The Eye of a Needle : Commemorating the ‘Godly Merchant’ in the Early Modern Funeral Sermon

This document is a pre-copyedited, author-produced PDF of an article accepted for publication in The Journal of Religious History, Literature and Culture following peer review. Under embargo until 1 November 2018. The version of record [The Journal of Religious History, Literature and Culture, Vol. 3(2):70-90, November 2017] is available online at doi: https://doi.org/10.16922/jrhlc.3.2.5Peer reviewedFinal Accepted Versio

Calibrated BOLD using direct measurement of changes in venous oxygenation

Calibration of the BOLD signal is potentially of great value in providing a closer measure of the underlying changes in brain function related to neuronal activity than the BOLD signal alone, but current approaches rely on an assumed relationship between cerebral blood volume (CBV) and cerebral blood flow (CBF). This is poorly characterised in humans and does not reflect the predominantly venous nature of BOLD contrast, whilst this relationship may vary across brain regions and depend on the structure of the local vascular bed. This work demonstrates a new approach to BOLD calibration which does not require an assumption about the relationship between cerebral blood volume and cerebral blood flow. This method involves repeating the same stimulus both at normoxia and hyperoxia, using hyperoxic BOLD contrast to estimate the relative changes in venous blood oxygenation and venous CBV. To do this the effect of hyperoxia on venous blood oxygenation has to be calculated, which requires an estimate of basal oxygen extraction fraction, and this can be estimated from the phase as an alternative to using a literature estimate. Additional measurement of the relative change in CBF, combined with the blood oxygenation change can be used to calculate the relative change in CMRO2 due to the stimulus. CMRO2 changes of 18 ± 8% in response to a motor task were measured without requiring the assumption of a CBV/CBF coupling relationship, and are in agreement with previous approaches

Distinct abnormalities of small bowel and regional colonic volumes in subtypes of irritable bowel syndrome revealed by MRI

OBJECTIVES: Non-invasive biomarkers which identify different mechanisms of disease in subgroups of irritable bowel syndrome (IBS) could be valuable. Our aim was to seek useful magnetic resonance imaging (MRI) parameters that could distinguish each IBS subtypes. METHODS: 34 healthy volunteers (HV), 30 IBS with diarrhea (IBS-D), 16 IBS with constipation (IBS-C), and 11 IBS with mixed bowel habit (IBS-M) underwent whole-gut transit and small and large bowel volumes assessment with MRI scans from t=0 to t=360 min. Since the bowel frequency for IBS-M were similar to IBS-D, IBS-M and IBS-D were grouped together and labeled as IBS non-constipation group (IBS-nonC). RESULTS: Median (interquartile range): fasting small bowel water content in IBS-nonC was 21 (10–42), significantly less than HV at 44 ml (15–70), P<0.01 as was the postprandial area under the curve (AUC) P<0.01. The fasting transverse colon volumes in IBS-C were significantly larger at 253 (200–329) compared with HV, IBS-nonC whose values were 165 (117–255) and 198 (106–270) ml, respectively, P=0.02. Whole-gut transit time for IBS-C was prolonged at 69 (51–111), compared with HV at 34 (4–63) and IBS-D at 34 (17–78) h, P=0.03. Bloating score (VAS 0–10 cm) correlated with transverse colon volume at t=405 min, Spearman r=0.21, P=0.04. CONCLUSIONS: The constricted small bowel in IBS-nonC and the dilated transverse colon in IBS-C point to significant differences in underlying mechanisms of disease

Colon hypersensitivity to distension, rather than excessive gas production, produces carbohydrate-related symptoms in individuals with irritable bowel syndrome

