Long-term effects of clinical interventions on nutritional status in patients with chronic pancreatitis - A systematic review.

BACKGROUND AND AIMS: Malnutrition in chronic pancreatitis is complex and multifactorial, with malabsorption, pain, toxic dependencies and co-morbidities, such as diabetes, each playing a role. The aims of this systematic review were to assess the impact of nutritional intervention on markers of nutritional status in this complex patient group. MATERIALS AND METHODS: A systematic review of EMBASE and PubMed was carried out in February 2020, identifying 2620 articles. After screening to exclude those reporting short term changes (less than 3 months), with only one data point, or in the wrong population, eight papers were selected for analysis. RESULTS: Seven studies documented the impact of a nutritional intervention, one was an observational study only. Overall, studies were limited by predominantly retrospective designs, heterogenous populations and poor control of potentially confounding variables. Data could not be combined due to variability in reporting methods. All studies exploring nutritional intervention, whether that consisted of advice by a specialist dietitian, dose escalation of pancreatic enzymes, oral nutritional supplements or enteral feeding, demonstrated improved body weight and pain control, whereas patients who did not receive an intervention deteriorated nutritionally. CONCLUSION: Patients with chronic pancreatitis benefit from nutritional intervention. Further work is required to explore the impact of nutritional intervention on body composition and functional outcomes.

Long-term changes in nutritional status and body composition in patients with malignant pancreatic disease - A systematic review.

BACKGROUND AND AIMS: Patients with pancreatic cancer often experience significant deterioration in nutritional status over time. Malnutrition is complex and multifactorial, with malabsorption, pain, toxic dependencies, co-morbidities and malignant processes all playing a role. The aims of this systematic review were to assess nutritional changes over time and identify tolerance of nutritional intervention, thus identifying potential areas for further research to improve patient outcomes. MATERIALS AND METHODS: A systematic review of MEDLINE, EMBASE and PubMed was carried out in February 2020, identifying 2620 articles. After screening to exclude those reporting short-term measures, with only one data point, or in the wrong population, thirteen papers were selected for analysis (four trials in neo-adjuvant treatment, five in populations undergoing palliative treatment for pancreatic cancer, and four in mixed populations undergoing pancreatic resection). RESULTS: Overall, studies were limited by predominantly retrospective designs, and poor control of potentially confounding variables. Meta-analysis could not be performed due to heterogenicity in study design and reporting methods. Surgery in mixed cohorts did not appear to result in weight loss. Only one small intervention study was identified. Patients with pancreatic cancer experienced a decline in nutritional status, with 44-63% of patients undergoing neoadjuvant chemotherapy having low muscle mass prior to starting treatment. CONCLUSION: There is a paucity of data regarding nutritional intervention in pancreatic cancer. Future work should include the use of validated functional and clinical assessment tools to further explore the impact of nutritional intervention, and the relationship between nutritional status and outcome.

Lagged recovery of fish spatial distributions following a cold-water perturbation.

Anomalous local temperature and extreme events (e.g. heat-waves) can cause rapid change and gradual recovery of local environmental conditions. However, few studies have tested whether species distribution can recover following returning environmental conditions. Here, we tested for change and recovery of the spatial distributions of two flatfish populations, American plaice (Hippoglossoides platessoides) and yellowtail flounder (Limanda ferruginea), in response to consecutive decreasing and increasing water temperature on the Grand Bank off Newfoundland, Canada from 1985 to 2018. Using a Vector Autoregressive Spatiotemporal model, we found the distributions of both species shifted southwards following a period when anomalous cold water covered the northern sections of the Grand Bank. After accounting for density-dependent effects, we observed that yellowtail flounder re-distributed northwards when water temperature returned and exceeded levels recorded before the cold period, while the spatial distribution of American plaice has not recovered. Our study demonstrates nonlinear effects of an environmental factor on species distribution, implying the possibility of irreversible (or hard-to-reverse) changes of species distribution following a rapid change and gradual recovery of environmental conditions.

