Long-term impact of the low-FODMAP diet on gastrointestinal symptoms, dietary intake, patient acceptability, and healthcare utilization in irritable bowel syndrome

Background: The low-FODMAP diet is a frequently used treatment for irritable bowel syndrome (IBS). Most research has focused on short-term FODMAP restriction; however, guidelines recommend that high-FODMAP foods are reintroduced to individual tolerance. This study aimed to assess the long-term effectiveness of the low-FODMAP diet following FODMAP reintroduction in IBS patients. Methods: Patients with IBS were prospectively recruited to a questionnaire study following completion of dietitian-led low-FODMAP education. At baseline and following FODMAP restriction (short term) only, gastrointestinal symptoms were measured as part of routine clinical care. Following FODMAP reintroduction, (long term), symptoms, dietary intake, acceptability, food-related quality of life (QOL), and healthcare utilization were assessed. Data were reported for patients who continued long-term FODMAP restriction (adapted FODMAP) and/or returned to a habitual diet (habitual). Key Results: Of 103 patients, satisfactory relief of symptoms was reported in 12% at baseline, 61% at short-term follow-up, and 57% at long-term follow-up. At long-term follow-up, 84 (82%) patients continued an ‘adapted FODMAP’ diet (total FODMAP intake mean 20.6, SD 14.9\ua0g/d) compared with 19 (18%) of patients following a ‘habitual’ diet (29.4, SD 22.9\ua0g/d, P=.039). Nutritional adequacy was not compromised for either group. The ‘adapted FODMAP’ group reported the diet cost significantly more than the ‘habitual’ group (

A Large Energy Barrier Prevents Rapid Redissolution of Fibrillar Amyloid

<div><p>In this issue of <i>PLoS Medicine</i>, Borchelt and colleagues demonstrate in the living amyloid-laden mouse brain that Aβ plaques are cleared very slowly, even if synthesis of new Aβ precursor molecules is extinguished using a tet-off system [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020417#pmed-0020417-b7" target="_blank">7</a>]. In the recent, relevant, but independent, X-ray crystallography study [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020417#pmed-0020417-b8" target="_blank">8</a>], Nelson et al. envisioned the free-energy plot shown above as a graphic description of the kinetics of transition from monomeric Aβ to fibrillar Aβ (ΔG_formation). For the reverse reaction, Nelson et al. envision the ΔG_dissolution as the large free-energy barrier to spontaneous solubilization of amyloid fibrils. Presumably, it is this ΔG_dissolution that underlies the slow disappearance of brain plaques in the Borchelt study in transgenic mice.</p> <p>(Illustration: Sapna Khandwala, adapted from [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020417#pmed-0020417-b8" target="_blank">8</a>])</p></div

Arachidonic Acid Inhibits Basal sAPP_α Shedding but Has No Effect on holoAPP Levels

<div><p>(A) SweAPP cells were treated for 24 h with arachidonic acid (5 or 50 μM, represented by AA5 and AA50, respectively). Levels of sAPP_α were evaluated by immunoblot as described in Methods. C, control.</p> <p>(B) Graphic representation of data. Y-axis shows effect of treatment (in arbitrary units) divided by effect of untreated control (in arbitrary units); <i>n</i> = 6 independent experiments; *, <i>p</i> < 0.05 versus control; Student's <i>t</i> test.</p></div

Atorvastatin Activates sAPP_α Shedding Out of Proportion to Its Effect on holoAPP or csAPP

<div><p>(A) SweAPP N2a cells were treated with atorvastatin (Atv) for 24 h and then surface biotinylation was performed as described in Methods. Evaluation of csAPP was performed by immunoprecipitation–immunoblot after surface biotinylation, while holoAPP and sAPP_α were evaluated by immunoblot as described in Methods. C, control.</p> <p>(B) Graphic representation of data. Y-axis shows effect of treatment (in arbitrary units) divided by effect of untreated control (in arbitrary units); <i>n</i> = 3 independent experiments; *, <i>p</i> < 0.05; **, <i>p</i> < 0.01; Student's <i>t</i> test).</p></div

Simultaneous Treatment of SweAPP N2a Cells with a Statin and FTI-1 Causes Greater sAPP_α Shedding Than Either Drug Alone

