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Vitamin D intakes are concerningly low. Food-based strategies are urgently warranted to increase vitamin D intakes and subsequently improve 25-hydroxyvitamin D (25(OH)D) concentrations. This acute randomised three-way crossover study investigated the efficacy of vitamin D biofortified pork derived from pigs exposed to UVB light to increase serum 25(OH)D3 concentrations, compared to a dose-matched vitamin D3 supplement and control pork in adults (n = 14). Blood samples were obtained at baseline and then 1.5, 3, 6, 9 and 24 h postprandially. There was a significant effect of time (p < 0.01) and a significant treatment*time interaction (p < 0.05). UV pork and supplement significantly increased within-group serum 25(OH)D3 concentrations over timepoints (p < 0.05) (max. change 0.9 nmol/L (2.2%) UV pork, 1.5 nmol/L (3.5%) supplement, 0.7 nmol/L (1.9%) control). Vitamin D biofortified pork modestly increased 25(OH)D3 concentrations and produced a similar response pattern as a dose-matched vitamin D supplement, but biofortification protocols should be further optimised to ensure differentiation from standard pork.

The ensuing ischemia due to the disruption of blood supply to the brain is one of the most common causes of stroke. Evidence suggests a clear association of the ischemic injury with vascular dementia and Alzheimer's disease (AD). In response to the brain ischemia, a cascade reaction starts leading to neuronal damage due to oxidative stress and other inflammatory mediators. A pilot study was done, which showed that following stroke, monomeric-C-reactive protein (mCRP) is expressed in large quantities around the infarcted zone and this CRP is able to induce neurodegeneration and inflammation potentially perpetuating dementia.We examined both patient brain samples and excised mouse brain tissue, previously injected with 1.75 mg/mL mCRP into the CA1 area of the hippocampus through the stereotactic surgical procedures and followed them over a period of over 6 months. The distribution of mCRP was examined through immunohistochemistry (mouse anti-human mCRP-specific antibodies 8C10).We observed a novel finding: those micro vessels close to the injection location were strongly stained with mCRP only in the mice that had been injected with mCRP, indicating that this small blood vessel can spread it throughout the brain.mCRP found in the brain after a hemorrhagic stroke promotes damage over a large area via the induction of inflammation and degeneration of perivascular compartments.

Purpose To determine the small intestinal concentration of endocannabinoids (ECs), N-acylethanolamines (NAEs) and their precursors N-acylphosphatidylethanolamines (NAPEs) in humans. To identify relationships between those concentrations and habitual diet composition as well as individual inflammatory status. Methods An observational study was performed involving 35 participants with an ileostomy (18W/17M, aged 18–70 years, BMI 17–40 kg/m2). Overnight fasting samples of ileal fluid and plasma were collected and ECs, NAEs and NAPEs concentrations were determined by LC-HRMS. Dietary data were estimated from self-reported 4-day food diaries. Results Regarding ECs, N-arachidonoylethanolamide (AEA) was not detected in ileal fluids while 2-arachidonoylglycerol (2-AG) was identified in samples from two participants with a maximum concentration of 129.3 µg/mL. In contrast, mean plasma concentration of AEA was 2.1 ± 0.06 ng/mL and 2-AG was 4.9 ± 1.05 ng/mL. NAEs concentrations were in the range 0.72–17.6 µg/mL in ileal fluids and 0.014–0.039 µg/mL in plasma. NAPEs concentrations were in the range 0.3–71.5 µg/mL in ileal fluids and 0.19–1.24 µg/mL in plasma being more abundant in participants with obesity than normal weight and overweight. Significant correlations between the concentrations of AEA, OEA and LEA in biological fluids with habitual energy or fat intakes were identified. Plasma PEA positively correlated with serum C-reactive protein. Conclusion We quantified ECs, NAEs and NAPEs in the intestinal lumen. Fat and energy intake may influence plasma and intestinal concentrations of these compounds. The luminal concentrations reported would allow modulation of the homeostatic control of food intake via activation of GPR119 receptors located on the gastro-intestinal mucosa. Clinical trial registry number and website NCT04143139; www.clinicaltrials.gov.

The pathogenesis of immune checkpoint inhibitor (ICI)-colitis remains incompletely understood. We sought to identify key cellular drivers of ICI-colitis and their similarities to idiopathic ulcerative colitis, and to determine potential novel therapeutic targets.We used a cross-sectional approach to study patients with ICI-colitis, those receiving ICI without the development of colitis, idiopathic ulcerative colitis, and healthy controls. A subset of patients with ICI-colitis were studied longitudinally. We applied a range of methods, including multiparameter and spectral flow cytometry, spectral immunofluorescence microscopy, targeted gene panels, and bulk and single-cell RNA sequencing.We demonstrate CD8Interferon gamma-producing CD8

Objective: Dietary soy may improve menopausal symptoms, and subsequently mediate mood. This novel study examines various doses of dietary soy drink on everyday mood stability and variability in postmenopausal women. Methods: Community-dwelling women (n = 101), within 7 years postmenopause, consumed daily either a low (10 mg, n = 35), medium (35 mg, n = 37), or high (60 mg, n = 29) dose of isoflavones, for 12 weeks. Menopausal symptoms and repeated measures of everyday mood (positive [PA] and negative [NA] affect) (assessed at four time points per day for 4 consecutive days, using The Positive and Negative Affect Schedule) were completed at baseline and follow-up. Results: The dietary soy intervention had no effect on everyday mood stability (for PA [F{2,70} = 0.95, P = 0.390] and NA [F{2,70} = 0.72, P = 0.489]) or variability (for PA [F{2,70} = 0.21, P = 0.807] and for NA [F{2,70} = 0.15, P = 0.864]), or on menopausal symptoms (for vasomotor [F{2,89} = 2.83, P = 0.064], psychological [F{2,88} = 0.63, P = 0.535], somatic [F{2,89} = 0.32, P = 0.729], and total menopausal symptoms [F{2,86} = 0.79, P = 0.458]). There were between-group differences with the medium dose reporting higher PA (low, mean 24.2, SD 6; and medium, mean 29.7, SD 6) and the low dose reporting higher NA (P = 0. 048) (low, mean 11.6, SD 2; and high, mean 10.6, SD 1) in mood scores. Psychological (baseline M = 18 and follow-up M = 16.5) and vasomotor (baseline M = 4.2 and follow-up M = 3.6) scores declined from baseline to follow-up for the overall sample. Conclusions: Soy isoflavones had no effect on mood at any of the doses tested. Future research should focus on the menopause transition from peri to postmenopause as there may be a window of vulnerability, with fluctuating hormones and increased symptoms which may affect mood.

