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.Evidence for TDA is from case control studies and clinical experience. Randomised controlled trials (RCT) have demonstrated the benefit of soluble fibre in IBS. No studies have assessed TDA in comparison to a habitual or sham diet. There have been a number of RCTs demonstrating the efficacy of a GFD at short-term follow-up, with a lack of long-term outcomes. Whilst gluten may lead to symptom generation in IBS, other components of wheat may also play an important role, with recent interest in the role of fructans, wheat germ agglutinins, as well as alpha amylase trypsin inhibitors. There is good evidence for the use of a LFD at short-term follow-up, with emerging evidence demonstrating its efficacy at long-term follow-up. There is overlap between the LFD and GFD with IBS patients self-initiating gluten or wheat reduction as part of their LFD. Currently, there is a lack of evidence to suggest superiority of one diet over another, although TDA is more acceptable to patients.In view of this evidence, our consensus group recommends that dietary therapies for IBS should be offered by dietitians who first assess dietary triggers and then tailor the intervention according to patient choice. Given the lack of dietetic services, novel approaches such as employing group clinics and online webinars may maximise capacity and accessibility for patients. Further research is also required to assess the comparative efficacy of dietary therapies to other management strategies available to manage IBS.

Activity Levels and Outcomes of a Standalone Regional Paediatric High Dependency Unit.

Aim The Paediatric High Dependency Unit (PHDU) at University Hospital Limerick (UHL) operates as the only standalone unit outside of Dublin centres. The aim of this study was to describe a regional PHDU population, compare outcomes with international standards (PICANet) and ensure adequate clinical governance. Methods This is a retrospective analysis of 126 admission records from January - December 2019. Results There were 126 admissions to PHDU in 2019, of which respiratory (n=81, 64.3%) and neurological (n=23, 18.3%) subgroups represented the largest populations. Median length of stay was two days with mean age of admission 3.97 ± 4.5 years and slightly more male admissions (56%). Of the total, 65% required oxygen, 32.1% needed CPAP directly and 38% commenced high-flow, of whom 29% transitioned to CPAP. Transfer for tertiary care was required in 10.3%, of whom 7.9% needed PICU. Conclusion The data show UHL PHDU to have a patient population reflecting international trends as well as producing satisfactory patient outcomes. With a low rate of transfer for tertiary care and given that 15 other paediatric units exist in the Republic of Ireland outside Dublin, development of regional PHDU capacity would provide great opportunity to decrease strain on PICU bed capacity, particularly during busy Winter months.

Impact of shear rate pattern on post-occlusive near-infrared spectroscopy microvascular reactivity.

The primary aim of the present study was to determine the impact of acute changes in shear rate patterns, in particular retrograde shear rate, on microvascular function in 15 healthy, young men and women as determined via the post-occlusive near-infrared spectroscopy (NIRS) microvascular reactivity response. Microvascular reactivity, via NIRS-derived measurements of post-occlusion tissue saturation index (TSI%) and total microvascular hemoglobin+myoglobin concentration ([Hb]total), were assessed in each participant before and immediately after exposure to a 30min retrograde shear treatment. Retrograde shear was achieved via a blood pressure cuff placed below the knee inflated to 75mmHg. One leg was exposed to the retrograde shear (Treatment leg) and the contralateral leg served as a non-treatment control. In the Treatment leg, significant increases in retrograde shear rate occurred during the retrograde intervention. Following the intervention, the area under the TSI% post-occlusion response curve, which represents the total microvascular reactivity response, and the absolute peak TSI% response were significantly increased compared to pre-intervention in the Treatment leg, but not the Control leg. The absolute peak [Hb]total response was significantly increased post-intervention in both legs. These results are in contrast to our hypothesis that 75mmHg cuff inflation, designed to increase retrograde shear rate in the femoral artery would negatively affect post-occlusive microvascular reactivity. These data suggest that the current method of increasing retrograde shear rate in the intact human does not adversely impact NIRS derived measurements of microvascular reactivity.

A tidally distorted dwarf galaxy near NGC 4449.

