Micronutrient status of individuals with overweight and obesity following 3 months' supplementation with PolyGlycopleX (PGX®) or psyllium: a randomized controlled trial.

BACKGROUND: Safe and effective weight control strategies are needed to curtail the current obesity epidemic worldwide. Increasing dietary fibre has shown positive results with weight loss as well as in the reduction of metabolic syndrome risk factors. However, fibre can act as an inhibitor to the bioavailability of micronutrients in the gastrointestinal tract. While there is a substantial amount of scientific research into psyllium fibre, PolyGlycopleX (PGX®) is a novel fibre and as yet the effects of PGX® on micronutrient status is not well researched. AIM: To determine whether 3-months' supplementation with 15 g of psyllium or PGX® fibre daily affects micronutrient status of overweight and obese adults. METHODS: Overweight and obese individuals with a BMI between 25-40 kg/m2 and aged between 18 and 65 years, but otherwise healthy, were instructed to consume a 5 g sachet of psyllium, PGX® fibre or a rice flour placebo three times a day for 52 weeks as part of a larger long-term study. Blood sample data for the first 3 months were analysed for associations between serum micronutrient levels and psyllium fibre and/or PGX® supplements. RESULTS: No significant differences between fibre supplement groups and micronutrient status were found after 3 months at p > 0.05. Dietary intake of vitamin C was significantly lower for PGX® at 3 months compared to baseline and compared to control (p < 0.05). Folate was significantly lower in the control group after 3 months (p < 0.05). In the psyllium group, folate, sodium, zinc and magnesium intake decreased after 3 months (p < 0.05). A limitation of dietary intake data (tertiary measure) is the potential for inaccurate self-reporting, although reduced nutrient intake could be due to the satiating effect of dietary fibre. CONCLUSIONS: There were no significant between group differences in serum micronutrient concentrations after a 3-month psyllium fibre or PGX® supplementation intervention of 15 g per day. Fibre supplementation is unlikely to compromise the nutritional status of overweight and obese individuals in the short term. Further research is recommended to monitor micronutrient status over a longer period or with a higher fibre dosage.

A text-mining based analysis of 100,000 tumours affecting dogs and cats in the United Kingdom.

Cancer is a major reason for veterinary consultation, especially in companion animals. Cancer surveillance plays a key role in prevention but opportunities for such surveillance in companion animals are limited by the lack of suitable veterinary population health infrastructures. In this paper we describe a pathology-based animal tumour registry (PTR) developed within the Small Animal Veterinary Surveillance Network (SAVSNET) built from electronic pathology records (EPR) submitted to this network. From an original collection of 180232 free text (non-structured) EPRs reported between April 2018 and June 2019, we used specific text-mining methodologies to identify 109895 neoplasias. These data were normalized to describe both the tumour (type and location) and the animal (breed, neutering status and veterinary practice postcode). The resulting PTR, the largest of its kind for companion animals to date, is an important research resource being able to facilitate a wide array of research in areas including surveillance, clinical decision making and comparative cancer biology.

Overweight & obese Australian adults and micronutrient deficiency.

BACKGROUND: Micronutrients have been implicated as an important factor in regulating various metabolic processes and thus playing a role in the aetiology of obesity. Many studies have been conducted worldwide that clearly show a direct link between obesity and micronutrient deficiencies. The aim of this study was to assess the nutritional status of overweight and obese Australian adults to see if there were any associations between BMI and serum micronutrient levels. METHODS: Baseline serum micronutrient data of overweight and obese individuals with a body mass index (BMI) between 25 and 40 kg/m2 and aged between 18 and 65 years was compared to the clinical micronutrient reference ranges for associations between BMI and micronutrient status. RESULTS: There were significant negative associations between BMI and serum vitamin D (p = 0.044), folate (p = 0.025), magnesium (p = 0.010) and potassium (p = 0.023). CONCLUSIONS: Overweight and obesity appears to impact on the bioavailability and utilisation of micronutrients with absorption, excretion, storage/distribution (fat sequestering, tissue dispersion), metabolism (catabolic losses, possibly oxidative), increased physiologic requirements, and lower absolute total dietary intake being the current theory for observed differences. While vitamins D, folate, magnesium and potassium showed a negative relationship to BMI, other micronutrients did not. This may be explained by the fortification of certain processed foods, or the possibility of overweight and obese people eating more to satisfy their nutritional requirements.

