Dietetic Management of Irritable Bowel Syndrome: A National Survey of Dietary Approaches and Decision-making Factors.

Background And Aims: There has been a growing emphasis on dietary therapies for irritable bowel syndrome (IBS). Furthermore, there has been an evolving evidence base for the low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, gluten-free diet (GFD), and lactose-free diet. This study examines the dietary approaches employed and the factors influencing dietetic decision-making for IBS interventions.

Randomized trial in postprandial functional dyspepsia: Reassurance and diagnostic explanation with or without traditional dietary advice.

Background: Almost 80% of individuals with functional dyspepsia experience meal-related symptoms and are diagnosed with postprandial distress syndrome (PDS). However, studies evaluating dietary modifications in PDS are sparse. We performed a single-center randomized trial comparing reassurance and diagnostic explanation (RADE) with or without traditional dietary advice (TDA) in PDS.

A Three-Step Method for the Preparation of -Substituted 3,4-Dihydroisoquinolin-1(2)-ones and Heteroaryl-Fused 3,4-Dihydropyridin-2(1)-ones from 2-Bromobenzoate Precursors.

We demonstrate a general method for the preparation of diverse -substituted 3,4-dihydroisoquinolin-1(2)-one compounds through an overall three-step cross-coupling/cyclization/-deprotection/-alkylation sequence. In the first step, ethyl 2-bromobenzoates and 2-bromo-1-carboxyethyl heterocycles are cross-coupled with commercially available potassium (2-((-butoxycarbonyl)amino)ethyl)trifluoroborate to produce (hetero)aryl-substituted 3-[(-Boc-2-carboxyethyl)phenyl]ethylamines. In a subsequent two-stage process, these (hetero)arylethylamines undergo base-mediated ring closure followed by -deprotection and -alkylation to produce -substituted 3,4-dihydroisoquinolin-1(2)-ones and heteroaryl-fused -benzyl 3,4-dihydropyridin-2(1)-ones.

Diet and irritable bowel syndrome: an update from a UK consensus meeting.

There has been a renewed interest in the role of dietary therapies to manage irritable bowel syndrome (IBS), with diet high on the agenda for patients. Currently, interest has focussed on the use of traditional dietary advice (TDA), a gluten-free diet (GFD) and the low FODMAP diet (LFD). A consensus meeting was held to assess the role of these dietary therapies in IBS, in Sheffield, United Kingdom.

Efficacy and Acceptability of Dietary Therapies in Non-Constipated Irritable Bowel Syndrome: A Randomized Trial of Traditional Dietary Advice, the Low FODMAP Diet, and the Gluten-Free Diet.

Background & Aims: Various diets are proposed as first-line therapies for non-constipated irritable bowel syndrome (IBS) despite insufficient or low-quality evidence. We performed a randomized trial comparing traditional dietary advice (TDA) against the low FODMAP diet (LFD) and gluten-free diet (GFD).

Methods: Patients with Rome IV-defined non-constipated IBS were randomized to TDA, LFD, or GFD (the latter allowing for minute gluten cross-contamination).

Is Roux-en-Y Feeding Jejunostomy a Safe and Effective Operation in Children? A Systematic Review Exploring Outcomes.

Objectives: Roux-en-Y jejunostomy (REYJ) may establish feeding in children with foregut dysmotility or severe gastro-esophageal reflux disease (GERD). Nevertheless, concerns have been raised about safety and efficacy. We, therefore, evaluated outcomes of REYJ by systematic review to determine if this was a satisfactory option for achieving enteral autonomy in children with complex nutritional needs.

The low FODMAP diet for IBS; A multicentre UK study assessing long term follow up.

Background: The low FODMAP diet (LFD) is effective in managing irritable bowel syndrome (IBS) in the short term. This study assessed the long-term effect of the LFD on symptoms, nutritional composition and socialising.

Methods: Patients with IBS who received dietetic-led LFD advice were approached at long term follow up (>6 months post LFD advice) from six centres across the United Kingdom.

Design and synthesis of novel methoxypyridine-derived gamma-secretase modulators.

The evolution of gamma-secretase modulators (GSMs) through the introduction of novel heterocycles with the goal of aligning activity for reducing the levels of Aβ42 and properties consistent with a drug-like molecule are described. The insertion of a methoxypyridine motif within the tetracyclic scaffold provided compounds with improved activity for arresting Aβ42 production as well as improved properties, including solubility. In vivo pharmacokinetic analysis demonstrated that several compounds within the novel series were capable of crossing the BBB and accessing the therapeutic target.

Hurricane Harvey Aftermath.

Natural disasters, such as hurricanes and severe flooding, pose a threat of increased skin and soft-tissue infections, especially in the event of open fractures and wading through the waters. The purpose of this case study is to present a complex patient sustaining trauma resulting in an open bimalleolar fracture, multiple wounds, and exposure to a variety of water-borne pathogens during Hurricane Harvey in Houston, Texas, in 2017. He underwent multiple incision and drainage procedures, tissue cultures, and placement of antibiotic beads, with an application of external fixation to the left ankle.

National survey evaluating the provision of gastroenterology dietetic services in England.

Aims: The aim of the study was to assess the provision of dietetic services for coeliac disease (CD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD).