NGC 4449 is a nearby Magellanic irregular starburst galaxy with a B-band absolute magnitude of -18 and a prominent, massive, intermediate-age nucleus at a distance from Earth of 3.8 megaparsecs (ref. 3). It is wreathed in an extraordinary neutral hydrogen (H I) complex, which includes rings, shells and a counter-rotating core, spanning ∼90 kiloparsecs (kpc; refs 1, 4). NGC 4449 is relatively isolated, although an interaction with its nearest known companion--the galaxy DDO 125, some 40 kpc to the south--has been proposed as being responsible for the complexity of its H I structure. Here we report the presence of a dwarf galaxy companion to NGC 4449, namely NGC 4449B. This companion has a V-band absolute magnitude of -13.4 and a half-light radius of 2.7 kpc, with a full extent of around 8 kpc. It is in a transient stage of tidal disruption, similar to that of the Sagittarius dwarf near the Milky Way. NGC 4449B exhibits a striking S-shaped morphology that has been predicted for disrupting galaxies but has hitherto been seen only in a dissolving globular cluster. We also detect an additional arc or disk ripple embedded in a two-component stellar halo, including a component extending twice as far as previously known, to about 20 kpc from the galaxy's centre.

Oxidative stress in major depressive and anxiety disorders, and the association with antidepressant use; results from a large adult cohort.

BACKGROUND: Oxidative stress has been implicated in the pathophysiology of major depressive disorder (MDD) and anxiety disorders and may be influenced by antidepressant use. This study investigated the association of oxidative stress, measured by plasma levels of F2-isoprostanes and 8-hydroxy-2'-deoxyguanosine (8-OHdG) reflecting oxidative lipid and DNA damage respectively, with MDD, anxiety disorders and antidepressant use in a large cohort. METHOD: Data was derived from the Netherlands Study of Depression and Anxiety including patients with current (N = 1619) or remitted (N = 610) MDD and/or anxiety disorder(s) (of which N = 704 antidepressant users) and 612 controls. Diagnoses were established with the Composite International Diagnostic Interview. Plasma 8-OHdG and F2-isoprostanes were measured using LC-MS/MS. ANCOVA was performed adjusted for sampling, sociodemographic, health and lifestyle variables. RESULTS: F2-isoprostanes did not differ between controls and patients, or by antidepressant use. Patients with current disorders had lower 8-OHdG (mean 42.1 pmol/l, 95% CI 40.4-43.8) compared to controls (45.0 pmol/l, 95% CI 42.9-47.2; p < 0.001) after adjustment for sampling, sociodemographics and lifestyle, but these differences disappeared after further adjustment for antidepressant use (p = 0.562). Antidepressant users had lower 8-OHdG levels (38.2 pmol/l, 95% CI 36.5-39.9) compared to controls (44.9 pmol/l, 95% CI 43.2-46.6; Cohen's d = 0.21, p < 0.001). Results for 8-OHdG were comparable across disorders (MDD and/or anxiety disorders), and all antidepressant types (SSRIs, TCAs, other antidepressants). CONCLUSION: Contrary to previous findings this large-scale study found no increased oxidative stress in MDD and anxiety disorders. Antidepressant use was associated with lower oxidative DNA damage, suggesting antidepressants may have antioxidant effects.

Prevalence of blood donor iron deficiency and feasibility ferritin-based iron replacement: a blood collection agency-based study.

Iron depletion is high in frequent whole-blood donors. It is of interest to blood centres to develop ways to mitigate this risk while maintaining the current blood supply. Our feasibility study shows that blood collection agencies can measure iron stores and safely offer iron replacement in frequent blood donors with low ferritin to reduce the risk of iron depletion and future donor deferrals for low haemoglobin.

Metabolic monitoring in the intensive care unit: a comparison of the Medgraphics Ultima, Deltatrac II, and Douglas bag collection methods.

BACKGROUND: The accuracy of oxygen consumption measurement by indirect calorimeters is poorly validated in mechanically ventilated intensive care patients where multiple confounders exist. This study sought to compare the Medgraphics Ultima (MGU) and Deltatrac II (DTII) devices, and the Douglas bag (DB) technique in mechanically ventilated patients at rest. METHODS: Prospective comparison of oxygen consumption measurement using three indirect calorimetry techniques in stable, resting mechanically ventilated patients at rest. Oxygen consumption (VO2), carbon dioxide production (VCO2), resting energy expenditure (REE), and respiratory quotient (RQ) were recorded breath-by-breath by the MGU over a 30-75 min period. During this time, simultaneous measurements were taken using the DTII, the DB, or both. RESULTS: While there was no systematic error (bias) between measurements made by the three techniques (VO2: MGU vs DTII 3.6%, MGU vs DB 3.3%), the limits of agreement were wide (VO2: MGU vs DTII 33%, MGU vs DB 54%). CONCLUSIONS: Resting oxygen consumption values in stable mechanically ventilated patients measured by the three techniques showed acceptable bias but poor precision. There is an important clinical and research need to develop new indirect calorimeters specifically tailored to measure oxygen consumption during mechanical ventilation.

