Is CT-based body composition associated with long-term chemotherapy-induced peripheral neuropathy in colorectal cancer survivors?

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect among colorectal cancer (CRC) survivors, and the severity is mainly dependent on the chemotherapy dose. Nowadays, chemotherapy dose is based on body surface area, while determination based on more accurate measures of body composition may be better. This study aimed to investigate the association between body composition and long-term CIPN among CRC survivors 2–11 years after diagnosis. METHODS: Data from CRC survivors from the population-based PROFILES registry were used. Survivors were included when they received chemotherapy, filled in the EORTC QLQ-CIPN20, and had a computed tomography (CT) scan at diagnosis (n = 202). Total, sensory, motor, and autonomic CIPN were based upon the EORTC QLQ-CIPN20. The abdominal CT scans were used to determine skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT). Logistic regression was used to analyze the association between CIPN outcomes and body composition variables. RESULTS: CIPN was experienced by 64% of the CRC survivors several years after chemotherapy. More SAT was associated with a higher odds of reporting total CIPN (OR = 1.01 95% CI 1.00–1.01, p = 0.01), motor CIPN (OR = 1.01 95% CI 1.00–1.01, p = 0.01), and sensory CIPN (OR = 1.01 95% CI 1.00–1.01, p = 0.04). No associations of other body composition parameters with CIPN were observed. CONCLUSION: Only SAT was associated with total, motor, and sensory CIPN. Based on these results, we cannot conclude that determining the chemotherapy dose based on body composition is preferred over determining the chemotherapy dose based on body surface to prevent CIPN. More research is needed to assess associations of body composition with CIPN, a common side effect of chemotherapy

ICAM- melanoma cells are relatively resistant to CD3-mediated T-cell lysis

Abstract The primary activation pathway of T cells is via the T-cell receptor (TCR)/CD3 complex, which is functionally interrelated with various accessory molecules. We examined the contribution of the lymphocyte-function-associated antigenI/intercellular adhesion molecule I (LFA-I/ICAM-I) interaction to CD3/TCR-mediated lysis by cytotoxic T lymphocytes (CTL). We used ICAM-I-or+ tumor cell lines as target cells and anti-CD3- or anti-LFA-I containing hetero-cross-linked monoclonal antibody (MAb) to bridge CTL and target cells and simultaneously to activate CTL. The ICAM-I- melanoma-derived cell line lgR39 was relatively resistant to CD3-mediated lysis by both TCRαβ+ and TCRγdL+ CTL, when compared with ICAM-I+ cell lines. Induction of ICAM-I on the membrane of lgR39 cells by tumor necrosis factor (TNF) rendered these cells more susceptible to CD3-mediated lysis. Anti-ICAM-I MAb inhibited this TNF-enhanced susceptibility to lysis, directly demonstrating that the induction of ICAM-I was critical in the TNF-induced increase in susceptibility to lysis of lgR39 cells. CTL formed less efficient conjugates with the ICAM-I- cells as compared to ICAM-I+ cells. Both spontaneous and CD3-induced conjugate formation as well as CD3-mediated lysis of ICAM-I- tumor cells by CTL were enhanced by the addition of anti-LFA-I containing heterocross-linked MAb, thereby mimicking the LFA-I/ICAM-I interaction between CTL and target cells. Soluble anti-CD18 MAb inhibited CD3-mediated lysis of ICAM-I- target cells by CTL without affecting their conjugate formation. Anti-LFA-I MAb added after conjugate formation still inhibited lysis of both ICAM-I+or- tumor cells. Taken together, these findings suggest that the LFA-I/ICAM-I interaction co-activates CD3/TCR-mediated lysis by CTL through both an enhanced CTL-target cell binding and the delivery of post-conjugate costimulatory signals

Coastal engineers embrace nature: characterizing the metamorphosis in hydraulic engineering in terms of Four Continua

Hydraulic engineering infrastructures, such as reservoirs, dikes, breakwaters, and inlet closures, have significantly impacted ecosystem functioning over the last two centuries. Currently, nature-based solutions are receiving increasing attention in hydraulic engineering projects and research programs. However, there is a lack of reflection on the concomitant, fundamental changes occurring in the field of hydraulic engineering, and coastal engineering in particular, and what this could mean for sustainability. In this article, we signal the shift from conventional to ecosystem-based hydraulic engineering design and characterize this in terms of four continua: (i) the degree of inclusion of ecological knowledge, (ii) the extent to which the full infrastructural lifecycle is addressed, (iii) the complexity of the actor arena taken into account, and (iv) the resulting form of the infrastructural artefact. We support our arguments with two carefully selected, iconic examples from the Netherlands and indicate how the stretching ideals of ecosystem-based engineering could engender further shifts towards sustainability

