Effect of Training on the Reliability of Satiety Evaluation and Use of Trained Panellists to Determine the Satiety Effect of Dietary Fibre: A Randomised Controlled Trial

Background: The assessment of satiety effects on foods is commonly performed by untrained volunteers marking their perceived hunger or fullness on line scales, marked with pre-set descriptors. The lack of reproducibility of satiety measurement using this approach however results in the tool being unable to distinguish between foods that have small, but possibly important, differences in their satiety effects. An alternate approach is used in sensory evaluation; panellists can be trained in the correct use of the assessment line-scale and brought to consensus on the meanings of descriptors used for food quality attributes to improve the panel reliability. The effect of training on the reliability of a satiety panel has not previously been reported. Method: In a randomised controlled parallel intervention, the effect of training in the correct use of a satiety labelled magnitude scale (LMS) was assessed versus no-training. The test-retest precision and reliability of two hour postprandial satiety evaluation after consumption of a standard breakfast was compared. The trained panel then compared the satiety effect of two breakfast meals containing either a viscous or a non-viscous dietary fibre in a crossover trial.Results: A subgroup of the 23 panellists (n = 5) improved their test re-test precision after training. Panel satiety area under the curve, “after the training” intervention was significantly different to “before training” (p < 0.001). Reliability of the panel determined by intraclass correlation (ICC) of test and retest showed improved strength of the correlation from 0.70 pre-intervention to 0.95 post intervention. The trained “satiety expert panel” determined that a standard breakfast with 5g of viscous fibre gave significantly higher satiety than with 5g non-viscous fibre (area under curve (AUC) of 478.2, 334.4 respectively) (p ≤ 0.002). Conclusion: Training reduced between panellist variability. The improved strength of test-retest ICC as a result of the training intervention suggests that training satiety panellists can improve the discriminating power of satiety evaluation

Association between Urinary Excretion of Cortisol and Markers of Oxidatively Damaged DNA and RNA in Humans

Chronic psychological stress is associated with accelerated aging, but the underlying biological mechanisms are not known. Prolonged elevations of the stress hormone cortisol is suspected to play a critical role. Through its actions, cortisol may potentially induce oxidatively generated damage to cellular constituents such as DNA and RNA, a phenomenon which has been implicated in aging processes. We investigated the relationship between 24 h excretion of urinary cortisol and markers of oxidatively generated DNA and RNA damage, 8-oxo-7,8-dihydro-2′-deoxyguanosine and 8-oxo-7,8-dihydroguanosine, in a sample of 220 elderly men and women (age 65 – 83 years). We found a robust association between the excretion of cortisol and the oxidation markers (R2 = 0.15, P<0.001 for both markers). Individuals in the highest quartile of cortisol excretion had a 57% and 61% higher median excretion of the DNA and RNA oxidation marker, respectively, than individuals in the lowest quartile. The finding adds support to the hypothesis that cortisol-induced damage to DNA/RNA is an explanatory factor in the complex relation between stress, aging and disease

Impaired Carbohydrate Digestion and Transport and Mucosal Dysbiosis in the Intestines of Children with Autism and Gastrointestinal Disturbances

Gastrointestinal disturbances are commonly reported in children with autism, complicate clinical management, and may contribute to behavioral impairment. Reports of deficiencies in disaccharidase enzymatic activity and of beneficial responses to probiotic and dietary therapies led us to survey gene expression and the mucoepithelial microbiota in intestinal biopsies from children with autism and gastrointestinal disease and children with gastrointestinal disease alone. Ileal transcripts encoding disaccharidases and hexose transporters were deficient in children with autism, indicating impairment of the primary pathway for carbohydrate digestion and transport in enterocytes. Deficient expression of these enzymes and transporters was associated with expression of the intestinal transcription factor, CDX2. Metagenomic analysis of intestinal bacteria revealed compositional dysbiosis manifest as decreases in Bacteroidetes, increases in the ratio of Firmicutes to Bacteroidetes, and increases in Betaproteobacteria. Expression levels of disaccharidases and transporters were associated with the abundance of affected bacterial phylotypes. These results indicate a relationship between human intestinal gene expression and bacterial community structure and may provide insights into the pathophysiology of gastrointestinal disturbances in children with autism