Comparing physiological impacts of positive pressure ventilation versus self-breathing via a versatile cardiopulmonary model incorporating a novel alveoli opening mechanism.

Mathematical models can be used to generate high-fidelity simulations of the cardiopulmonary system. Such models, when applied to real patients, can provide valuable insights into underlying physiological processes that are hard for clinicians to observe directly. In this work, we propose a novel modelling strategy capable of generating scenario-specific cardiopulmonary simulations to replicate the vital physiological signals clinicians use to determine the state of a patient. This model is composed of a tree-like pulmonary system that features a novel, non-linear alveoli opening strategy, based on the dynamics of balloon inflation, that interacts with the cardiovascular system via the thorax. A baseline simulation of the model is performed to measure the response of the system during spontaneous breathing which is subsequently compared to the same system under mechanical ventilation. To test the new lung opening mechanics and systematic recruitment of alveolar units, a positive end-expiratory pressure (PEEP) test is performed and its results are then compared to simulations of a deep spontaneous breath. The system displays a marked decrease in tidal volume as PEEP increases, replicating a sigmoidal curve relationship between volume and pressure. At high PEEP, cardiovascular function is shown to be visibly impaired, in contrast to the deep breath test where normal function is maintained.

Multilocus sequence typing for characterization of Staphylococcus pseudintermedius.

Staphylococcus pseudintermedius is an opportunistic pathogen in dogs. Four housekeeping genes with allelic polymorphisms were identified and used to develop an expanded multilocus sequence typing (MLST) scheme. The new seven-locus technique shows S. pseudintermedius to have greater genetic diversity than previous methods and discriminates more isolates based upon host origin.

Molecular architecture of the ciliary tip revealed by cryo-electron tomography.

Cilia are essential organelles that protrude from the cell body. Cilia are made of a microtubule-based structure called the axoneme. In most types of cilia, the ciliary tip is distinct from the rest of the cilium. Here, we used cryo-electron tomography and subtomogram averaging to obtain the structure of the ciliary tip of the ciliate Tetrahymena thermophila. We show the microtubules in the tip are highly cross-linked with each other and stabilised by luminal proteins, plugs and cap proteins at the plus ends. In the tip region, the central pair lacks the typical projections and twists significantly. By analysing cells lacking a ciliary tip-enriched protein CEP104/FAP256 by cryo-electron tomography and proteomics, we discovered candidates for the central pair cap complex and explain potential functions of CEP104/FAP256. These data provide new insights into the function of the ciliary tip and inform about the mechanisms of ciliary assembly and length regulation.

Evaluation of gene modification strategies for the development of low-alcohol-wine yeasts.

Saccharomyces cerevisiae has evolved a highly efficient strategy for energy generation which maximizes ATP energy production from sugar. This adaptation enables efficient energy generation under anaerobic conditions and limits competition from other microorganisms by producing toxic metabolites, such as ethanol and CO(2). Yeast fermentative and flavor capacity forms the biotechnological basis of a wide range of alcohol-containing beverages. Largely as a result of consumer demand for improved flavor, the alcohol content of some beverages like wine has increased. However, a global trend has recently emerged toward lowering the ethanol content of alcoholic beverages. One option for decreasing ethanol concentration is to use yeast strains able to divert some carbon away from ethanol production. In the case of wine, we have generated and evaluated a large number of gene modifications that were predicted, or known, to impact ethanol formation. Using the same yeast genetic background, 41 modifications were assessed. Enhancing glycerol production by increasing expression of the glyceraldehyde-3-phosphate dehydrogenase gene, GPD1, was the most efficient strategy to lower ethanol concentration. However, additional modifications were needed to avoid negatively affecting wine quality. Two strains carrying several stable, chromosomally integrated modifications showed significantly lower ethanol production in fermenting grape juice. Strain AWRI2531 was able to decrease ethanol concentrations from 15.6% (vol/vol) to 13.2% (vol/vol), whereas AWRI2532 lowered ethanol content from 15.6% (vol/vol) to 12% (vol/vol) in both Chardonnay and Cabernet Sauvignon juices. Both strains, however, produced high concentrations of acetaldehyde and acetoin, which negatively affect wine flavor. Further modifications of these strains allowed reduction of these metabolites.