Structured diabetes education (SDE) is an evidence-based intervention that supports self-management in people with type 2 diabetes. In the United Kingdom, health care providers working in primary care settings are responsible for referring people with type 2 diabetes to SDE programs. However, national audits record a high percentage of nonattenders. We explored the personal experience of living with type 2 diabetes that led to individuals declining invitations to attend SDE programs. The themes suggested that emotional, cognitive, and social issues related to diagnosis and living with diabetes may be responsible for declining to attend SDE and that these factors may be masked by explanations of practical barriers. A person-centered approach to understanding the personal meaning of being diagnosed and living with type 2 diabetes may help to identify individuals’ psychosocial barriers to attending SDE.

Introduction Is Therapeutic Listening effective for children born preterm presenting with sensory dysregulation, attention and cognitive problems? Methods 22 children (BW1500g) 3-4 years were enrolled in a single centre, prospective, assessor-blinded RTC. Outcome measures: Winnie-Dunn Sensory Profile; Peabody Developmental Motor Scales; Reynell Attention Scale; Preschool Language Scales - 3; RAPT; WPPSI - IV; Parent Review Questionnaires. Results The intervention group (n=9) showed better improvement in sensory processing, compared to controls (n=9) (6.4 fold improvement in sensation seeking; 5.0 in auditory processing; 4.0 in tactile processing). Six intervention children (67%) improved in vestibular processing. Attention levels improved for 9 (100%) children in the intervention group and for 7 (78%) in the control group. Higher level domains (Peabody motor skills, Auditory Comprehension, Expressive Communication, RAPT scale, and WPPSI scores) showed mixed results. Parents reported positive changes in their child's development. Conclusion Therapeutic Listening (TL) is a feasible intervention for preterm children to improve attention levels and sensory processing skills.

Purpose: Cognitive decline is commonly reported during the menopausal transition, with memory and attention being particularly affected. The aim of this study was to investigate the effects of a commercially available soy drink on cognitive function and menopausal symptoms in post-menopausal women. Methods: 101 post-menopausal women, aged 44–63 years, were randomly assigned to consume a volume of soy drink providing a low (10 mg/day; control group), medium (35 mg/day), or high (60 mg/day) dose of isoflavones for 12 weeks. Cognitive function (spatial working memory, spatial span, pattern recognition memory, 5-choice reaction time, and match to sample visual search) was assessed using CANTAB pre- and post-the 12 week intervention. Menopausal symptoms were assessed using Greene’s Climacteric Scale. Results: No significant differences were observed between the groups for any of the cognitive function outcomes measured. Soy drink consumption had no effect on menopausal symptoms overall; however, when women were stratified according to the severity of vasomotor symptoms (VMS) at baseline, women with more severe symptoms at baseline in the medium group had a significant reduction (P = 0.001) in VMS post-intervention (mean change from baseline score: − 2.15 ± 1.73) in comparison to those with less severe VMS (mean change from baseline score: 0.06 ± 1.21). Conclusions: Soy drink consumption had no effect on cognitive function in post-menopausal women. Consumption of ~ 350 ml/day (35 mg IFs) for 12 weeks significantly reduced VMS in those with more severe symptoms at baseline. This finding is clinically relevant as soy drinks may provide an alternative, natural, treatment for alleviating VMS, highly prevalent among western women.

BackgroundLateral ankle sprain is one of the most common musculoskeletal injuries, particularly among the sporting population. Due to such prevalence, many interventions have been tried to prevent initial, or further, ankle sprains. Current research shows that the use of traditional athletic tape can reduce the incidence of sprain recurrence, but this may be at a cost to athletic performance through restriction of motion. Kinesiology tape, which has become increasingly popular, is elastic in nature, and it is proposed by the manufacturers that it can correct ligament damage. Kinesiology tape, therefore, may be able to improve stability and reduce ankle sprain occurrence while overcoming the problems of traditional tape.AimTo assess the effect of kinesiology tape on ankle stability.Methods27 healthy individuals were recruited, and electromyography (EMG) measurements were recorded from the peroneus longus and tibialis anterior muscles. Recordings were taken from the muscles of the dominant leg during induced sudden ankle inversion perturbations using a custom-made tilting platform system. This was performed with and without using kinesiology tape and shoes, creating four different test conditions: barefoot(without tape), shoe(without tape), barefoot(with tape) and shoe(with tape). For each test condition, the peak muscle activity, average muscle activity and the muscle latency were calculated.ResultsNo significant difference (p>0.05) was found by using the kinesiology tape on any of the measured variables while the wearing of shoes significantly increased all the variables.ConclusionKinesiology tape has no effect on ankle stability and is unable to nullify the detrimental effects that shoes appear to have.

The endocannabinoid system is a lipid signalling system with several regulatory functions throughout the body including regulation of appetite, food intake, macronutrient metabolism, pain sensation, blood pressure, mood, cognition and immunity. It consists of endocannabinoids (ECs), their receptors and enzymes involved in their synthesis and degradation. The two best-characterized endocannabinoids are N-arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). They are ligands of cannabinoid receptors CB1 and CB2 which are located in the central nervous system (CNS) but also in in the enteric nervous system, in the liver and in the adipose tissue.Several structural congeners of ECs including N-acylethanolamines (NAEs) such as oleoylethanolamine (OEA), linoleyethanolamine (LEA), and palmitoyletahanolamine (PEA), show similar mechanisms of action, tissue distribution as well as pathways of formation and breakdown. They are considered “endocannabinoid-like” molecules acting through receptors that are located both in CNS and in the gastro-intestinal tract mucosa such as the G-protein coupled receptor 119 (GPR119) and peroxisome proliferator-activated receptors (PPARs). NAEs display EC50 values for human GPR119 and PPAR-α between 65 ng/mL and 1000 ng/mL. Some evidence indicated that NAEs, their phosphorylated precursors N-acylphosphatidylethanolamines (NAPEs) and ECs are also present in food. Thus, we developed a food database of these molecules and we calculated the daily dietary intake in a healthy population.This study aimed to evaluate whether the concentrations of NAPEs, NAEs and ECs in the human intestinal lumen may support their activity through the receptors lining in the gastro-intestinal tract and if they correlated with those in plasma.The observational study (16/NI/0267, Ulster University) involved 35 ileostomists (18F/17M, aged 18–70 y, BMI 17–40 kg/m2) who collected overnight fasting samples of ileal fluid and plasma. The concentrations of NAEs, NAPEs and ECs in biological samples were determined by LC-HRMS.Data showed that NAEs and NAPEs were present in ileal fluids and plasma from all subjects ranging between 46851.0–104742.8 ng/mL and 0.3–59.6 ng/mL in ileal samples and 1159.4–3985.7 ng/mL and 0.19–1.24 ng/mL in plasma, respectively. Contrarily, no ECs in ileal fluids were found except 2-AG in two ileal samples whereas they ranged between 1.6–22.3 ng/mL in plasma. Differences between genders and associations of plasma levels with individual energy intakes were found.Altogether, the data demonstrated that NAEs in the intestinal lumen are sufficient to elicit metabolic responses through the gastro-intestinal receptors.