Resistant Starch Production and Glucose Release from Pre-Prepared Chilled Food: The SPUD Project.

With an increasing prevalence of diabetes worldwide, effective dietary strategies for blood glucose control are crucial. As carbohydrates make up approximately 50% of the diet, it is neither practical nor advisable to avoid them altogether. Most of the carbohydrate in the diet is derived from starch, found in potatoes, pasta, rice and bread. These foods are often processed in some way before consumption, yet little is known about the effects processing, such as chilling and reheating, has on the glycaemic response, particularly when the food is consumed in the context of a mixed meal. This article introduces the SPUD project, a BBSRC DRINC-funded initiative. Taking the potato as the model carbohydrate, this project will investigate, via in vitro and in vivo studies, the effects of domestic food processing techniques on the glycaemic response. A final study, utilising intrinsically labelled potato and a dual stable isotope methodology, will model glucose flux data to determine the underlying mechanisms of action.

Efficacy of an intermittent energy restriction diet in a primary care setting.

PURPOSE: Intermittent energy restriction (IER) is a popular weight loss (WL) strategy; however, its efficacy in clinical practice remains unknown. The present study compared the effects of IER compared to continuous energy restriction (CER) on WL and cardiometabolic risk factors in primary care. METHODS: A (self-selected) cohort study was conducted at the Rotherham Institute for Obesity (RIO), a primary care-based weight management service. 197(24% male) obese patients volunteered to participate and selected their diet group. IER participants (n = 99) consumed ~ 2600 kJ for two days/week. CER participants (n = 98) restricted their diet by ~ 2100 kJ/day below estimated requirements. Both interventions were delivered alongside RIO standard care. Changes in anthropometry and cardiometabolic disease risk markers (fasting biochemistry and blood pressure) were assessed after a 6-month intervention period and then participants were followed up again 6 months later (month 12). RESULTS: 27 IER patients (27%) and 39 CER patients (40%) completed the 6-month weight loss phase. Among completers, mean (SEM) WL was greater in the IER group at 6 months (5.4 ± 1.1% versus 2.8 ± 0.6%; p = 0.01), as were reductions in fat mass (p < 0.001) and improvements in systolic blood pressure (p < 0.001). Fasting insulin (p = 0.873) and diastolic blood pressure (p = 0.701) were reduced similarly in both groups. However, in the IER group, changes in anthropometry and blood pressure in the IER group had reverted to baseline by 12-month follow-up, whilst the CER group maintained weight loss but showed an increase in blood pressure. CONCLUSIONS: Among completers, IER resulted in superior short-term changes in anthropometry and some cardiometabolic risk factors. However, rates of attrition and weight regain were higher compared with standard care, providing important insights in the implementations of IER within a "real-life" NHS setting. TRIAL REGISTRATION NUMBER: ISRCTN31465600.

Elevated high density lipoprotein cholesterol and low grade systemic inflammation is associated with increased gut permeability in normoglycemic men.

BACKGROUND & AIMS: Serum lipids and lipoproteins are established biomarkers of cardiovascular disease risk that could be influenced by impaired gut barrier function via effects on the absorption of dietary and biliary cholesterol. The aim of this study was to examine the potential relationship between gut barrier function (gut permeability) and concentration of serum lipids and lipoproteins, in an ancillary analysis of serum samples taken from a previous study. METHODS AND RESULTS: Serum lipids, lipoproteins and functional gut permeability, as assessed by the percentage of the urinary recovery of 51Cr-labelled EDTA absorbed within 24 h, were measured in a group of 30 healthy men. Serum lipopolysaccharide, high sensitivity C-reactive protein and interleukin-6 were also measured as markers of low-grade inflammation. The group expressed a 5-fold variation in total gut permeability (1.11-5.03%). Gut permeability was unrelated to the concentration of both serum total and low density lipoprotein (LDL)-cholesterol, but was positively associated with serum high density lipoprotein (HDL)-cholesterol (r = 0.434, P = 0.015). Serum HDL-cholesterol was also positively associated with serum endotoxaemia (r = 0.415, P = 0.023). CONCLUSION: The significant association between increased gut permeability and elevated serum HDL-cholesterol is consistent with the role of HDL as an acute phase reactant, and in this situation, potentially dysfunctional lipoprotein. This finding may have negative implications for the putative role of HDL as a cardio-protective lipoprotein.