Understanding the experience of social housing pathways

This report is part of an Australian Housing and Urban Research Institute (AHURI) Inquiry examining how social housing pathways could be reimagined to provide more effective assistance for low-income households in Australia. This research sets out to understand the ways in which individuals and households experience pathways into, within and out of the Australian social housing system

Groei van de beverpopulatie: lusten en lasten

Het aantal bevers is in Nederland sterk gegroeid. In 1988 werden de eerste dieren losgelaten in de Biesbosch, en in 2012 wordt het aantal Nederlandse bevers al geschat op zeker 600 volwassen dieren. Bevers zijn door hun bijzondere gedrag een aanwinst voor onze natuur. Maar ditzelfde gedrag kan ook leiden tot overlast. Hoe ga je hiermee om

Variants in MARC1 and HSD17B13 reduce severity of NAFLD in children, perturb phospholipid metabolism, and suppress fibrotic pathways

Background & aims: Genome-wide association studies in adults have identified variants in HSD17B13 and MARC1 as protective against NAFLD. It is not known if they are similarly protective in children and, more generally, whether the peri-portal inflammation of pediatric NAFLD and lobular inflammation seen in adults share common genetic influences. Therefore, we aimed to: establish if these variants are associated with NAFLD in children, and to investigate the function of these variants in hepatic metabolism using metabolomics. Methods: 960 children (590 with NAFLD, 394 with liver histology) were genotyped for rs72613567T>TA in HSD17B13, rs2642438G>A in MARC1. Genotype-histology associations were tested using ordinal regression. Untargeted hepatic proteomics and plasma lipidomics were performed in a subset of samples. In silico tools were used to model the effect of rs2642438G>A (p.Ala165Thr) on MARC1. Results: rs72613567T>TA in HSD17B13 was associated with lower odds of NAFLD diagnosis (OR 0.7 (95%CI 0.6-0.9) and lower grade of portal inflammation (PA in MARC1 was associated with lower grade of hepatic steatosis (P=0.02). Proteomics found reduced expression of HSD17B13 in carriers of the protective allele, whereas MARC1 levels were not affected by genotype. Both variants showed downregulation of hepatic fibrotic pathways, upregulation of retinol metabolism and perturbation of phospholipid species. Modelling suggests that p.Ala165Thr would disrupt the stability and metal-binding of MARC1. Conclusions: There are shared genetic mechanisms between pediatric and adult NAFLD, despite their differences in histology. MARC1 and HSD17B13 are involved in phospholipid metabolism and suppress fibrosis in NAFLD

Quantitative trait loci conferring grain mineral nutrient concentrations in durum wheat 3 wild emmer wheat RIL population

Mineral nutrient malnutrition, and particularly deficiency in zinc and iron, afflicts over 3 billion people worldwide. Wild emmer wheat, Triticum turgidum ssp. dicoccoides, genepool harbors a rich allelic repertoire for mineral nutrients in the grain. The genetic and physiological basis of grain protein, micronutrients (zinc, iron, copper and manganese) and macronutrients (calcium, magnesium, potassium, phosphorus and sulfur) concentration was studied in tetraploid wheat population of 152 recombinant inbred lines (RILs), derived from a cross between durum wheat (cv. Langdon) and wild emmer (accession G18-16). Wide genetic variation was found among the RILs for all grain minerals, with considerable transgressive effect. A total of 82 QTLs were mapped for 10 minerals with LOD score range of 3.2–16.7. Most QTLs were in favor of the wild allele (50 QTLs). Fourteen pairs of QTLs for the same trait were mapped to seemingly homoeologous positions, reflecting synteny between the A and B genomes. Significant positive correlation was found between grain protein concentration (GPC), Zn, Fe and Cu, which was supported by significant overlap between the respective QTLs, suggesting common physiological and/or genetic factors controlling the concentrations of these mineral nutrients. Few genomic regions (chromosomes 2A, 5A, 6B and 7A) were found to harbor clusters of QTLs for GPC and other nutrients. These identified QTLs may facilitate the use of wild alleles for improving grain nutritional quality of elite wheat cultivars, especially in terms of protein, Zn and Fe

Organising knowledge generation and dissemination in the Dutch high-water protection programme–a sender-receiver approach

In 2012 the Dutch High-Water Protection Programme (HWPP) was initiated. This programme prioritised dike strengthening projects for the near future with a yearly budget of around 350 million Euros. A safety assessment 2011–2013 indicated the need to strengthen 748 km of dikes. To achieve this, it was recognised that generation and dissemination of state-of-the-art-knowledge was necessary. For this purpose, four Spatial and Technical Research Projects (STRPs) were initiated. The challenge for these STRPs is to generate and disseminate the developed knowledge that is relevant for other dike strengthening projects within the HWPP. This paper examines whether the STRPs have successfully undertaken activities to generate and disseminate new knowledge to relevant stakeholders. We examine how the generation and dissemination of knowledge from the STRPs to the HWP