Evidence from observational studies indicates that seaweed consumption may reduce the risk of non-communicable diseases such as cardiovascular disease, type two diabetes, and obesity. Accumulating evidence from in vitro and animal studies suggest seaweed have antihyperlipidemic, anti-inflammatory and antioxidant properties which may in part be attributed to the high content of soluble dietary fibre in seaweeds. The viscosity of seaweed fibres is suggested to mediate antihyperlipdiemic effects via the alteration of lipid/bile acid absorption kinetics to decrease low-density lipoprotein cholesterol (LDL). Thus, there is a need to evaluate the efficacy of seaweed derived dietary fibre in the management of dyslipidemia. Therefore, the aim of this study was to determine the effect of a fibre rich extract from Palmaria palmata on the lipid profile as well as markers of inflammation and oxidative stress in healthy adults. A total of 60 healthy participants (30 male and 30 female) aged 20 to 58 years, were assigned to consume the Palmaria palmata fibre extract (5g/day), Synergy-1 and the placebo (maltodextrin) for a duration of 4 weeks with a minimum 4 week washout between each treatment in a double blind, randomised crossover study conducted over 5 months. Fasting concentrations of cholesterol, triglycerides and high-density lipoprotein cholesterol (HDL) were analysed and low-density lipoprotein cholesterol (LDL) and LDL: HDL ratio was calculated. C-reactive protein (CRP) and Ferric Reducing Ability of Plasma (FRAP) were analysed as markers of inflammation and oxidative stress, respectively. Supplementation for 4 weeks with Palmaria palmata resulted in favourable changes to lipid profiles with a reduced LDL:HDL ratio; however intention-to-treat univariate ANCOVA identified no significant difference between the treatment groups over time on any of the lipid profile markers. A non-significant increase in CRP and triglyceride concentration along with lower FRAP was also observed with Palmaria palmata supplementation. Evidence from this study suggests that Palmaria palmata may have effects on lipid metabolism and appears to mobilise triglycerides. More research is needed in individuals with dyslipidaemia to fully elucidate these effects.

Age-related bone loss leads to a significant decline in bone formation and an increase in bone resorption resulting in a marked negative effect on bone mineral density (BMD). This bone turnover cycle can be further disrupted by estrogen deficiency during menopause which can lead to a great net loss of bone in post-menopausal women. Evidence suggests that n-3 polyunsaturated fatty acids (PUFA) may have a beneficial effect on the inflammatory regulation of bone remodelling and thus reducing bone loss. This study investigated the relationship between PUFA status, total body bone mineral density (BMD) and bone turnover markers in a cohort of post-menopausal women in Northern Ireland. Total body T-score and BMD were measured using dual energy x-ray absorptiometry (DEXA) in 300 non-osteoporotic post-menopausal women (45–75 years). The bone turnover markers serum osteocalcin, alkaline phosphatase, C-terminal telopeptides of type 1 collagen (CTX) and urinary deoxypyridinoline (DPD) were quantified. Total n6 PUFA (LA + AA) and n3 PUFA (ALA + EPA + DPA + DHA) were measured in serum using gas chromatography mass spectrometry. Total n3:n6 ratio was calculated. Dietary intake and lifestyle factors were determined by 4 day food diary and questionnaire, respectively. Spearman rank correlation analysis were conducted to investigate the relationship between PUFA and total body BMD. Secondary analysis investigated the relationship between PUFA and the bone turnover markers. Median (IQR) age was 61 (10) years, body mass index 27 (6) kg/m2, total body BMD, 1.3 (0.11) g/cm2 and age at menopause was 50 (6) years. Total median (IQR) serum n-3 PUFA status was 0.231 (0.128) mg/mL, total n6 PUFA was 1.248 (0.477) mg/mL and the n6:n3 PUFA ratio was 5.82 (2.63). Median (IQR) daily fish consumption was 25 (46) grams, calcium 702 (364) mg and vitamin D 2.21 (2.3) μg. There was no significant correlation between markers of total n3, n6, n6:n3 ratio and total body T-score, BMD or bone mineral content. PUFA was not significantly associated with total body BMD. There was a significant negative correlation between the urinary bone resorption marker DPD and total n3 PUFA (r = -0.137, P = 0018); EPA (r = -0.150, P = 0.009), and DPA (r = -0.118, P = 0.042). A significant negative correlation was observed between urinary CTX and the n-6 PUFA AA (r = -0.121, P = 0.036), the n3 PUFA ALA (r = -0.123, P = 0.033). PUFA were associated with less bone resorption therefore it is plausible that PUFA have a positive anti-inflammatory effect on bone resorption and warrants further investigation.

Aim To explore the organizational context in which Type 2 diabetes structured group education is provided. Methods Four Clinical Commissioning Groups in England providing Type 2 diabetes structured self-management education participated in a qualitative study exploring the context for provision of that education. Using UK National Diabetes Audit returns, two Clinical Commissioning Groups were selected that had non-attendance rates of ≤25%, and two that had non-attendance rates of ≥50%. Between May 2016 and August 2017, 20 interviews were conducted with Clinical Commissioning Group staff including: commissioners, healthcare professionals, managers, general practitioners and diabetes educators. Data gathering was prolonged as it proved challenging to engage with healthcare staff as a result of frequent local restructuring and service disruption. Results Local audits revealed discrepancies in basic data such as referral and attendance numbers compared with national audit data. There was a commonality in the themes identified from interviews: diabetes education was rarely embedded in service structure; where education uptake was poor, a lack of central support to delivery teams was noticeable; and where education uptake was positive, delivery teams were actively engaged, sometimes relying on enthusiastic individuals. Both situations put the local sustainability of diabetes education at risk. Conclusions There appears to be a link between attendance rates and organizational issues, therefore, when considering how to increase attendance rates, the state of the diabetes education infrastructure should be reviewed. Good uptake of diabetes education can be too reliant on the enthusiastic commitment of small teams or individuals delivering the education.

peer-reviewed The full text of this article will not be available in ULIR until the embargo expires on the 06/09/2019 no abstract available