Traumatic wound microbiome workshop.

On May 9-10, 2011, the Walter Reed Army Institute of Research, as the Army Center of Excellence for Infectious Disease, assembled over a dozen leaders in areas related to research into the communities of microorganisms which colonize and infect traumatic wounds. The objectives of the workshop were to obtain guidance for government researchers, to spur research community involvement in the field of traumatic wound research informed by a microbiome perspective, and to spark collaborative efforts serving the Wounded Warriors and similarly wounded civilians. During the discussions, it was made clear that the complexity of these infections will only be met by developing a new art of clinical practice that engages the numerous microbes and their ecology. It requires the support of dedicated laboratories and technologists who advance research methods such as community sequencing, as well as the kinds of data analysis expertise and facilities. These strategies already appear to be bearing fruit in the clinical management of chronic wounds. There are now funding announcements and programs supporting this area of research open to extramural collaborators.

Low levels of food involvement and negative affect reduce the quality of diet in women of lower educational attainment.

BACKGROUND: Women of lower educational attainment tend to have poorer quality diets and lower food involvement (an indicator of the priority given to food) than women of higher educational attainment. The present study reports a study of the role of food involvement in the relationship between educational attainment and quality of diet in young women. METHODS: The first phase uses six focus group discussions (n = 28) to explore the function of food involvement in shaping the food choices of women of lower and higher educational attainment with young children. The second phase is a survey that examines the relationship between educational attainment and quality of diet in women, and explores the role of mediating factors identified by the focus group discussions. RESULTS: The focus groups suggested that lower food involvement in women of lower educational attainment might be associated with negative affect (i.e. an observable expression of negative emotion), and that this might mean that they did not place a high priority on eating a good quality diet. In support of this hypothesis, the survey of 1010 UK women found that 14% of the effect of educational attainment on food involvement was mediated through the woman's affect (P ≤ 0.001), and that 9% of the effect of educational attainment on quality of diet was mediated through food involvement (P ≤ 0.001). CONCLUSIONS: Women who leave school with fewer qualifications may have poorer quality diets than women with more qualifications because they tend to have a lower level of food involvement, partly attributed to a more negative affect. Interventions to improve women's mood may benefit their quality of diet.

Equity and efficiency: striving for a solution for the introduction of new medicines.

The aim of this study was to describe the evolution of mechanisms to manage the introduction of new medicines and their impact on the health-care system in Scotland. The study was a review of published and unpublished national audits and surveys on the introduction of new medicines in Scotland. Before the Scottish Medicines Consortium (SMC) was established, Area Drug and Therapeutics Committees (ADTCs) played a key role in advising National Health Service (NHS) Boards in Scotland on the use of new medicines. There was evidence of variation in the medicines evaluated and, in some cases, the evidence used leading to different decisions for the same medicine. After the SMC was established, ADTC decisions had become more consistent and comprehensive. The role of ADTCs evolved from evaluation of medicines to assessment of local implications and implementation of SMC advice. There was increased recognition of the importance of monitoring medicine use. This review demonstrated a clear evolution in the evaluation and implementation of new medicines by ADTCs across NHS Scotland. After the SMC was established, more medicines were considered by ADTCs and there was greater consistency in those considered for local implementation. ADTCs have moved from evaluation of new medicines to other aspects of medicine management, including assessment of local implications and implementation of SMC advice.

Anaesthesia management of a child with aromatic L-amino acid decarboxylase deficiency.