Background & Aims: Poorly digested, fermentable carbohydrates may induce symptoms of irritable bowel syndrome (IBS), via unclear mechanisms. We performed a randomized trial with magnetic resonance imaging (MRI) analysis to investigate correlations between symptoms and changes in small and large bowel contents following oral challenge. Methods: We performed a 3-period crossover study of 29 adult patients with IBS (based on Rome III criteria, with symptoms of abdominal pain or discomfort for at least 2 days/week) and reported bloating. In parallel we performed the same study of 29 healthy individuals (controls). Studies were performed in the United Kingdom from January 2013 through February 2015. On 3 separate occasions (at least 7 days apart), subjects were given a 500 ml drink containing 40 g of carbohydrate (glucose in the first period, fructose in the second, and inulin in the third, in a random order). Levels of breath hydrogen were measured and intestinal content was assessed by MRI before and at various time points after consumption of each drink. Symptoms were determined based on subjects’ responses to the Hospital Anxiety and Depression Scale questionnaire and the Patient Health Questionnaire-15. The primary endpoint was whether participants had a clinically important symptom response during the 300 minutes following consumption of the drink. Results: More patients with IBS reached the pre-defined symptom threshold after intake of inulin (13/29) or fructose (11/29) than glucose (6/29). Symptoms peaked sooner after intake of fructose than inulin. Fructose increased small bowel water content in both patients and controls whereas inulin increased colonic volume and gas in both. Fructose and inulin increased breath hydrogen levels in both groups, compared to glucose; fructose produced an earlier increase than inulin. Controls had lower symptom scores during the period after drink consumption than patients with IBS, despite similar MRI parameters and breath hydrogen responses. In patients who reached the symptom threshold after inulin intake, peak symptom intensity correlated with peak colonic gas (r = 0.57; P<0.05). Changes in MRI features and peak breath hydrogen levels were similar in patients who did and did not reach symptom threshold. Conclusions: Patients with IBS and healthy individuals without IBS (controls) have similar physiological responses following intake of fructose or inulin; patients more frequently report symptoms after inulin than controls. In patients with a response to inulin, symptoms relate to levels of intra-luminal gas, but peak gas levels do not differ significantly between responders, non-responders or controls. This indicates that colonic hypersensitivity to distension, rather than excessive gas production, produces carbohydrate-related symptoms in patients with IBS. Clinicaltrials.gov no: NCT0177685

Glycemic, Gastrointestinal, Hormonal and Appetitive Responses to Pearl Millet or Oats Porridge Breakfasts: a Randomized, Crossover Trial in Healthy Humans

Whole grain cereal breakfast consumption has been associated with beneficial effects on glucose and insulin metabolism as well as satiety. Pearl millet is a popular ancient grain variety that can be grown in hot, dry regions. However, little is known about its health effects. This study investigated the effect of a pearl millet porridge (PMP) compared with a well-known Scottish oats porridge (SOP) on glycaemic, gastrointestinal, hormonal and appetitive responses. In a randomized, two way crossover trial, 26 healthy participants consumed two iso-energetic/volumetric PMP or SOP breakfast meals, served with a drink of water. Blood samples for glucose, insulin, GLP-1, GIP and PYY, gastric volumes and appetite ratings were collected for two hours postprandially, followed by an ad libitum meal and food intake records for the remainder of the day. The incremental area under the curve (iAUC2h) for blood glucose was not significantly different between the porridges (p ˃ 0.05). The iAUC2h gastric volume was larger for PMP compared with SOP (p = 0.045). The iAUC2h GIP concentration was significantly lower for PMP compared with SOP (p = 0.001). Other hormones and appetite responses were similar between meals. In conclusion, this study reports, for the first time, data on glycaemic and physiological responses to a pearl millet breakfast, showing that this ancient grain could represent a sustainable, alternative, with health-promoting characteristics comparable to oats. GIP is an incretin hormone linked to triacylglycerol absorption in adipose tissue, therefore the lower GIP response for PMP may be an added health benefit

Magnetic resonance imaging quantification of fasted state colonic liquid pockets in healthy humans