Human blood monocytes are subclassified as classical, intermediate and nonclassical. In this study, it was shown that conventionally defined human intermediate monocytes can be divided into two distinct subpopulations with mid- and high-level surface expression of HLA-DR (referred to as DRmid and DRhi intermediate monocytes). These IM subpopulations were phenotypically and functionally characterized in healthy adult blood by flow cytometry, migration assays and lipoprotein uptake assays. Their absolute numbers and proportions were then compared in blood samples from obese and nonobese adults. DRmid and DRhi intermediate monocytes differentially expressed several proteins including CD62L, CD11a, CX3CR1 and CCR2. Overall, the DRmid intermediate monocytes surface profile more closely resembled that of classical monocytes while DRhi intermediate monocytes were more similar to nonclassical. However, in contrast to classical monocytes, DRmid intermediate monocytes migrated weakly to CCL2, had reduced intracellular calcium flux following CCR2 ligation and favored adherence to TNF alpha-activated endothelium over transmigration. In lipid uptake assays, DRmid intermediate monocytes demonstrated greater internalization of oxidized and acetylated low-density lipoprotein than DRhi intermediate monocytes. In obese compared to nonobese adults, proportions and absolute numbers of DRmid, but not DRhi intermediate monocytes, were increased in blood. The results are consistent with phenotypic and functional heterogeneity within the intermediate monocytes subset that may be of specific relevance to lipoprotein scavenging and metabolic health. The authors acknowledge the kind contribution of time and samples by study participants, as well as the assistance of the nursing and medical staff at the Centre for Diabetes, Endocrinology and Metabolism (CDEM) at Galway University Hospital. We also acknowledge assistance provided by Dr Paula O'Shea, Consultant Biochemist and staff at the Department of Biochemistry, Galway University Hospital. EPC, SN and SMS were supported by the Molecular Medicine Ireland Clinical and Translational Research Scholars Programme which was funded by the Irish Government's Programme for Research in Third Level Institutions, Cycle 5 and by NUI Galway. MCD was supported by the Health Services Executive (HSE) of Ireland, Medical Education, Training & Research (METR) Section and the Health Research Board (HRB) of Ireland under the National Specialist Registrar/Senior Registrar Academic Fellowship Program (NSAFP). JKE was partly‐funded by grants from the Irish Research Council for Science, Engineering and Technology (IRCSET EMPOWER fellowship) and the Health Research Board (grant number RP2006182N). Funding support was also received from Science Foundation Ireland [Regenerative Medicine Institute Strategic Research Cluster, grant number 09/SRC‐B1794; CÚRAM Research Centre, grant number 13/RC/2073 (MDG, TO'B, RC) and Principal Investigators grant numbers 07/IN1/B958 and 13/IA/1954 (NFL)], from the European Commission [Horizon 2020 Collaborative Health Project NEPHSTROM (Novel Stromal Cell Therapy for Diabetic Kidney Disease; grant 634086 (MDG, TO'B)] and from the European Regional Development Fund (all authors). All flow cytometry and cell sorting experiments were performed in the NUI Galway Flow Cytometry Core Facility which is supported by funds from NUI Galway, Science Foundation Ireland, the Irish Government's Programme for Research in Third Level Institutions, Cycle 5 and the European Regional Development Fund. peer-reviewed

Body fat distribution has been shown to be a predictor of adhesion molecule and inflammatory marker expression albeit the effect of modest weight change on concentrations of adhesion molecules and inflammatory markers in postmenopausal women are not fully understood. The primary aim was to investigate the effects of weight change on adhesion molecules and inflammatory markers over 24 months in postmenopausal women. Body composition was assessed in 254 healthy postmenopausal women using dual-energy X-ray absorptiometry (DXA). Adhesion molecules and inflammatory markers were analysed by multiplex ELISA. Participants weight gain/loss at 24 months was defined as any value that was either above/below the weight value recorded at baseline. Postmenopausal women with an average weight loss of 3% had significantly decreased leptin concentrations by 18% at 24 months (P

This 24-mo randomized, double-blind, controlled trial aimed to examine whether supplementation with a natural marine-derived multi-mineral supplement rich in calcium (Ca) taken alone and in conjunction with short-chain fructo-oligosaccharide (scFOSs) has a beneficial effect on bone mineral density (BMD) and bone turnover markers (BTMs) in postmenopausal women. A total of 300 non-osteoporotic postmenopausal women were randomly assigned to daily supplements of 800 mg of Ca, 800 mg of Ca with 3.6 g of scFOS (CaFOS), or 9 g of maltodextrin. BMD was measured before and after intervention along with BTMs, which were also measured at 12 mo. Intention-to-treat ANCOVA identified that the change in BMD in the Ca and CaFOS groups did not differ from that in the maltodextrin group. Secondary analysis of changes to BTMs over time identified a greater decline in osteocalcin and C-telopeptide of type I collagen (CTX) in the Ca group compared with the maltodextrin group at 12 mo. A greater decline in CTX was observed at 12 mo and a greater decline in osteocalcin was observed at 24 mo in the CaFOS group compared with the maltodextrin group. In exploratory subanalyses of each treatment group against the maltodextrin group, women classified with osteopenia and taking CaFOS had a smaller decline in total-body (P = 0.03) and spinal (P = 0.03) BMD compared with the maltodextrin group, although this effect was restricted to those with higher total-body and mean spinal BMD at baseline, respectively. Although the change in BMD observed did not differ between the groups, the greater decline in BTMs in the Ca and CaFOS groups compared with the maltodextrin group suggests a more favorable bone health profile after supplementation with Ca and CaFOS. Supplementation with CaFOS slowed the rate of total-body and spinal bone loss in postmenopausal women with osteopenia-an effect that warrants additional investigation. This trial was registered at www.controlled-trials.com as ISRCTN63118444.

To examine the effects of different torsional flexibilities of shoes on gait and stability in children who are newly walking.Twenty-five children walking 5 months or less were evaluated barefoot and in 4 shoes with different torsional flexibilities (UltraFlex, MidFlex, LowFlex, and Stiff). Gait pattern was assessed using GaitMatII. Stability was determined by the number of stumbles/falls during functional tasks.Stance time was shorter barefoot compared with all shoe conditions (P = .000). Stance time was shorter in UltraFlex than in LowFlex (P = .000). Step width was wider in UltraFlex than in MidFlex and LowFlex (P = .028). Velocity, step length, and the number of stumbles/falls did not differ significantly across shoe conditions. Children walking for 2 months or less had significantly more stumbles and falls than children walking more than 2 months (P = .003).Stance time and step width differ across shoe conditions. Stability does not differ across shoe conditions.

Background:In a previous pilot study of “cruisers” (nonindependent ambulation), “early walkers” (independent ambulation for 0–5 months), and “experienced walkers” (independent ambulation for 6–12 months), developmental age significantly affected the children’s stability when walking and performing functional activities. We sought to examine how shoe structural characteristics affect plantar pressure distribution in early walkers.Methods:Torsional flexibility was evaluated in four shoe designs (UltraFlex, MedFlex, LowFlex, and Stiff based on decreasing relative flexibility) with a structural testing machine. Plantar pressures were recorded in 25 early walkers while barefoot and shod at self-selected walking speeds. Peak pressure was calculated over ten masked regions for the barefoot and shod conditions.Results:Torsional flexibility, the angular rotation divided by the applied moment about the long axis of the shoe, was different across the four shoe designs. As expected, UltraFlex was the most flexible and Stiff was the least flexible. As applied moment increased, torsional flexibility decreased in all footwear. When evaluating early walkers during gait, peak pressure was significantly different across shoe conditions for all of the masked regions. The stiffest shoe had the lowest peak pressures and the most flexible shoe had the highest.Conclusions:It is likely that increased shoe flexibility promoted greater plantar loading. Plantar pressures while wearing the most flexible shoe are similar to those while barefoot. This mechanical feedback may enhance proprioception, which is a desirable attribute for children learning to walk. (J Am Podiatr Med Assoc 103(4): 297–305, 2013)