Effects of daily consumption of psyllium, oat bran and polyGlycopleX on obesity-related disease risk factors: A critical review.

The persistent obesity crisis, with its increased risk for the metabolic syndrome (MetS), type 2 diabetes, and cardiovascular disease (CVD), continues to damage the health of populations globally, including children. Diets rich in the fiber provided by fruit and vegetables support good metabolic health, although few adults and children achieve the recommended daily target. Daily fiber supplementation, particularly with soluble fiber products, such as psyllium, oat bran, or a newer product such as PolyGlycopleX, may provide a convenient solution. Literature searches were conducted to identify original research articles, systematic reviews, and meta-analyses with the search terms psyllium, oat bran, PolyGlycopleX, and PGX, AND adults and children AND overweight, obesity, and metabolic syndrome. Data source was Embase and PubMed from 1980 to 2017. The results show that the addition of a soluble fiber product, most notably psyllium, improves blood lipid profiles, particularly total and low-density lipoprotein cholesterol, as well as glycemic response, and increases satiety, and by thus improving MetS and CVD risk factors, may augment the processes initiated by weight reduction diets. Although less studied than psyllium, the available evidence has shown that ß-glucan present in oat bran has a beneficial effect on MetS and CVD risk factors, particularly blood lipids and glycemia. Early research has found PolyGlycopleX to provide similar benefits to other soluble fiber products, and suggest it may also assist with weight loss. This critical review demonstrates that soluble fiber supplements used as an adjunct to dietary and lifestyle modifications may assist with the treatment of CVD and MetS risk factors. More research is needed to further clarify the benefits of PolyGlycopleX in particular, as well as to develop safe and efficacious recommendations for fiber supplementation of all types for children in general.

Identification of molecular genetic contributants to canine cutaneous mast cell tumour metastasis by global gene expression analysis.

Cutaneous mast cell tumours are one of the most common canine cancers. Approximately 25% of the tumours metastasise. Activating c-kit mutations are present in about 20% of tumours, but metastases occur in the absence of mutations. Tumour metastasis is associated with significantly diminished survival in spite of adjuvant chemotherapy. Available prognostic tests do not reliably predict whether a tumour will metastasise. In this study we compared the global expression profiles of 20 primary cutaneous mast cell tumours that metastasised with those of 20 primary tumours that did not metastasise. The objective was to identify genes associated with mast cell tumour metastatic progression that may represent targets for therapeutic intervention and biomarkers for prediction of tumour metastasis. Canine Gene 1.1 ST Arrays were employed for genome-wide expression analysis of formalin-fixed, paraffin-embedded biopsies of mast cell tumours borne by dogs that either died due to confirmed mast cell tumour metastasis, or were still alive more than 1000 days post-surgery. Decreased gene expression in the metastasising tumours appears to be associated with a loss of cell polarity, reduced cell-cell and cell-ECM adhesion, and increased cell deformability and motility. Dysregulated gene expression may also promote extracellular matrix and base membrane degradation, suppression of cell cycle arrest and apoptosis, and angiogenesis. Down-regulation of gene expression in the metastasising tumours may be achieved at least in part by small nucleolar RNA-derived RNA and microRNA-effected gene silencing. Employing cross-validation, a linear discriminant analysis-based classifier featuring 19 genes that displayed two-fold differences in expression between metastasising and non-metastasising tumours was estimated to classify metastasising and non-metastasising tumours with accuracies of 90-100% and 70-100%, respectively. The differential expression of 9 of the discriminator genes was confirmed by quantitative reverse transcription-PCR.

Quantitative Expression and Co-Localization of Wnt Signalling Related Proteins in Feline Squamous Cell Carcinoma.