On the role of the second-order derivative term in the calculation of convergent beam diffraction patterns.

The simulation of (scanning) transmission electron microscopy images and diffraction patterns is most often performed using the forward-scattering approximation where the second-order derivative term in z is assumed to be small with respect to the first-order derivative term in the modified Schrödinger equation. This assumption is very good at high incident electron energies, but breaks down at low energies. In order to study the differences between first- and second-order methods, convergent beam electron diffraction patterns were simulated for silicon at the [111] zone-axis orientation at 20 keV and compared using electron intensity difference maps and integrated intensity profiles. The geometrical differences in the calculated diffraction patterns could be explained by an Ewald surface analysis. Furthermore, it was found that solutions based on the second-order derivative equation contained small amplitude oscillations that need to be resolved in order to ensure numerical integration stability. This required the use of very small integration steps resulting in significantly increased computation time compared to the first-order differential equation solution. Lastly, the efficiency of the numerical integration technique is discussed.

Reverse Monte Carlo reconstruction algorithm for discrete electron tomography based on HAADF-STEM atom counting.

In this paper, we propose an algorithm to obtain a three-dimensional reconstruction of a single nanoparticle based on the method of atom counting. The location of atoms in three dimensions has been successfully performed using simulations of high-angle-annular-dark-field images from only three zone-axis projections, [110], [310] and [211], for a face-centred cubic particle. These three orientations are typically accessible by low-tilt holders often used in high-performance scanning transmission electron microscopes.

Efficacy of increased resistant starch consumption in human type 2 diabetes.

Resistant starch (RS) has been shown to beneficially affect insulin sensitivity in healthy individuals and those with metabolic syndrome, but its effects on human type 2 diabetes (T2DM) are unknown. This study aimed to determine the effects of increased RS consumption on insulin sensitivity and glucose control and changes in postprandial metabolites and body fat in T2DM. Seventeen individuals with well-controlled T2DM (HbA1c 46.6±2 mmol/mol) consumed, in a random order, either 40 g of type 2 RS (HAM-RS2) or a placebo, daily for 12 weeks with a 12-week washout period in between. AT THE END OF EACH INTERVENTION PERIOD, PARTICIPANTS ATTENDED FOR THREE METABOLIC INVESTIGATIONS: a two-step euglycemic-hyperinsulinemic clamp combined with an infusion of [6,6-(2)H2] glucose, a meal tolerance test (MTT) with arterio-venous sampling across the forearm, and whole-body imaging. HAM-RS2 resulted in significantly lower postprandial glucose concentrations (P=0.045) and a trend for greater glucose uptake across the forearm muscle (P=0.077); however, there was no effect of HAM-RS2 on hepatic or peripheral insulin sensitivity, or on HbA1c. Fasting non-esterified fatty acid (NEFA) concentrations were significantly lower (P=0.004) and NEFA suppression was greater during the clamp with HAM-RS2 (P=0.001). Fasting triglyceride (TG) concentrations and soleus intramuscular TG concentrations were significantly higher following the consumption of HAM-RS2 (P=0.039 and P=0.027 respectively). Although fasting GLP1 concentrations were significantly lower following HAM-RS2 consumption (P=0.049), postprandial GLP1 excursions during the MTT were significantly greater (P=0.009). HAM-RS2 did not improve tissue insulin sensitivity in well-controlled T2DM, but demonstrated beneficial effects on meal handling, possibly due to higher postprandial GLP1.

Increased intestinal permeability to oral chromium (51 Cr) -EDTA in human Type 2 diabetes.