Background Infliximab (IFX), an anti-tumour necrosis factor alpha (TNFα) monoclonal antibody, provides clinical benefits in treating Crohn's disease (CD) but its mechanisms of action are not fully elucidated. This study investigated blood monocyte repertoires and the acute effects of IFX infusion on monocyte subset phenotype and function in IFX-treated patients with CD. Methods Monocytes and monocyte subsets were enumerated and phenotypically characterized by multicolor flow cytometry in freshly isolated blood from healthy controls (n = 21) and patients with CD treated with (IFX, n = 24) and without (non-IFX, n = 20) IFX. For the IFX-CD group, blood was sampled immediately before (tough-IFX) and after (peak-IFX) infusion. Monocyte responses to lipopolysaccharide were analyzed by whole-blood intracellular cytokine staining. Results Non-IFX and IFX-CD patients had increased numbers of intermediate (CD14CD16) monocytes compared with healthy controls, whereas classical (CD14CD16) and nonclassical (CD14CD16) monocytes were numerically reduced in the IFX-CD group alone. In all groups, monocyte subsets expressed high surface levels of transmembrane (tm)TNFα. After IFX infusion, a significant reduction in monocyte numbers occurred. Post-IFX monocytopenia was proportionately greatest for classical and intermediate subsets, correlated with postinfusion IFX levels and was not associated with monocyte apoptosis. In contrast, lipopolysaccharide-induced production of TNFα and IL-12 by monocytes was significantly reduced in peak-IFX compared with trough-IFX blood samples. Conclusions Actively managed CD is associated with monocyte repertoire skewing suggestive of chronic inflammatory stimulation. Infused IFX acutely targets monocytes, likely by binding to tmTNFα, resulting in a non-apoptosis-related decline in circulating monocyte numbers and blunting of the inflammatory response of monocytes remaining in the blood.

Objective: Native C-reactive protein (nCRP) is a soluble acute phase reactant whose expression in the vascular wall; in particular, in reactive plaque regions, and circulating levels increase in patients with inflammatory disease. We have recently demonstrated a specific role for the insoluble, monomeric form of CRP (mCRP) in direct stimulation of an- giogenesis and therefore decided to investigate its expression in carotid adventitial vasa vasorum and plaque intimal neovessels to determine if it could be involved in the development of unstable plaque lesions. Methods: We have used immunohistochemistry to examine the expression of both mCRP and nCRP in a series of carotid arterial plaques obtained at transplant (n=20) and employed double immunoflourescent labelling to identify any associa- tion of CRP with active-CD105-positive microvessels. Results: Using characterised and specific antibodies we have identified strong expression of mCRP in adventitial vasa vasorum and angiogenic neovessels from unstable regions of complicated carotid plaques. mCRP was also found to be as- sociated with infiltrating macrophages in inflammatory regions but infrequently with vascular smooth muscle cells. nCRP was expressed much more weakly and only in some regions rich in inflammatory cells. Many of the mCRP-positive ves- sels also stained positive for CD105 suggesting they were actively involved in the process of angiogenesis. Conclusions: Based on our previously published observations of the highly angiogenic nature of mCRP in vitro, we hy- pothesise that mCRP is intimately involved in promotion of neovascularization and possibly, subsequent destabilization of atherosclerotic plaques and could be considered as a possible target for therapeutic manipulation of angiogenesis.

Recent literature suggests that Ca supplements have adverse effects on cardiovascular health. The effects of a Ca-rich supplement administered alone or in combination with short-chain fructo-oligosaccharides (scFOS) on serum lipids in postmenopausal women were examined using secondary data from a 24-month double-blind randomised controlled study. A total of 300 postmenopausal women were randomly assigned to daily supplements of 800 mg of Ca (2·4 g Aquamin) (Ca), 800 mg of Ca with 3 g of scFOS (CaFOS) or control (maltodextrin) (MD). A full lipid profile, body composition, blood pressure and a range of cytokines were measured at baseline and after 24 months. Intention-to-treat ANCOVA assessed treatment effects between the groups. A significant time-by-treatment effect was observed for LDL and total cholesterol for the Ca and CaFOS groups, with both groups having lower LDL and total cholesterol concentrations compared with MD after 24 months. The control group had mean (5·2 mmol/l) total cholesterol concentrations above the normal range (≤5 mmol/l) at 24 months, whereas values remained within the normal range in the treatment groups. There was no significant treatment effect on HDL-cholesterol, TAG, body composition, blood pressure or cytokine concentrations at 24 months, with the exception of IL-4, where there was a significant increase in the CaFOS group compared with the placebo. This study demonstrates a lipid-lowering effect of both the Ca-rich supplement alone and the supplement with scFOS. At the 4-year follow-up, there was no significant difference between the groups for reported diagnosed cardiovascular conditions.

Tumor necrosis factor alpha (TNF-α) has been widely accepted as a therapeutic target for inflammatory disorders including inflammatory bowel disease. Anti-TNF-α monoclonal antibodies (mAbs) including infliximab, adalimumab, golimumab, and certolizumab pegol have revolutionized therapy for these chronic inflammatory disorders. These agents are potent inhibitors of TNF-α, but significant evidence points to the fact that their actions extend beyond simple neutralization of the cytokine. Recent advances in understanding the mechanism of action of anti-TNF-α mAbs has discovered a number of previously unrecognized actions that are likely to be relevant in mediating their anti-inflammatory effects. Many of those actions are mediated by the binding of the antibodies to transmembrane TNF-α (tmTNF-α) and involve complex interactions with other molecular factors and cells. In this review, we have highlighted new information on the mechanism of actions of anti-TNF-α mAbs, from in vitro and in vivo studies. Despite obvious benefits in many patients, the clinical use of these antibodies are hampered by the fact that some patients do not respond to them, and among patients who do respond, many will develop recurrent disease despite continued dosing. Although pharmacokinetic factors explain some of the observed cases of partial or complete resistance to the effects of anti-TNF-α mAbs, other nonresponder patients may be resistant to those agents mechanism of action. A more thorough understanding of the mechanism of action of anti-TNF-α mAbs may allow the development of strategies to individualize therapy and to overcome resistance.

Objective To investigate the indications for and anticipated difficulty of third molar surgery between two different referral settings. Design A prospective study involving completion of a proforma pre- and post-operatively. Setting A dental teaching hospital and a specialist surgical dentistry practice in 2003. Subjects and methods Patients referred for the assessment of their third molars were recruited. Details of the clinical and radiographical assessment for each patient were recorded pre-operatively and the extent of surgery required post-operatively. Results The main indication for referral for third molar extraction was pericoronitis in both centres. A larger number of patients were assessed and treated in a shorter period of time at the surgical dentist compared with the dental hospital. The surgical dentist was accurate in his assessment of the difficulty of surgery 96% of the time compared with 66% for the dental hospital staff. Conclusions This study highlights the benefits for patients in being treated by a surgical dentist. As dental students require exposure to surgical dentistry in order to attain a level of competence, a reduction in the number of patients being referred to dental hospitals may impact upon students' ability to both assess and perform surgical procedures. This may mean that undergraduates will be less able to fulfil the recommendations of the General Dental Council.1 An outreach programme for final year dental students to surgical dentistry practices would benefit all concerned.