Methods: Hospitals within all National Health Service trusts in England were approached (n=209). A custom-designed web-based questionnaire was circulated via contact methods of email, post or telephone.

Optimized plant compound with potent anti-biofilm activity across gram-negative species.

Many human diseases, including cystic fibrosis lung infections, are caused or exacerbated by bacterial biofilms. Specialized modes of motility, including swarming and twitching, allow gram-negative bacteria to spread across surfaces and form biofilms. Compounds that inhibit these motilities could slow the spread of biofilms, thereby allowing antibiotics to work better.

A Gluten Reduction Is the Patients' Choice for a Dietary 'Bottom Up' Approach in IBS-A Comment on "A 5Ad Dietary Protocol for Functional Bowel Disorders" 2019, , 1938.

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To start or not: Factors to consider when implementing routine probiotic use in the NICU.

Supplementation of probiotics to very low birth weight (VLBW) infants has been extensively studied, with multiple meta-analyses reporting probiotics decrease the risk of necrotizing enterocolitis (NEC) and death. Despite availability of this evidence, the decision to initiate routine probiotic supplementation to preterm infants continues to be a complex one. There are uncertainties regarding the use of probiotics, including selecting the appropriate product, dose and target population.

Science-based assessment of source materials for cell-based medicines: report of a stakeholders workshop.

Human pluripotent stem cells (hPSCs) have the potential to transform medicine. However, hurdles remain to ensure safety for such cellular products. Science-based understanding of the requirements for source materials is required as are appropriate materials.

Leadership and management in UK medical school curricula.

Purpose Although medical leadership and management (MLM) is increasingly being recognised as important to improving healthcare outcomes, little is understood about current training of medical students in MLM skills and behaviours in the UK. The paper aims to discuss these issues. Design/methodology/approach This qualitative study used validated structured interviews with expert faculty members from medical schools across the UK to ascertain MLM framework integration, teaching methods employed, evaluation methods and barriers to improvement.

Synthesis and Biological Evaluation of N-((1-(4-(Sulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide Inhibitors of Glycine Transporter-1.

We previously disclosed the discovery of rationally designed N-((1-(4-(propylsulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide inhibitors of glycine transporter-1 (GlyT-1), represented by analogues 10 and 11. We describe herein further structure-activity relationship exploration of this series via an optimization strategy that primarily focused on the sulfonamide and benzamide appendages of the scaffold. These efforts led to the identification of advanced leads possessing a desirable balance of excellent in vitro GlyT-1 potency and selectivity, favorable ADME and in vitro pharmacological profiles, and suitable pharmacokinetic and safety characteristics.

Design and synthesis of aminothiazole modulators of the gamma-secretase enzyme.

The design and construction of a series of novel aminothiazole-derived γ-secretase modulators is described. The incorporation of heterocyclic replacements of the terminal phenyl D-ring of lead compound 1 was conducted in order to align potency with favorable drug-like properties. γ-Secretase modulator 28 displayed good activity for in vitro inhibition of Aβ42, as well as substantial improvement in ADME and physicochemical properties, including aqueous solubility.

Discovery of silyl proline containing HCV NS5A inhibitors with pan-genotype activity: SAR development.

HCV NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays thus making them attractive components for inclusion in an all oral fixed dose combination treatment regimen. Herein we describe the research efforts that led to the discovery of silyl proline containing HCV NS5A inhibitors such as 7e and 8a with pan-genotype activity profile and acceptable pharmacokinetic properties.

Inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) reduces neonatal hypoxic-ischaemic brain damage.

Hypoxic-ischaemic encephalopathy is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy and cognitive disabilities. Hypoxia-ischaemia (HI) strongly up-regulates Signal Transducer and Activator of Transcription 3 (STAT3) in the immature brain. Our aim was to establish whether STAT3 up-regulation is associated with neonatal HI-brain damage and evaluate the phosphorylated STAT3-contribution from different cell types in eliciting damage.

Combined in vivo multiphoton and CARS imaging of healthy and disease-affected human skin.

We present combined epi-coherent anti-Stokes Raman scattering (CARS) and multiphoton imaging with both chemical discrimination and subcellular resolution on human skin in vivo. The combination of both image modalities enables label-free imaging of the autofluorescence of endogenous fluorophores by two-photon excited fluorescence, as well as imaging of the distribution of intercellular lipids, topically applied substances and water by CARS. As an example for medical imaging, we investigated healthy and psoriasis-affected human skin with both image modalities in vivo and found indications for different lipid distributions on the cellular level.

Clinical study on the effects of a cosmetic product on dermal extracellular matrix components using a high-resolution multiphoton tomograph.

Background/purpose: The aim of this study was to demonstrate the effects of selected plant extracts in a cosmetic cream on the dermal network components after a 3-month treatment using an in vivo multiphoton tomographic device.

Methods: Twenty-four Caucasian women aged between 45 and 65 applied randomly a cosmetic emulsion B containing active ingredients (soy and jasmine) twice a day on one arm and its vehicle A (without active ingredients) on the other arm during 3 months. Measurements were performed on the internal side of the forearm before starting the treatment (T0), after 4 week (T4) and 12 weeks (T12) treatment.