The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent on the volume of liquid in the gastrointestinal tract (GIT). However, little is known about the time course of GIT liquid volumes after drinking a glass of water (8 oz), particularly in the colon, which is a targeted site for both locally and systemically acting drug products. Previous magnetic resonance imaging (MRI) studies offered novel insights on GIT liquid distribution in fasted humans in the stomach and small intestine, and showed that freely mobile liquid in the intestine collects in fairly distinct regions or “pockets”. Based on this previous pilot data, we hypothesized that (1) it is possible to quantify the time course of the volume and number of liquid pockets in the undisturbed colon of fasted healthy humans following ingestion of 240 mL, using noninvasive MRI methods; (2) the amount of freely mobile water in the fasted human colon is of the order of only a few milliliters. Twelve healthy volunteers fasted overnight and underwent fasted abdominal MRI scans before drinking 240 mL (∼8 fluid ounces) of water. After ingesting the water they were scanned at frequent intervals for 2 h. The images were processed to quantify freely mobile water in the total and regional colon: ascending, transverse, and descending. The fasted colon contained (mean ± SEM) 11 ± 5 pockets of resting liquid with a total volume of 2 ± 1 mL (average). The colonic fluid peaked at 7 ± 4 mL 30 min after the water drink. This peak fluid was distributed in 17 ± 7 separate liquid pockets in the colon. The regional analysis showed that pockets of free fluid were found primarily in the ascending colon. The interindividual variability was very high; the subjects showed a range of number of colonic fluid pockets from 0 to 89 and total colonic freely mobile fluid volume from 0 to 49 mL. This is the first study measuring the time course of the number, regional location, and volume of pockets of freely mobile liquid in the undisturbed colon of fasted humans after ingestion of a glass of water. Novel insights into the colonic fluid environment will be particularly relevant to improve our understanding and design of the in vivo performance of controlled release formulations targeted to the colon. The in vivo quantitative information presented here can be input into physiologically based mechanistic models of dissolution and absorption, and can be used in the design and set up of novel in vitro performance tools predictive of the in vivo environment

Processing Apples to Puree or Juice Speeds Gastric Emptying and Reduces Postprandial Intestinal Volumes and Satiety in Healthy Adults

Background: Whole apples produce greater satiety than processed apples, but the underlying mechanisms remain unclear. Objective: Our aim was to assess the intragastric processing of apple preparations and the associated small and large bowel contents using MRI. Methods: An open label , 3-way crossover, randomized, controlled trial. 18 healthy adults [mean ± SD age, 25±4y; BMI(kg/m 2), 22.7±3.5] underwent serial MR scans on 3 occasions separated by 7d, after consumption of isocaloric (178 kcal) portions of either whole apples, apple puree or apple juice. Gastric emptying, small bowel water content (SBWC)(Primary endpoint), were measured at baseline and at 45 minutes intervals (0-270 min) post meal ingestion. Fullness and satiety were also assessed at each time point. Treatment effects between groups were analyzed using ANOVA. Results: Gastric emptying half-time (GE t 50) was greater (P < 0.0001) after participants consumed whole apple (mean ± SEM), 65 (3.3) min) compared with when they consumed apple puree (41(2.8) min) or apple juice (38 (2.9) min), times which did not differ. Postprandial AUC (135-270 min) SBWC was also greater for whole apples than puree (P = 0.025) and juice (P = 0.0004) but juice and puree did not differ. AUC for fullness and satiety (0-270 min) post-ingestion was also greater (P = 0.002 and 0.004 respectively) for whole apple compared to juice but juice and puree did not differ. Conclusions: Gastric emptying is slower after whole apples consumption causing greater sensation of fullness and satiety than puree or juice in healthy adults. Whole apples increased small bowel and colonic contents during the later phase of the study which may be relevant for subsequent food consumption. This study was registered at clinicaltrials.gov as NCT 03714464

A low FODMAP diet is associated with changes in the microbiota and reduction in breath hydrogen but not colonic volume in healthy subjects

Background & aims Ingestion of poorly digested, fermentable carbohydrates (fermentable oligo-, di-, mono-saccharides and polyols; FODMAPs) have been implicated in exacerbating intestinal symptoms and the reduction of intake with symptom alleviation. Restricting FODMAP intake is believed to relieve colonic distension by reducing colonic fermentation but this has not been previously directly assessed. We performed a randomised controlled trial comparing the effect of a low FODMAP diet combined with either maltodextrin or oligofructose on colonic contents, metabolites and microbiota. Methods A parallel randomised controlled trial in healthy adults (n = 37). All subjects followed a low FODMAP diet for a week and supplemented their diet with either maltodextrin (MD) or oligofructose (OF) 7g twice daily. Fasted assessments performed pre- and post-diet included MRI to assess colonic volume, breath testing for hydrogen and methane, and stool collection for microbiota analysis. Results The low FODMAP diet was associated with a reduction in Bifidobacterium and breath hydrogen, which was reversed by oligofructose supplementation. The difference in breath hydrogen between groups post-intervention was 27ppm (95% CI 7 to 50, P Conclusion A low FODMAP diet reduces total bacterial count and gas production with little effect on colonic volume.Peer reviewe