Background Clinical trials of anti-tumour necrosis factor alpha (TNF) have shown efficacy in 60–70% of rheumatoid arthritis patients (RA). Predicting response to anti-TNF drugs at baseline remains an elusive goal in RA management. The purpose of this study was to determine if baseline levels of circulating cytokines, soluble receptors, adhesion molecules and metabolic factors differentiate future responders. Methods RA patients (n=29) with active disease were recruited, who had failed on disease modifying drugs and were recommended for anti-TNF treatment. Peripheral blood samples were collected at baseline. Responders were identified by a ≥1.2 reduction in disease activity score (DAS28-ESR) at 6 months. Five protein arrays quantified 33 proteins in pre-treatment plasma (Cytokine I, III and IV; Metabolic I; Adhesion molecule; Randox Laboratories Ltd., UK). Data was analysed by Pearson ranked correlation and logistic regression to clinical measures of disease activity at baseline and six months anti-TNF treatment. Results Elevated levels of interleukin 8 (p=0.043), monocyte chemoattractant protein (p=0.027), granulocyte-macrophage colony-stimulating factor (p=0.020) and soluble interleukin 2α receptor (p=0.01) were associated with high TJC at baseline. No significant relationship with the protein array panels was recorded relative to baseline DAS28-ESR. Significant inverse correlations were observed between absolute change in DAS28-ESR after 6 months of anti-TNF therapy and baseline levels of interleukin 6 (p=0.026) and resistin (p=0.044). Conclusions These findings suggest that baseline levels of specific circulating proteins may help to differentiate RA patient responders to anti-TNF therapies.

The Bayley scale of infant development is employed as the performance indicator at 2 years corrected gestational age for high risk paediatric groups. We compare neurodevelopmental outcomes in two cohorts of VLBW infants born in 1999 to a cohort born a decade later, while also examining the challenges of direct comparison of modified scales: BSID-II (2nd edition of the scales) with Bayley-III, BSID-II was used in the 1999 group and Bayley-III for the 2009 cohort. We demonstrated that over a ten year period there was an improvement in neurodevelopmental scores achieved in VLBW babies. Overall there was almost an 8 point increase in the cognitive scores from the 2009 cohort compared with the 1999 cohort in this time period. The mean motor score increased by 6 points when comparing 1999 and 2009. However we highlight the difficulties in comparing developmental scales, and consider whether Bayley-III overestimates developmental ability?

The pain, distress and emotional upset associated with the administration of neonatal intensive care is being increasingly recognized. We studied preterm infants' response patterns to endotracheal suctioning, one of the most distressing procedures performed during neonatal intensive care. The neurobehavioural and physiological responses of 15 preterm infants were examined. The study parameters were infant body movement responses (distal limb, proximal limb, truncal), heart rate and oxygen saturation values. The infants' movements were recorded with a video camera. Heart rate and oxygen saturation were recorded with an Ivy monitor. Observations were made before (for 2 minutes), throughout and after (for 2 minutes), endotracheal suctioning. During endotracheal suctioning the infants displayed a significant alteration in neurobehaviour with increased distal limb, proximal limb and truncal movements. There was a significant change in the median heart rate, heart rate variability, median oxygen satura...

Model 1 explained 37 % of the variance in total body T-score, F (4, 253) = 39.43, p < 0.001. Model 2 explained a further 3 % of the variance, F (11, 246) = 16.28, p < 0.001. Model 3 explained a further 1 % of the variance, F (15, 242) = 13.00, p < 0.001. The main variables which explained most of the variance in total body T score were increasing age, which was associated with lower BMD ( b= - 0.26; p = 0.001), higher percentage body fat, which was associated with higher BMD ( b= 0.225; p = 0.048), higher fat free mass (FFM), which was associated with higher BMD ( b= 0.385; p < 0.001) and current smoking which was negatively associated with BMD ( b= - 0.163; p = 0.001). Within this cohort, BTM did not explain any of the variance in BMD, albeit the obvious risk factors of increasing age and smoking were associated with a lower total body BMD, whereas weight (FM and FFM) were associated with a higher BMD. Similar findings have been reported recently by others (4,5) . In conclusion, findings from this study indicate that there is a relationship between FFM and BMD, suggesting that muscle weight has an additional predictive value over fat mass and, together with exercise, may potentially help to prevent osteoporosis.

Genetic factors explain about 80 % of bone strength (1) , however, bone mineral density (BMD) and bone metabolism are also affected by a number of environmental, hormonal and modifiable lifestyle factors, of which diet has been shown to play a prominent role (2) . Oestrogen depletion that occurs during the menopause has a negative effect on BMD, putting post-menopausal women at a greater risk of low BMD or osteoporosis (3) . The aim of this study was to compare intakes of macro- and micronutrients associated with bone health, between women with osteopenia and those with a normal BMD. Post-menopausal women (n 300) (45–75 years) were recruited between October 2008 and June 2009. Nutrient intakes were estimated for 291 women from 4-d food diaries. BMD was measured in the first to fourth lumbar vertebrae (L1–L4) and left proximal femur by dual-energy X-ray absorptiometry. Osteopenic women had significantly lower estimated dietary intakes of Ca, P and protein than those with normal BMD, with intakes of Ca below the UK reference nutrient intakes (RNI) (4) (Table 1). Spearman’s rank analysis revealed a positive correlation between protein intake (g/d) and femoral BMD (r = 0.02, P = 0.041), albeit no relationship between dietary Ca or P and BMD was found. Both groups had median intakes of Mg and vitamin D below the RNI.

The authors present a new calculation of the statistical cumulants of -ln mod t mod 2 and Theta where t= mod t mod exp(i Theta ) is the transmission of a one-dimensional (1D) disordered system. They find that both variables are normally distributed in the long-length limit, and that in general the distributions obey a two-parameter scaling. However, it does not follow that the distributions of mod t mod 2 or 1/ mod t mod 2 are log-normal. They find that mod t mod 2 is never log-normal while 1/ mod t mod 2 is so only for weak disorder. For the 1D Anderson model they show that there is a crossover to a single-parameter scaling in the weak-disorder limit.