Regulation of Signaling at Regions of Cell-Cell Contact by Endoplasmic Reticulum-Bound Protein-Tyrosine Phosphatase 1B

Protein-tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed PTP that is anchored to the endoplasmic reticulum (ER). PTP1B dephosphorylates activated receptor tyrosine kinases after endocytosis, as they transit past the ER. However, PTP1B also can access some plasma membrane (PM)-bound substrates at points of cell-cell contact. To explore how PTP1B interacts with such substrates, we utilized quantitative cellular imaging approaches and mathematical modeling of protein mobility. We find that the ER network comes in close proximity to the PM at apparently specialized regions of cell-cell contact, enabling PTP1B to engage substrate(s) at these sites. Studies using PTP1B mutants show that the ER anchor plays an important role in restricting its interactions with PM substrates mainly to regions of cell-cell contact. In addition, treatment with PTP1B inhibitor leads to increased tyrosine phosphorylation of EphA2, a PTP1B substrate, specifically at regions of cell-cell contact. Collectively, our results identify PM-proximal sub-regions of the ER as important sites of cellular signaling regulation by PTP1B

Minimal Length Scale Scenarios for Quantum Gravity

We review the question of whether the fundamental laws of nature limit our ability to probe arbitrarily short distances. First, we examine what insights can be gained from thought experiments for probes of shortest distances, and summarize what can be learned from different approaches to a theory of quantum gravity. Then we discuss some models that have been developed to implement a minimal length scale in quantum mechanics and quantum field theory. These models have entered the literature as the generalized uncertainty principle or the modified dispersion relation, and have allowed the study of the effects of a minimal length scale in quantum mechanics, quantum electrodynamics, thermodynamics, black-hole physics and cosmology. Finally, we touch upon the question of ways to circumvent the manifestation of a minimal length scale in short-distance physics.Comment: Published version available at http://www.livingreviews.org/lrr-2013-

Evaluation of prognostic risk models for postoperative pulmonary complications in adult patients undergoing major abdominal surgery: a systematic review and international external validation cohort study

Background Stratifying risk of postoperative pulmonary complications after major abdominal surgery allows clinicians to modify risk through targeted interventions and enhanced monitoring. In this study, we aimed to identify and validate prognostic models against a new consensus definition of postoperative pulmonary complications. Methods We did a systematic review and international external validation cohort study. The systematic review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE and Embase on March 1, 2020, for articles published in English that reported on risk prediction models for postoperative pulmonary complications following abdominal surgery. External validation of existing models was done within a prospective international cohort study of adult patients (≥18 years) undergoing major abdominal surgery. Data were collected between Jan 1, 2019, and April 30, 2019, in the UK, Ireland, and Australia. Discriminative ability and prognostic accuracy summary statistics were compared between models for the 30-day postoperative pulmonary complication rate as defined by the Standardised Endpoints in Perioperative Medicine Core Outcome Measures in Perioperative and Anaesthetic Care (StEP-COMPAC). Model performance was compared using the area under the receiver operating characteristic curve (AUROCC). Findings In total, we identified 2903 records from our literature search; of which, 2514 (86·6%) unique records were screened, 121 (4·8%) of 2514 full texts were assessed for eligibility, and 29 unique prognostic models were identified. Nine (31·0%) of 29 models had score development reported only, 19 (65·5%) had undergone internal validation, and only four (13·8%) had been externally validated. Data to validate six eligible models were collected in the international external validation cohort study. Data from 11 591 patients were available, with an overall postoperative pulmonary complication rate of 7·8% (n=903). None of the six models showed good discrimination (defined as AUROCC ≥0·70) for identifying postoperative pulmonary complications, with the Assess Respiratory Risk in Surgical Patients in Catalonia score showing the best discrimination (AUROCC 0·700 [95% CI 0·683–0·717]). Interpretation In the pre-COVID-19 pandemic data, variability in the risk of pulmonary complications (StEP-COMPAC definition) following major abdominal surgery was poorly described by existing prognostication tools. To improve surgical safety during the COVID-19 pandemic recovery and beyond, novel risk stratification tools are required. Funding British Journal of Surgery Society