OBJECTIVE: In animal models of obesity and Type 2 diabetes, permeability of the intestine is increased because of impairment of tight junction proteins, allowing translocation of bacterial endotoxin and resulting in low-grade systemic inflammation. This has yet to be demonstrated in humans. The objective of this study was the demonstration of increased intestinal permeability in human Type 2 diabetes. METHODS: We examined intestinal permeability using chromium ((51) Cr)-EDTA urinary recovery in twenty well-controlled men with Type 2 diabetes compared with control subjects matched for age, gender and BMI. RESULTS: Intestinal permeability was significantly increased (P = 0.002) in the diabetic group and was correlated to increased levels of systemic inflammatory markers high-sensitivity C-reactive protein (r = 0.694, P = 0.001), interleukin 6 (r = 0.548, P = 0.012) and tumour necrosis factor alpha (r = 0.564, P = 0.010). CONCLUSION: This is the first demonstration that increased intestinal permeability may be a feature of human Type 2 diabetes.

Influence of the tolerability of vinegar as an oral source of short-chain fatty acids on appetite control and food intake.

BACKGROUND: Vinegar is promoted as a natural appetite suppressant, based on previous reports that vinegar ingestion significantly increases subsequent satiety. However there are concerns about the appropriateness and safety of this advice, and it is unclear if poor product palatability may explain previously published effects on appetite. OBJECTIVE: To investigate if vinegar palatability and tolerability have a role in suppressing appetite and food intake in two sequential and related acute human feeding studies. SUBJECTS AND METHODS: Healthy, young, normal weight unrestrained eaters were recruited to Study 1 (n=16), an acute feeding study supplying vinegar within both palatable and unpalatable drinks alongside a mixed breakfast in comparison to a non-vinegar control; and to Study 2 (n=14), a modified sham feeding study (taste only without ingestion) comparing vinegar to a non-vinegar control following a milkshake preload. Both studies were a randomized crossover balanced design for the assessment of appetite, energy intake and glycaemic response. RESULTS: In Study 1, ingestion of vinegar significantly reduced quantitative and subjective measures of appetite, which were accompanied by significantly higher nausea ratings, with unpalatable treatment having the greatest effect. Significant correlations between palatability ratings and appetite measures were found. In Study 2, orosensory stimulation with vinegar did not influence subsequent subjective or quantitative measures of appetite compared with control. CONCLUSIONS: These studies indicate that vinegar ingestion enhances satiety whereas orosensory stimulation alone does not, and that these effects are largely due to poor tolerability following ingestion invoking feelings of nausea. On this basis the promotion of vinegar as a natural appetite suppressant does not seem appropriate.

Effects of small specimen tilt and probe convergence angle on ADF-STEM image contrast of Si(0.8)Ge(0.2) epitaxial strained layers on (100) Si.

The effects of specimen tilt and probe convergence angle on annular dark field (ADF) image contrast of Si(0.8)Ge(0.2) heteroepitaxial strained layers on (100) Si were investigated in a 200 kV scanning transmission electron microscope (STEM) for a TEM specimen thickness of 195 nm. With 0.5 degrees of specimen tilt away from the exact <011> zone-axis orientation, the signal-to-noise level of atomic columns was significantly reduced for both Si(0.8)Ge(0.2) and Si in high resolution ADF-STEM lattice images. When the specimen was tilted 0.5 degrees around the <011> axis, or the STEM probe convergence semiangle was reduced from 14.3 to 3.6 mrad, the ADF-STEM image intensity profiles across the Si(0.8)Ge(0.2) and Si layers changed significantly as compared to those obtained at the exact <011> zone axis orientation, and no longer reflected the composition changes occurring across the layer structure. Multislice image simulation results revealed that the misfit strain between the Si(0.8)Ge(0.2) and Si layers, and strain relaxation near the surface of the TEM specimen, were responsible for the observed changes in image intensity.

Effects of a novel propionate-rich sourdough bread on appetite and food intake.