Recovery from the debilitating effects of ischaemic stroke is variable and unpredictable. To maximize patient recovery, a greater understanding of the molecular mechanisms involved in regulating both apoptosis and the repair processes affecting neuronal protection, particularly in the penumbra region, is desirable. We have previously shown, in human subjects, the increased expression of several growth factors soon after stroke, together with appearance of tyrosine phosphorylated proteins, in particular mitogen activated protein (MAP) kinase (ERK1/2). In this paper, we demonstrate a relatively short-lasting (12 h), but substantial increase in expression of phosphorylated proteins, in particular, p-JNK (phosphorylated c-Jun N-terminal kinase) and p-ERK1/2 in both the grey matter penumbra and infarcted tissue of rats, following permanent middle cerebral artery occlusion. p-ERK1/2 was associated with neurones and endothelial cells in the vicinity of the infarct while p-JNK was mainly expressed in neurones. Expression of both p-MEK3/6 and p-p38 MAP kinase was also increased in neurones and astroglia, within 1 h of infarction, p-p38 remaining elevated and associated with neurones and in particular with astroglia in the penumbra region for4 days. Evidence suggests that short-term activation of these proteins may be detrimental to neuronal survival, while their transient nature makes them unlikely to support angiogenesis, revascularization and reperfusion over a period of days and weeks. On the other hand, short-medium-term up-regulation of neuronal p-JNK, p-c-Jun, p-Stat-1 and p-p38 might be a factor in the regulation of apoptosis. Therapeutic manipulation of phosphorylation/activation of these and other important signalling intermediates might form the basis of an appropriate treatment to maximize revascularization and neuronal protection after ischaemic stroke.

Ineffectual wound healing in hyperglycaemic patients suffering from diabetes mellitus is characterised by a reduction in capillary reformation (angiogenesis). Basic fibroblast growth factor (FGF-2) is secreted by fibroblasts, macrophages and in particular endothelial cells (EC) in response to tissue injury and is important in promotion of neovascularisation. Recently, glycation of FGF-2 has been shown to significantly reduce its activity in vitro. We have examined the kinetics of FGF-2 glycation and compared its ability with that of native FGF-2 to activate mitogenesis, capillary formation and associated signal transduction in bovine aortic EC (BAEC). FGF-2 was exposed to 0.25 M glucose-6-phosphate (G-6-P) for 24-72 h and the degree of glycation determined by matrix assisted laser desorption ionisation mass spectrometry. Native FGF-2 was heterogeneous with Mw in the range 15,153.6-17,903 Da. After 24 h incubation with G-6-P there was evidence of glycation, and the mass increase corresponded to addition of 2.7 mol of G-6-P residues; after 48 h, 4 mol sugar was added and this increased to 8.7 after 72 h. Dimerisation of FGF-2 was observed after 72 h of treatment. Induction of mitogenesis in BAEC was significantly reduced by 25%-40% after treatment for 48-96 h with glycated (24 h) FGF-2 (gFGF-2; 100 pg/ml-5 ng/ml; P0.05), whilst capillary tubule formation was significantly reduced by between 60% and 90% (100 pg/ml-1 ng/ml; P0.05) after 5 days compared to native FGF-2. Subsequent investigation of the signal transduction molecules associated with mitogenesis showed a reduction in FGF-2 induced tyrosine phosphorylated proteins of approximate Mw 20-150 kDa between 10 min and 24 h, in particular, mitogen activated protein kinase (MAPK)/early response kinase (ERK-1, ERK-2), after glycation. To determine the reason for reduced angiogenic activity of gFGF-2, we compared its binding characteristics to that of native FGF-2. Total binding of gFGF-2 to the cell surface was significantly reduced in BAEC analysed by FACS compared to native FGF-2 (P0.05). Further investigation using 125I-labelled differentially washed samples, demonstrated a significant reduction in gFGF-2 binding to the high affinity tyrosine kinase receptor (46%) compared to native FGF-2. In summary, glycation of FGF-2 in vitro occurs rapidly within 24 h in the presence of elevated levels of G-6-P. Glycation caused a significant reduction in the ability of FGF-2 to bind to the tyrosine kinase receptor and activate signal transduction pathways responsible for both mitogenesis and capillary formation in BAEC. These results could help to explain the mechanism behind impaired wound healing in patients with diabetes mellitus.

The aim of the study was to measure the impact of a designated Quiet period on the NICU environment and its influence on the infants' physiological and movement responses. The study group comprised 10 preterm infants on assisted ventilation (mean gestational age 28.7 wk (range 24-32 wk), mean birthweight 1,322 g (range 600-2,060 g), mean age 5.2 d). The environment in which the infants were nursed was altered in terms of reduced light, noise, staff activity and infant handling. The infants' heart rate, blood pressure, oxygen saturation and movement responses were recorded during this Quiet period and compared with a period of Normal activity. When the Quiet period was compared with the Normal period (median values), the NICU environment had significantly altered in terms of Light: Quiet period 3.0 Lux, Normal period 254.5 Lux (p0.01); Noise: Quiet period 54.0 dB, Normal period 58.0 dB (p0.01); Alarm events: Quiet period 491.5 sec, Normal period 1,180.5 sec (p0.01); Staff conversation: Quiet period 16.0 occasions per hour, Normal period 60.0 occasions per hour (p0.01); Staff activity: Quiet period 25.5 occasions per hour, Normal period 59.0 occasions per hour (p0.01); Infant handling: Quiet period 0.0 events per hour, Normal period 4.5 events per hour (p0.01). Infants' diastolic blood pressure and mean arterial pressure: median reduction of 2 mmHg for both during the Quiet period (p0.05). Infants' movements: Quiet period 14.5 movements per hour, Normal period 84.0 movements per hour (p0.05).This study demonstrates that Quiet periods are feasible for infants undergoing neonatal intensive care. The NICU environment was altered significantly for light, noise, infant handling and staff activity for a specified time period. These changes were associated with a reduced median diastolic blood pressure and mean arterial pressure and a decrease in infant movements.

Electrons and other waves show strong and complex fluctuations in the transmission coefficient, \ensuremath{\Vert}${\mathit{t}}_{\mathit{L}}$${\mathrm{\ensuremath{\Vert}}}^{2}$. A theory must accurately describe the distribution for both small \ensuremath{\Vert}${\mathit{t}}_{\mathit{L}}$${\mathrm{\ensuremath{\Vert}}}^{2}$, and for large \ensuremath{\Vert}${\mathit{t}}_{\mathit{L}}$${\mathrm{\ensuremath{\Vert}}}^{2}$ which dominate the average. We present a new method for calculating the statistical cumulants of the logarithm of the transmission, -ln\ensuremath{\Vert}${\mathit{t}}_{\mathit{L}}$${\mathrm{\ensuremath{\Vert}}}^{2}$, of a one-dimensional disordered system. In the long-wavelength limit both ln\ensuremath{\Vert}${\mathit{t}}_{\mathit{L}}$${\mathrm{\ensuremath{\Vert}}}^{2}$, and the phase of ${\mathit{t}}_{\mathit{L}}$ approach a normal distribution. This does not imply that \ensuremath{\Vert}${\mathit{t}}_{\mathit{L}}$${\mathrm{\ensuremath{\Vert}}}^{2}$ or 1/\ensuremath{\Vert}${\mathit{t}}_{\mathit{L}}$${\mathrm{\ensuremath{\Vert}}}^{2}$ obey a log-normal distribution. In fact the conductance \ensuremath{\Vert}${\mathit{t}}_{\mathit{L}}$${\mathrm{\ensuremath{\Vert}}}^{2}$ is never log normal, and the resistance 1/\ensuremath{\Vert}${\mathit{t}}_{\mathit{L}}$${\mathrm{\ensuremath{\Vert}}}^{2}$ only sometimes so.

