In a prospective study of 36 children who were extremely low birthweight (ELBW: <1000 g) preterm infants and 36 matched full-term controls, differences were found in somatization at age 4 1/2 years. Only children who had been extremely premature, and thereby experienced prolonged hospitalization and repeated medical intervention in infancy, had clinically high somatization scores on the Personality Inventory for Children. The combination of family relations at age 4 1/2 years, neonatal intensive care experience, poor maternal sensitivity to child cues in mother-child interaction observed at age 3 years, and child avoidance of touch or holding at age 3, predicted somatization scores, prior to school entry. Due to the known higher incidence of actual medical problems among children with a history of extreme prematurity, the high somatization ELBW children were compared with the normal somatization ELBW children. There were no differences in prevalence of actual medical problems between the 2 ELBW groups, and the importance of maternal factors in relation to somatization was confirmed. Child temperament at age 3, but not personality at 4 1/2, was related to somatization. The etiology of recurrent physical complaints of no known medical cause appears to be a multi-dimensional problem. Non-optimal parenting may contribute to the development of inappropriate strategies for coping with common pains of childhood, or of chronic pain patterns, in some children who have experienced prolonged or repeated pain as neonates.

Trends in the prevalence of cerebral palsy in Northern Ireland, 1981-1997

We describe trends in the prevalence of cerebral palsy (CP) by birth weight group, and in the severity of motor impairments and presence of associated intellectual impairment, in Northern Ireland from 1981 to 1997 (n=909; 510 males, 399 females; total population 415 936 live births) using data from a population-based register of CP. Children with suspected CP or who died before 1 year of age and those with CP of postneonatal origin were excluded. Prevalence of CP was 2.2 per 1000 live births without significant change over time. Among very-low-birthweight (<1500g) live births, prevalence was 44.5 per 1000 (95% confidence interval 32.3–59.8) from 1994 to 1997, with evidence of a statistically significant decline in prevalence since the mid- to late 1980s accompanied by a decrease in the severity of motor impairment and likelihood of intellectual impairment. Among moderately-low-birthweight (1500–2499g) children there was weaker evidence of a peak prevalence in the late 1980s. Prevalence among normal-birthweight infants did not change significantly, but outcome in terms of severity of motor impairment and intellectual impairment improved in the 1990s. Occurrence of bilateral spasticity from 1994 to 1997 was associated with greater severity and likelihood of intellectual impairment for normal-birthweight individuals than for low- or very-low-birth weight individuals.

Determination of the molecular weight distribution of non-enzymatic browning products formed by roasting of glucose and glycine and studies on their effects on NADPH-cytochrome c-reductase and glutathione-S-transferase in Caco-2 cells

After thermal treatment of a mixture of glucose and glycine for 2 h at 125 degreesC, about 60% of the starting material was converted into nonsoluble, black pigments, whereas 40% of the mixture was still water-soluble. Dialysis of the latter fraction revealed 30.4% of low molecular weight compounds (LMWs; MW <10 000 De) and 10.0% high-molecular weight products [HMWs; MW greater than or equal to 10000 Dal. The water-soluble Maillard reaction products (MRPs) were separated by gel permeation chromatography and ultrafiltration, revealing that 60% of the water-soluble products of the total carbohydrate/amino acid mixture had MWs <1 000 Da and consisted mainly of non-coloured reaction products. MRPs with MWs between 1000 and 30000 Da were Found in comparatively low yields (about 1.3%). In contrast, about 31.1% of the MRPs exhibited MWs > 30000 Da, amongst which 14.5% showed MWs > 100000 Da, thus indicating an oligomerisation of LMWs to melanoidins under roasting conditions. To investigate the physiological effects of these MRPs, xenobiotic enzyme activities were analysed in intestinal Caco-2 cells. For Phase-I NADPH-cytochrome c-reductase, the activity in the presence of the LMW and HMW fraction was decreased by 13% and 22%: respectively. Phase-II glutathione-S-transferase activity decreased by 15% and 18%, respectively, after incubation with the LMW and the HMW fractions. Considering the different yields, 30% and 10%, respectively, of the LMW and the HMW fractions, the total amount of the LMW fraction present in the glucose-glycine mixture is more active in modulating three enzyme activities than that of the HMW fraction.

