Comparison of three tests for faecal calprotectin in children and young adults: a retrospective monocentric study

Objective: Faecal calprotectin is used as a sensitive marker for gastrointestinal mucosal inflammation. We compared the performance of three different assays in a large cohort of symptomatic paediatric patients. Design: Retrospective monocentric study. Setting: Inpatients and outpatients of a tertiary referral centre for paediatric gastroenterology. Participants: 304 symptomatic patients (163 males, aged 2–20 years) with active inflammatory bowel disease (IBD/A, n=130), IBD in clinical remission (IBD/R, n=62), other intestinal diseases (n=45) and controls without identified intestinal disease (n=67). Interventions: Calprotectin was measured in homogenised faecal samples with three tests (A: EliA Calprotectin, Phadia AB, Sweden; B: PhiCal, Calpro AS, Norway; C: EK-Cal, Bühlmann Laboratories, Switzerland). Outcomes: Concordance between tests was calculated using Kendall's τ coefficient. Results: IBD/A and controls were correctly classified as 97.7%/82.1% (A), 97.7%/85.1% (B) and 98.4%/62.7% (C; not significant). Test C tended to have higher calprotectin values with a lower specificity compared to tests A and B. The concordance between two tests was 0.835 for tests A and B, 0.782 for tests A and C and 0.765 for tests B and C. Conclusions: All three tests are very sensitive for detecting mucosal inflammation, but major differences exist between specificity and absolute values. It is highly advisable to use the test of the same manufacturer for follow-up and to monitor for disease activity

Comparison of three tests for faecal calprotectin in children and young adults: a retrospective monocentric study

Objective: Faecal calprotectin is used as a sensitive marker for gastrointestinal mucosal inflammation. We compared the performance of three different assays in a large cohort of symptomatic paediatric patients. Design: Retrospective monocentric study. Setting: Inpatients and outpatients of a tertiary referral centre for paediatric gastroenterology. Participants: 304 symptomatic patients (163 males, aged 2–20 years) with active inflammatory bowel disease (IBD/A, n=130), IBD in clinical remission (IBD/R, n=62), other intestinal diseases (n=45) and controls without identified intestinal disease (n=67). Interventions: Calprotectin was measured in homogenised faecal samples with three tests (A: EliA Calprotectin, Phadia AB, Sweden; B: PhiCal, Calpro AS, Norway; C: EK-Cal, Bühlmann Laboratories, Switzerland). Outcomes: Concordance between tests was calculated using Kendall's τ coefficient. Results: IBD/A and controls were correctly classified as 97.7%/82.1% (A), 97.7%/85.1% (B) and 98.4%/62.7% (C; not significant). Test C tended to have higher calprotectin values with a lower specificity compared to tests A and B. The concordance between two tests was 0.835 for tests A and B, 0.782 for tests A and C and 0.765 for tests B and C. Conclusions: All three tests are very sensitive for detecting mucosal inflammation, but major differences exist between specificity and absolute values. It is highly advisable to use the test of the same manufacturer for follow-up and to monitor for disease activity

The IGF-1R Inhibitor NVP-AEW541 Causes Insulin-Independent and Reversible Cardiac Contractile Dysfunction

The antitumor treatment NVP-AEW541 blocks IGF-1R. IGF-1R signaling is crucial for cardiac function, but the cardiac effects of NVP-AEW541 are ill defined. We assessed NVP-AEW541′s effects on cardiac function and insulin response in vivo and in isolated working hearts. We performed a dose–response analysis of NVP-AEW541 in male, 3-week-old rats and assessed the chronic effects of the clinically relevant dose in adult rats. We performed glucose tolerance tests and echocardiography; assessed the expression and phosphorylation of InsR/IGF-1R and Akt in vivo; and measured substrate oxidation, contractile function, and insulin response in the isolated working hearts. NVP-AEW541 caused dose-dependent growth retardation and impaired glucose tolerance in the juvenile rats. In the adults, NVP-AEW541 caused a continuously worsening depression of cardiac contractility, which recovered within 2 weeks after cessation. Cardiac Akt protein and phosphorylation were unchanged and associated with InsR upregulation. An acute application of NVP-AEW541 in the working hearts did not affect cardiac power but eliminated insulin’s effects on glucose and fatty acid oxidation. The systemic administration of NVP-AEW541 caused dose- and time-dependent impairment of glucose tolerance, growth, and cardiac function. Because cardiac insulin signaling was maintained in vivo but absent in vitro and because contractile function was not affected in vitro, a direct link between insulin resistance and contractile dysfunction appears unlikely

Positive effect of the fluorine moiety on the oxygen storage capacity of UiO-66 metal–organic frameworks

The capacity to store oxygen and nitrogen within UiO-66 fluorine-containing MOFs has been tested through high pressure adsorption isotherms

Whey- vs Casein-Based Enteral Formula and Gastrointestinal Function in Children With Cerebral Palsy.