We have recently shown that the degradation products of hyaluronan of 3 to 10 disaccharides (o-HA), but not native high molecular weight hyaluronan, can induce angiogenesis in vivo and, as such, o-HA is an important regulator of the neovascularization process. As a continuation of this work, we have studied the cytoplasmic signal transduction pathways responsible for o-HA-activated endothelial cell proliferation. We show that the addition of o-HA (1 microg/ml) to bovine aortic endothelial cells induces tyrosine phosphorylation of multiple proteins within 1 minute and that the activity remains above basal levels for at least 24 hours. Increased phosphorylation of the CD44 receptor was also observed. Pretreatment of cells with an anti-CD44-receptor antibody (5 microg/ml) or the tyrosine kinase inhibitor genistein (10 microM) inhibited both o-HA-induced proliferation (p0.05) and protein tyrosine phosphorylation. In comparison, native hyaluronan had little effect on tyrosine phosphorylation across the same time period. Protein kinase C (PKC) activity was increased 2- to 3-fold in the membranes of cells treated with o-HA, and a pretreatment with phorbol 12,13-dibutyrate (PDBu) to down-regulate PKC significantly inhibited o-HA-induced cell proliferation (p0.05). Examination by Western blotting showed that only the betaI and epsilon isoforms remained translocated to the membrane for at least 24 hours. These isoforms seem to be involved in modulating the proliferative effects of o-HA, because the transient translocation of PKC isoforms by PDBu was not sufficient to induce mitogenesis. Furthermore, we show that PKC activation of the cytoplasmic kinase cascade (Raf-1 kinase, MAP kinase kinase [MEK-1], and extracellular signal-regulated kinase [ERK-1]) by o-HA culminated in the nuclear translocation of ERK-1. This pathway is essentially linear, as shown by the ability of specific enzyme inhibitors (PDBu and PD98059) to prevent both activation of ERK-1- and o-HA-induced proliferation. We conclude that phosphorylation of the CD44 receptor results in an increase in tyrosine phosphorylation, leading to the activation of a cytoplasmic cascade and cell proliferation; this concurs with previous work, which showed that o-HA-induced proliferation of endothelial cells is CD44-receptor-mediated and accompanied by early response gene activation.

AIMS/BACKGROUND—In a prospective study the degree of distress caused by retinopathy of prematurity (ROP) screening in a cohort of preterm infants was assessed and the modifying effects of nesting in reducing their discomfort was evaluated. METHODS—38 preterm infants were included in the study. 19 infants were placed in a nest with boundaries (intervention group) and 19 infants were placed on a cot blanket (control group). Observations were made 2 minutes before, throughout, and 2 minutes after ROP examination. The factors observed were crying responses, neurobehavioural activity, and physiological changes (heart rate, oxygen saturation). Recordings were made using a video camera for crying and neurobehavioural activity and an Oxypleth monitor for heart rate and oxygen saturation. RESULTS—During ROP screening, the total group of 38 infants (nested and non-nested combined) displayed increased neurobehavioural activity (p

The aim of this study was to evaluate the efficacy of high-dose paclitaxel in patients with previously untreated stage IV epithelial ovarian cancer. Paclitaxel was administered intravenously over 3 h at a dose of 225 mg m(-2) on a 21-day cycle for six courses. Thirty-six patients were entered into this study; all 36 were assessed for toxicity and 33 patients were evaluable for response. One patient had a complete response and 12 patients had partial responses (overall response rate 39.4%, 95% CI 23-58%). The overall median duration of response was 9 months (range 3.5-23+ months). The response rate to carboplatin following failure of paclitaxel within 1 year of stopping therapy was 57% (four out of seven patients). The median survival of patients was 17.2 months. The main toxicity encountered was neutropenia which was WHO grade 3 in 11 patients (31%) and WHO grade 4 in seven patients (19%). Granulocyte colony-stimulating factor (GCSF) was not given to any patient during the study. Other toxicities were: grade 3/4 infection (11%) and nausea and vomiting (11%); grade 3 bone pain (22%), fatigue (14%), diarrhoea (3%), myalgia/arthralgia (3%) and dry eyes (3%). Transient peripheral neuropathy occurred in 16 patients (44%), and alopecia was encountered in most patients (grade 2/3, 78%). Paclitaxel given at 225 mg m(-2) to patients with stage IV epithelial ovarian cancer is active, well tolerated and does not require GCSF support.

Background Killer cell immunoglobulin like receptors (KIR) expressed on NK and T cell subsets interact with HLA ligands to influence the reactivity of these cells. The KIR/HLA genotype of an individual can affect immune responses to infection and susceptibility to autoimmunity based on the number/type of genes present ([1][1]-[3][2]). Objectives The aim of this study was to evaluate KIR/HLA-C genotypes and haplotypes in rheumatoid arthritis patients and healthy controls. Methods One hundred and fifty one rheumatoid arthritis (RA) patients and 100 healthy controls (HC) were DNA typed for 15 KIR genes and HLA-C group 1 and 2 alleles by PCR-SSP. KIR gene content in each group was determined by direct counting and broad haplotypes AA and Bx were assigned. The Bx haplotype was defined by the presence of inhibiting KIR 2DL2, 2DL5 and/or activating KIR 2DS1, 2DS2, 2DS3, 2DS5 or 3DS1. In the AA haplotype all these genes are absent. Results Comparison of individual KIR gene content between the RA group and controls did not show any significant differences. The availability of HLA-C1 and C2 ligands for inhibitory KIR was also similar between the RA and HC groups, C1/C1 (50%), C2/C2 (10%), C1/C2 (40%). Analysis of KIR genotypes and haplotype assignation revealed that the Bx haplotype which contains more than one activating KIR was significantly more frequent in the RA group compared to controls (76% vs. 60 %; P = 0.01). Conclusions Prevalence of the Bx haplotype in this RA population and subsequent availability of more activating KIR on NK and T cells could promote inflammatory responses in this disease. 1. Kakoo SI et al. HLA and NK cell inhibitory receptor genes in resolving hepatitis C infection. Science 2004; 305:872–4. 2. Nelson GW et al. Heterozygote advantage in autoimmune disease: hierarchy of protection/susceptibility conferred by HLA and killer Ig-like receptor combinations in Psoriatic arthritis. J Immunol 2004;173:4273–6 3. Hollenbach JA et al. Susceptibility to Crohn’s disease is mediated by KIR2DL2/KIR2DL3 heterozygosity and the HLA-C ligand. Immunogenetics 2009; 61:633–71. Disclosure of Interest None Declared [1]: #p-7 [2]: #p-9