Use of a novel micro-fluidic device to create arrays for multiplex analysis of large and small molecular weight compounds by surface plasmon resonance

There is an increasing demand to develop biosensor monitoring devices capable of biomarker profiling for predicting animal adulteration and detecting multiple chemical contaminants or toxins in food produce. Surface plasmon resonance (SPR) biosensors are label free detection systems that monitor the binding of specific biomolecular recognition elements with binding partners. Essential to this technology are the production of biochips where a selected binding partner, antibody, biomarker protein or low molecular weight contaminant, is immobilised. A micro-fluidic immobilisation device allowing the covalent attachment of up to 16 binding partners in a linear array on a single surface has been developed for compatibility with a prototype multiplex SPR analyser.

The immobilisation unit and multiplex SPR analyser were respectively evaluated in their ability to be fit-for-purpose for binding partner attachment and detection of high and low molecular weight molecules. The multiplexing capability of the dual technology was assessed using phycotoxin concentration analysis as a model system. The parent compounds of four toxin groups were immobilised within a single chip format and calibration curves were achieved. The chip design and SPR technology allowed the compartmentalisation of the binding interactions for each toxin group offering the added benefit of being able to distinguish between toxin families and perform concentration analysis. This model is particularly contemporary with the current drive to replace biological methods for phycotoxin screening.

Adiponectin multimers, body weight and markers of cardiovascular risk in adolescence: Northern Ireland Young Hearts Project:Northern Ireland Young Hearts Project

Background:Research examining the relationship between adiponectin (AN) isoforms, body weight and cardiovascular (CV) risk factors is limited, particularly in younger populations. Objectives:To investigate the inter-relationships between AN isoforms and CV risk factors, and their dependence on body weight status, in adolescents. Design:Blood samples from 92 obese, 92 overweight and 92 normal weight age- and sex-matched adolescents were analysed for traditional cardiovascular disease (CVD) risk biomarkers and also total, high molecular weight (HMW), medium and low molecular weight (LMW) AN. Results:A significant inverse association was observed between total and HMW AN and waist-hip ratio (P=0.015, P=0.006, respectively), triglycerides (P=0.003, P=0.003, respectively) and systolic blood pressure (P=0.012, P=0.024, respectively) and a significant positive association with high-density lipoprotein (P<0.001, P<0.001, respectively) in multi-adjusted analyses. There was no evidence of a relationship between multimeric AN and high-sensitivity C-reactive protein. There was also little evidence of a relationship between LMW AN and CVD risk factors. There was a strong, body mass index (BMI)-independent, association between AN, CVD biomarkers and the hypertriglyceridemic waist phenotype. Conclusion:Prominent, BMI-independent associations between total and HMW AN, but not LMW AN, and CVD risk factors were already evident in this young population. This research in adolescents supports the contention that AN subfractions may have different biological actions. These associations in apparently healthy adolescents suggest an important role for AN and its subfractions in the pathogenesis of metabolic syndrome traits and indicate that the potential for total or HMW AN to act as early universal biomarkers of CV risk warrants further study.

Neonatal procedural pain and preterm infant cortisol response to novelty at 8 months

Stress systems may be altered in the long term in preterm infants for multiple reasons, including early exposure to procedural pain in neonatal intensive care. This question has received little attention beyond hospital discharge. Stress responses (cortisol) to visual novelty in preterm infants who were born at extremely low gestational age (ELGA; <or =28 weeks), very low gestational age (VLGA; 29-32 weeks), and term were compared at 8 months of age corrected for prematurity (corrected chronological age [CCA]). In addition, among the preterm infants, we evaluated whether cortisol levels at 8 months were related to neonatal exposure to procedural pain and morphine in the neonatal intensive care unit.

Extremely premature (<or = 800 g) schoolchildren:multiple areas of hidden disability

To examine the functional abilities of extremely low birthweight (ELBW, <or = 800 g) children at school age compared with full term children.

Detection of Low-Concentration Contaminants in Solution by Exploiting Chemical Derivatization in Surface-Enhanced Raman Spectroscopy