BACKGROUND: There is evidence linking oral propionate to a reduction in food intake, which could confer functional food properties in the fight against obesity. However, propionate is typically volatile with a pungent smell and taste and so incorporating into foods naturally, at levels acceptable to the consumer is a novel approach. SUBJECTS/METHODS: Twenty healthy, young, normal weight unrestrained eaters underwent an acute feeding study using a palatable sourdough and an identical control bread of a similar palatability, in a randomized cross-over balanced design for the assessment of appetite and energy intake. RESULTS: No difference in energy intake of an ad libitum test meal, 180 min after the bread-based breakfast or in energy and macronutrient intake over the entire 24 h period was found between breads. Visual analogue scale ratings for appetite were not influenced by bread type, except the desire to eat something sweet. Elevated plasma insulin concentrations were observed following the propionate-rich sourdough breakfast (P=0.033 no effects of treatment on postprandial glycaemia were found. CONCLUSIONS: These findings suggest propionate-rich sourdough bread does not influence appetite and food intake unlike larger doses of the food preservative N-propionate.

The AMPK stress response pathway mediates anoikis resistance through inhibition of mTOR and suppression of protein synthesis.

Suppression of anoikis after detachment of cancer cells from the extracellular matrix is a key step during metastasis. Here we show that, after detachment, mouse embryonic fibroblasts (MEFs) transformed by K-Ras(V12) or ETV6-NTRK3 (EN) activate a transcriptional response overrepresented by genes related to bioenergetic stress and the AMP-activated protein kinase (AMPK) energy-sensing pathway. Accordingly, AMPK is activated in both transformed and non-transformed cells after detachment, and AMPK deficiency restores anoikis to transformed MEFs. However, AMPK activation represses the mTOR complex-1 (mTORC1) pathway only in transformed cells, suggesting a key role for AMPK-mediated mTORC1 inhibition in the suppression of anoikis. Consistent with this, AMPK-/- MEFs transformed by EN or K-Ras show sustained mTORC1 activation after detachment and fail to suppress anoikis. Transformed TSC1-/- MEFs, which are incapable of suppressing mTORC1, also undergo anoikis after detachment, which is reversed by mTORC1 inhibitors. Furthermore, transformed AMPK-/- and TSC1-/- MEFs both have higher total protein synthesis rates than wild-type controls, and translation inhibition using cycloheximide partially restores their anoikis resistance, indicating a mechanism whereby mTORC1 inhibition suppresses anoikis. Finally, breast carcinoma cell lines show similar detachment-induced AMPK/mTORC1 activation and restoration of anoikis by AMPK inhibition. Our data implicate AMPK-mediated mTORC1 inhibition and suppression of protein synthesis as a means for bioenergetic conservation during detachment, thus promoting anoikis resistance.

Resistant starch improves insulin sensitivity in metabolic syndrome.

AIMS: Diets rich in non-viscous fibre are linked to a reduced risk of both diabetes and cardiovascular disease; however, the mechanism of action remains unclear. This study was undertaken to assess whether chronic consumption of this type of fibre in individuals with the metabolic syndrome would improve insulin sensitivity via changes in ectopic fat storage. METHODS: The study was a single-blind, randomized, parallel nutritional intervention where 20 insulin resistant subjects consumed either the fibre supplement (resistant starch) (40 g/day) or placebo supplement (0 g/day) for 12 weeks. Insulin sensitivity was measured by euglycaemic-hyperinsulinaemic clamp and ectopic fat storage measured by whole-body magnetic resonance spectroscopy. RESULTS: Resistant starch consumption did not significantly affect body weight, fat storage in muscle, liver or visceral depots. There was also no change with resistant starch feeding on vascular function or markers of inflammation. However, in subjects randomized to consume the resistant starch, insulin sensitivity improved compared with the placebo group (P = 0.023). Insulin sensitivity correlated significantly with changes in waist circumference and fat storage in tibialis muscle and to a lesser extent to visceral-to-subcutaneous abdominal adipose tissue ratio. CONCLUSION: Consumption of resistant starch improves insulin sensitivity in subjects with the metabolic syndrome. Unlike in animal models, diabetes prevention does not appear to be directly related to changes in body adiposity, blood lipids or inflammatory markers. Further research to elucidate the mechanisms behind this change in insulin sensitivity in human subjects is required.