Objectives: Children with severe cerebral palsy (CP) commonly have gastrointestinal (GI) dysfunction. Whey-based enteral formulas have been postulated to reduce gastroesophageal reflux (GOR) and accelerate gastric emptying (GE). The authors investigated whether whey-based (vs casein-based) enteral formulas reduce GOR and accelerate GE in children who have severe CP with a gastrostomy and fundoplication. Methods: Thirteen children received a casein-based formula for 1 week and either a 50% whey whole protein (50% WWP) or a 100% whey partially hydrolyzed protein (100% WPHP) formula for 1 week. Reflux episodes, gastric half-emptying time (GE t1/2), and reported pain and GI symptoms were measured. Results: Whey formulas emptied significantly faster than casein (median [interquartile range (IQR)] GE t1/2, 33.9 [25.3-166.2] min vs 56.6 [46-191] min; P = .033). Reflux parameters were unchanged. GI symptoms were lower in children who received 50% WWP (visual analog symptom score, median [IQR], 0[0-11.8]) vs 100% WPHP (13.0 [2.5-24.8]) (P = .035). Conclusion: This pilot study shows that in children who have severe CP with a gastrostomy and fundoplication, GE of the whey-based enteral formula is significantly faster than casein. The acceleration in GE does not alter GOR frequency, and there appears to be no effect of whey vs casein in reducing acid, nonacid, and total reflux episodes. The results indicate that enteral formula selection may be particularly important for children with severe CP and delayed GE. (JPEN J Parenter Enteral Nutr. 2012;36:118S-123S

Does Adherence Moderate the Effect of Physical or Mental Training on Episodic Memory in Older Women?

Objective: The aim was to investigate the overall amount of time spent on physical or mental activity training units (i.e., adherence) as a predictor of episodic memory performance in older healthy women. Methods: Women (N = 171, aged 70 -93 years) took part in a 6-month randomized controlled trial (physical activity or computer training, 3 times weekly). Pre-and post-intervention episodic memory and adherence were assessed. Adherence covers the objectively measured frequency of training participation including travel time to and from course sites. Results: Within the physical exercise group, adherence (β = .19, p = .03) had positive effects on cognitive performance. In the computer group, an interaction between adherence and pre-intervention episodic memory (β = −.17, p = .056) indicated improvement for low-ability women. Conclusions: Adhering to a stimulating mental or physical activity intervention is a prerequisite for healthy older women to maintain or slightly improve their episodic memory performance. Travel activity should be taken into account to cover an overall stimulation. Adherence to mental activity training indicates a moderating effect of mental activity training on episodic memory. Predominantly low-ability women improve their episodic memory performance. In contrast, adherence to physical activity training is positively associated with cognitive performance, regardless of pre-intervention episodic memory performance

Tissue memory CD4+ T cells expressing IL-7 receptor-alpha (CD127) preferentially support latent HIV-1 infection.

The primary reservoir for HIV is within memory CD4+ T cells residing within tissues, yet the features that make some of these cells more susceptible than others to infection by HIV is not well understood. Recent studies demonstrated that CCR5-tropic HIV-1 efficiently enters tissue-derived memory CD4+ T cells expressing CD127, the alpha chain of the IL7 receptor, but rarely completes the replication cycle. We now demonstrate that the inability of HIV to replicate in these CD127-expressing cells is not due to post-entry restriction by SAMHD1. Rather, relative to other memory T cell subsets, these cells are highly prone to undergoing latent infection with HIV, as revealed by the high levels of integrated HIV DNA in these cells. Host gene expression profiling revealed that CD127-expressing memory CD4+ T cells are phenotypically distinct from other tissue memory CD4+ T cells, and are defined by a quiescent state with diminished NFκB, NFAT, and Ox40 signaling. However, latently-infected CD127+ cells harbored unspliced HIV transcripts and stimulation of these cells with anti-CD3/CD28 reversed latency. These findings identify a novel subset of memory CD4+ T cells found in tissue and not in blood that are preferentially targeted for latent infection by HIV, and may serve as an important reservoir to target for HIV eradication efforts

Sustaining modified behaviours learnt in a diabetes prevention program in regional Australia : the role of social context

BackgroundThe Greater Green Triangle diabetes prevention program was conducted in primary health care setting of Victoria and South Australia in 2004--2006. This program demonstrated significant reductions in diabetes risk factors which were largely sustained at 18 month follow-up. The theoretical model utilised in this program achieved its outcomes through improvements in coping self-efficacy and planning. Previous evaluations have concentrated on the behavioural components of the intervention. Other variables external to the main research design may have contributed to the success factors but have yet to be identified. The objective of this evaluation was to identify the extent to which participants in a diabetes prevention program sustained lifestyle changes several years after completing the program and to identify contextual factors that contributed to sustaining changes.MethodsA qualitative evaluation was conducted. Five focus groups were held with people who had completed a diabetes prevention program, several years later to assess the degree to which they had sustained program strategies and to identify contributing factors.ResultsParticipants value the recruitment strategy. Involvement in their own risk assessment was a strong motivator. Learning new skills gave participants a sense of empowerment. Receiving regular pathology reports was a means of self-assessment and a motivator to continue. Strong family and community support contributed to personal motivation and sustained practice.ConclusionsFamily and local community supports constitute the contextual variables reported to contribute to sustained motivation after the program was completed. Behaviour modification programs can incorporate strategies to ensure these factors are recognised and if necessary, strengthened at the local level.<br /

Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways

Migration and proliferation of smooth muscle cells are key to a number of physiological and pathological processes, including wound healing and the narrowing of the vessel wall.Previous work has shown links between inflammatory stimuli and vascular smooth muscle cell proliferation and migration through mitogen activated protein kinase (MAPK) activation, though the molecular mechanisms of this process are poorly understood. Here we report that tribbles-1, a recently described modulator of MAPK activation controls vascular smooth muscle cell proliferation and chemotaxis via the Jun Kinase pathway. Our findings demonstrate that this regulation takes place via direct interactions between tribbles-1 and MKK4/SEK1, a Jun activator kinase. The activity of this kinase is dependent on tribbles-1 levels, whilst the activation and the expression of MKK4/SEK1 is not. In addition, tribbles-1 expression is elevated in human atherosclerotic arteries compared to non-atherosclerotic controls, suggesting that this protein may pay a role in disease in vivo. In summary, the data presented here suggest an important regulatory role for trb-1 in vascular smooth muscle cell biology