Increased fasting small-bowel water content in untreated coeliac disease and scleroderma as assessed by magnetic resonance imaging

Background and aims: The regular overnight migrating motor complex (MMC) ensures that the normal fasting small bowel water content (SBWC) is minimised. We have applied our recently validated non-invasive magnetic resonance technique to assess SBWC in newly diagnosed coeliac disease (CD), scleroderma (SCD) and irritable bowel syndrome (IBS) conditions, possibly associated with small intestinal bacterial overgrowth (SIBO). Methods: 20 CD and 15 SCD patients with gastrointestinal symptoms were compared to 20 healthy volunteers (HV) and 26 IBS with diarrhoea (IBS-D) patients as previously reported. All underwent a fasting, magnetic resonance imaging (MRI) scan on a 1.5 T Philips Achieva MRI scanner to assess fasting SBWC and colonic volumes. Stool and symptom diaries were completed for 1 week. Results: Median (Interquartile range, IQR) Compared to healthy volunteers, all the patients had significantly increased stool frequency and Bristol stool form score. SBWC was significantly increased in CD 109(53-224) vs. 53(31-98) mL in HV, p [less than] 0.01 and 42 (28-67) in IBS-D, p [less than] 0.01. Variable increase in SBWC was also found in SCD, median 77(39-158) but this was not significant, p=0.2. Colonic volumes were similar for all groups being 547 (442-786) for CD, 511 (453-789) for SCD, 612 (445-746) for HV and 521 (428-757) mL for IBS-D. When CD patients were subdivided according to the Marsh classification, the higher grades had larger colonic volumes.Conclusion: Fasting SBWC as assessed by MRI is significantly increased in newly diagnosed CD and SCD but decreased in IBS-D. Future studies should test whether increased resting fluid predisposes to SIBO

Glycaemic, gastrointestinal and appetite responses to breakfast porridges from ancient cereal grains: a MRI pilot study in healthy humans

Cereal grain based porridges are commonly consumed throughout the world. Whilst some data are available for varieties that are popular in the Western world such as oats and rye, other ‘ancient’ grains used in the East and in Africa such as millets are thought to have beneficial health effects, such as a suppression of post prandial hunger and circulating glucose levels. These grains, a sustainable food source due to their tolerance of extreme weather and growing conditions, are commonly found throughout Asia and Africa. However, knowledge of the physiological responses to these grain varieties is very limited. This study aimed to collect initial pilot data on the physiological and gastrointestinal responses to breakfast porridges made with two millet varieties and oats and rye grains. A total of n = 15 completed the oats and rye, n = 9 the finger millet n = 12 the pearl millet meals. MRI scans were undertaken at baseline, immediately after consumption and then hourly postprandially. Blood glucose was measured at baseline, immediately after consumption and then every 15 min until t = 80 min, then every 20 min until t = 120 min, followed on each occasion by completion of VAS. Seven participants completed the entire protocol and were included in the final analysis. A subgroup analysis with the n = 10 paired comparison between the same individuals that completed the oats, rye and pearl millet was also considered. The gastric volume AUC was higher for pearl millet than oats and rye (n = 10, p<0.001). The incremental area under the curve (iAUC) for blood glucose was not significantly different between the meals although this showed a trend to be lower for pearl millet. Hunger was lower for pearl millet compared to oats and rye (n = 10, p = 0.01). There was a significant correlation between total gastric volume AUC and average appetite AUC r = -0.47, p < 0.010. Isoenergetic breakfast porridges from ‘ancient’ varieties of millet grains showed physiological responses that were comparable with those from common Western varieties known to have beneficial health effects. Pearl millet appeared to induce lower postprandial blood glucose response and appetite scores though the differences were not conclusive compared with the other porridges and further work is needed. Improved knowledge of the effects of different cereal grains could help direct dietary advice and ultimately improve health outcomes in the general population worldwide