Impact of restraint and disinhibition on PYY plasma levels and subjective feelings of appetite.

The impact of eating behaviours on circulating levels of appetite-regulating hormones remains largely unknown. The aims of this study were to assess the role of restraint and disinhibition on fasting/postprandial peptide YY (PYY) plasma levels and subjective feelings of appetite in normal-weight individuals and to determine whether the effect was energy load dependent. 33 participants (12 men) were classified as restrained/unrestrained and low/high in disinhibition based on Three Factor Eating Questionnaire-18R and Dutch Eating Behaviour Questionnaire. The impact of restraint/disinhibition on PYY plasma levels and feelings of appetite was measured, after a 500kcal and 1000kcal breakfast, using a randomised crossover design. Restraint did not impact on either fasting or postprandial PYY plasma levels, but participants with high disinhibition had a tendency towards a blunted postprandial PYY response. Moreover, restrained eaters reported lower ratings of prospective food consumption postprandially, and a tendency towards higher fullness/lower hunger. In conclusion, circulating PYY is unaffected by restrained eating behaviour, despite being associated with increased fullness and reduced hunger in the fed state. High levels of disinhibition tend to be associated with a blunted PYY response and this may contribute towards the susceptibility to overconsumption and increased risk of weight gain characteristic of this trait.

Effects of restrained eating behaviour on insulin sensitivity in normal-weight individuals.

Restrained eating behaviour has been linked to abnormalities in metabolic and endocrine functions. However, the impact of restraint on fasting insulin and glucose plasma levels and insulin sensitivity remains controversial. Moreover, the few postprandial studies to date are limited by an inappropriate sampling time frame and a low "net" energy and carbohydrate load. The aims of this study are to assess the role of dietary restraint on fasting and postprandial plasma levels of insulin, glucose, triacylglycerol (TAG) and non esterified fatty acids (NEFA) in healthy volunteers with a normal and stable body weight and to determine whether the effect of restraint on the plasma levels of the previous hormones/metabolites is load dependent. Normal-weight participants (21 women and 12 men) were classified as restrained/unrestrained based on the restraint scale of the Three Factor Eating Questionnaire-18R and Dutch Eating Behaviour Questionnaire. The impact of restraint on the plasma levels of different hormones/metabolites was measured, in response to a 500 kcal and 1000 kcal breakfast, using a randomised crossover design. Restraint was associated with lower fasting insulin plasma levels (P<0.05) and a lower insulin (P<0.015) and glucose (P<0.05) plasma levels in the postprandial state, but did not impact on TAG or NEFA. Moreover, restrained eaters showed a better fasting (P<0.05) and postprandial insulin sensitivity (P<0.01). Restrained eating behaviour has, therefore, a significant impact on both fasting and postprandial glucose metabolism, being associated with increased insulin sensitivity. These findings suggest the need for adjusting for restraint level in studies where glucose metabolism is a major outcome.

A study in the computation time required for the inclusion of strain field effects in Bloch-wave simulations of TEM diffraction contrast images.

As transmission electron microscopy (TEM) imaging techniques continue to become more quantitative, interpretation of the experimental images demands that accurate image simulations be computed incorporating all important aspects of the image including: compositional, crystallographic and microscope effects, as well as contrast due to strain fields arising from stresses created by lattice misfit or defects. Incorporation of the effects of strain fields in the simulation of diffraction-contrast TEM images in the Bloch-wave formalism requires the integration of a system of first-order differential equations in order to modify the excitation amplitudes and produce contrast in the image. This integration is computationally demanding with the time for integration scaling as the cube of the number of beams included in the calculation. In order to investigate the computational requirements of the integration, a variety of numerical integration packages were evaluated with respect to timing and accuracy in the simulation of quantum dot, spherical inclusion and screw dislocation images. It was determined that a class of Adams-multistep methods can provide a decrease in computation time ranging from 2 to 4 as compared to the standard Runge-Kutta 4(5) approach depending on the simulation conditions.