Feline oral squamous cell carcinoma (FOSCC) is an aggressive neoplasm in cats. Little is known about the possible molecular mechanisms that may be involved in the initiation, maintenance and progression of FOSCC. Wnt signalling is critical in development and disease, including many mammalian cancers. In this study, we have investigated the expression of Wnt signalling related proteins using quantitative immunohistochemical techniques on tissue arrays. We constructed tissue arrays with 58 individual replicate tissue samples. We tested for the expression of four key Wnt/ß-catenin transcription targets, namely Cyclin D1 (CCND1 or CD1), FRA1, c-Myc and MMP7. All antibodies showed cross reactivity in feline tissue except MMP7. Quantitative immunohistochemical analysis of single proteins (expressed as area fraction / amount of tissue for normal vs tumor, mean ± SE) showed that the expression of CD1 (3.9 ± 0.5 vs 12.2 ± 0.9), FRA1 (5.5 ± 0.6 vs 16.8 ± 1.1) and c-Myc (5.4 ± 0.5 vs 12.5 ± 0.9) was increased in FOSCC tissue by 2.3 to 3 fold compared to normal controls (p<0.0001). By using a multilabel, quantitative fluorophore technique we further investigated if the co-localization of these proteins (all transcription factors) with each other and in the nucleus (stained with 4',6-diamidino-2-phenylindole, DAPI) was altered in FOSCC compared to normal tissue. The global intersection coefficients, a measure of the proximity of two fluorophore labeled entities, showed that there was a significant change (p < 0.01) in the co-localization for all permutations (e.g. CD1/FRA1 etc), except for the nuclear localization of CD1. Our results show that putative targets of Wnt signalling transcription are up-regulated in FOSCC with alterations in the co-localization of these proteins and could serve as a useful marker for the disease.

Proliferative and nonproliferative lesions of the rat and mouse central and peripheral nervous systems.

Harmonization of diagnostic nomenclature used in the pathology analysis of tissues from rodent toxicity studies will enhance the comparability and consistency of data sets from different laboratories worldwide. The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of four major societies of toxicologic pathology to develop a globally recognized nomenclature for proliferative and nonproliferative lesions in rodents. This article recommends standardized terms for classifying changes observed in tissues of the mouse and rat central (CNS) and peripheral (PNS) nervous systems. Sources of material include academic, government, and industrial histopathology databases from around the world. Covered lesions include frequent, spontaneous, and aging-related changes as well as principal toxicant-induced findings. Common artifacts that might be confused with genuine lesions are also illustrated. The neural nomenclature presented in this document is also available electronically on the Internet at the goRENI website (http://www.goreni.org/).

The development of sustained attention in children: the effect of age and task load.

This study explored how children's sustained attention develops and the effect of manipulating task parameters on sustained attention. The sample comprised 57 children (5-12 years) who completed CogState and Score! (Test of Everyday Attention for Children). Novel variability and traditional indices indicated rapid development from 5-6 to 8-9 years on all measures and a developmental plateau from 8-9 to 11-12, with growth evident on some measures. Findings suggest that sustained attention improves to age 10, then plateaus with only minor improvements. Further, performance was generally poorer on high load tasks compared to low load, with the same developmental pattern uncovered.

Modulation of notch processing by gamma-secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation.

It is anticipated that gamma-secretase inhibitors (gamma-Sec-I) that modulate Notch processing will alter differentiation in tissues whose architecture is governed by Notch signaling. To explore this hypothesis, Han Wistar rats were dosed for up to 5 days with 10-100 micromol/kg b.i.d. gamma-Sec-I from three chemical series that inhibit Notch processing in vitro at various potencies (Notch IC(50)). These included an arylsulfonamide (AS) (142 nM), a dibenzazepine (DBZ) (1.7 nM), and a benzodiazepine (BZ) (2.2 nM). The DBZ and BZ caused dose-dependent intestinal goblet cell metaplasia. In contrast, the AS produced no detectable in vivo toxicity, despite higher exposure to free drug. In a time course using BZ, small intestinal crypt cell and large intestinal glandular cell epithelial apoptosis was observed on days 1-5, followed by goblet cell metaplasia on days 2-5 and crypt epithelial and glandular epithelial regenerative hyperplasia on days 4-5. Gene expression profiling of duodenal samples from BZ-dosed animals revealed significant time-dependent deregulation of mRNAs for various panendocrine, hormonal, and transcription factor genes. Somatostatin, secretin, mucin, CCK, and gastrin mRNAs were elevated twofold or more by day 2, and a number of candidate "early-predictive" genes were altered on days 1-2, remaining changed for 4-5 days; these included Delta1, NeuroD, Hes1-regulated adipsin, and the Hes-regulated transcriptional activator of gut secretory lineage differentiation, the rat homolog of Drosophila atonal, Rath1. Western blotting of fecal protein from BZ-and DBZ-dosed animals exhibited increased levels of both anti-Rath1 reactive protein and anti-adipsin reactive proteins, confirming their potential value as noninvasive biomarkers of intestinal goblet metaplasia.