<div><p>(A) SweAPP N2a cells were treated for 24 h with atorvastatin (Atv, 5 μM), simvastatin (Sim, 1 μM), FTI-1 (5 μM), or a combination of FTI-1 plus a statin. Levels of sAPP_α (top panel) or holoAPP (bottom panel) were evaluated as described in Methods. C, control.</p> <p>(B) Graphic representation of data. Y-axis shows effect of treatment (in arbitrary units) divided by effect of untreated control (in arbitrary units); <i>n</i> = 3 independent experiments; *, <i>p</i> < 0.05 versus control; **, <i>p</i> < 0.05 versus atorvastatin alone; ***, <i>p</i> < 0.05 versus simvastatin alone; Student's <i>t</i> test).</p></div

Isoprenoid Pathway and Sites of Action of Compounds Used in This Study

<p>FPP, farnesyl pyrophosphate; GGPP, geranylgeranyl pyrophosphate.</p

Structure and Expression of ROCK cDNAs, and Their Effect on Basal and Statin-Stimulated sAPP_α Shedding

<div><p>(A) Graphic representation of the ROCK1 constructs. Myc, Myc tag; KD, kinase domain; PH domain, pleckstrin homology domain; RBD, Rho-binding domain.</p> <p>(B) SweAPP N2a cells were transfected with GFP, CA ROCK1, or DN ROCK1 for 48 h. Cells were lysed and levels of expressed ROCK1 protein evaluated by immunoprecipitation–immunoblot as described in Methods.</p> <p>(C) Model for ROCK activity modulation by Rho.</p> <p>(D) SweAPP N2a cells were transfected for 48 h with control (GFP), CA ROCK1, or DN ROCK1 cDNAs. At the end of this incubation, cells were treated for an additional 24 h with simvastatin (Sim, 1 μM). sAPP_α and holoAPP were evaluated by immunoblot as described in Methods.</p> <p>(E) Graphic representation of data. Y-axis shows effect of treatment (in arbitrary units) divided by effect of untreated control (in arbitrary units); <i>n</i> = 3 independent experiments; *, <i>p</i> < 0.05 versus GFP; Student's <i>t</i> test). C, control.</p></div

Simultaneous Treatment of SweAPP N2a Cells with Statins and an Inhibitor of Endocytosis (PO) Yields More sAPP_α Shedding Than Does Treatment with Either Statins or PO Alone

<div><p>(A) SweAPP N2a cells were treated for 24 h with atorvastatin (Atv) or simvastatin (Sim) as indicated. Media were then replaced and cells were treated for an additional 20 min with atorvastatin, simvastatin, TNFα protease inhibitor, PO, or combinations, as indicated. Evaluation of sAPP_α and holoAPP was performed by Western blot as described in Methods. C, control.</p> <p>(B) Graphic representation of data. Y-axis shows effect of treatment (in arbitrary units) divided by effect of untreated control (in arbitrary units); <i>n</i> = 3 independent experiments; *, <i>p</i> < 0.05 versus control; **, <i>p</i> < 0.01 versus C; #, <i>p</i> < 0.05 versus atorvastatin alone; ##, <i>p</i> < 0.05 versus simvastatin alone; Student's <i>t</i> test).</p></div

Mevalonic Acid Reverses Statin-Induced, but Not FTI-1-Induced, sAPP_α Shedding

<p>SweAPP N2a cells were treated for 24 h with simvastatin (Sim, 1 μM), FTI-1 (5 μM), mevalonic acid (0–100 μM), or combinations as indicated. Levels of sAPP_α were evaluated by western blot as described in Methods. This figure is representative of the results of two independent experiments. C, control.</p

Raw data table for endogenous mouse brain Aβ40 and Aβ42 levels in mice exposed to nickel nanoparticles versus filtered air.

<p>Raw data of endogenous mouse brain Aβ40 and Aβ42 levels (pmol/L) in mice exposed to nickel nanoparticles (count median diameter 54 nm, at 1 mg/m³) (n = 16 per group) versus filtered air (n = 5 per group) for 3 hours in a nose-only exposure chamber. *Mouse 8 was excluded from the data analysis as these results were 2 SD's away from mean or closest value.</p