Aromatic L-amino acid decarboxylase deficiency is an autosomal recessive disorder that results in a lack of neurotransmitters including serotonin, dopamine, noradrenaline and adrenaline. It is characterised by developmental delay, severe hypotonia and autonomic disturbance. In patients with this condition, catecholamine deficiency and autonomic dysfunction, resulting in haemodynamic instability under anaesthesia is a primary concern. There is increased sensitivity to exogenous catecholamines and indirect acting agents, such as ephedrine, are ineffective. Hypoglycaemia, difficult airway status and drug interactions such as with monoamine oxidase inhibitors are also of concern, and these patients are at risk of dystonic crises peri-operatively. A 6-year-old boy with aromatic L-amino acid decarboxylase deficiency presented for gastrointestinal endoscopy. Following multidisciplinary discussion, we elected to provide general anaesthesia with a propofol target-controlled infusion, which proceeded without incident. In this report, we describe the precautions taken in this case, and discuss the provision of general anaesthesia for children with rare neurometabolic disorders.

Increased epithelial permeability in pulmonary fibrosis in relation to disease progression.

Epithelial injury contributes to pathogenesis in idiopathic pulmonary fibrosis (IPF) but its role in the interstitial lung disease (ILD) of systemic sclerosis (SSc) is uncertain. We quantified the prognostic significance of inhaled technetium-99m ((99m)Tc)-labelled diethylene triamine pentacetate (DTPA) pulmonary clearance, a marker of the extent of epithelial injury, in both diseases. Baseline (99m)Tc-DTPA pulmonary clearance was evaluated retrospectively in patients with SSc-ILD (n = 168) and IPF (n = 97) against mortality and disease progression. In SSc-ILD, the rapidity of total clearance (hazard ratio (HR) 1.02, 95% CI 1.01-1.03; p = 0.001) and the presence of abnormally rapid clearance (HR 2.10; 95% CI 1.25-3.53; p = 0.005) predicted a shorter time to forced vital capcity (FVC) decline, independent of disease severity. These associations were robust in both mild and severe disease. By contrast, in IPF, delayed clearance of the slow component, an expected consequence of honeycomb change, was an independent predictor of a shorter time to FVC decline (HR 1.01, 95% CI 1.00-1.02; p<0.01). Epithelial injury should be incorporated in pathogenetic models in SSc-ILD. By contrast, outcome is not linked to the overall extent of epithelial injury in IPF, apart from abnormalities ascribable to honeycombing, suggesting that core pathogenetic events may be more spatially focal in that disease.

Randomized, prospective, placebo-controlled trial of bosentan in interstitial lung disease secondary to systemic sclerosis.

OBJECTIVE: Endothelin is implicated as a participatory pathway in systemic sclerosis (SSc). We tested this hypothesis in a 12-month trial of bosentan, a nonselective endothelin receptor antagonist, as a therapy for SSc-related interstitial lung disease (ILD). METHOD: Patients with SSc and significant ILD were recruited to this prospective, double-blind, randomized, placebo-controlled, parallel group study. The inclusion criteria were designed to select a cohort enriched for patients with active and progressive disease. Exclusion factors included significant pulmonary hypertension. Patients with a diffusing capacity for carbon monoxide of <80% predicted and a 6-minute walk distance of 150-500 meters or a 6-minute walk distance of > or = 500 meters with a decrease in oxygen saturation received bosentan or placebo. The primary efficacy end point was a change in the 6-minute walk distance from baseline up to month 12. Secondary end points included time to death or worsening results of pulmonary function tests (PFTs). The safety and tolerability of bosentan were also assessed. RESULTS: Among the 163 patients, 77 were randomized to receive bosentan, and 86 were randomized to receive placebo. No significant difference between treatment groups was observed for change in the 6-minute walk distance up to month 12. No deaths occurred in this study group. Forced vital capacity and diffusing capacity for carbon monoxide remained stable in the majority of patients in both groups. Significant worsening of PFT results occurred in 25.6% of patients receiving placebo and 22.5% of those receiving bosentan (P not significant). CONCLUSION: No improvement in exercise capacity was observed in the bosentan-treated group compared with the placebo group, and no significant treatment effect was observed for the other end points. Although many outcome variables were stable, bosentan did not reduce the frequency of clinically important worsening. These data do not support the use of endothelin receptor antagonists as therapy for ILD secondary to SSc.

Patent ductus arteriosus repair in general practice.

A 3-month-old female German Shepherd puppy was presented for routine vaccination. Clinical evaluation revealed a grade 5/6 continuous murmur with the point of maximal intensity over the left 4th intercostal space. Echocardiography revealed a patent ductus arteriosus (PDA). The PDA was closed by a team of general practitioners using the Jackson-Henderson technique, via a standard 4th intercostal thoracotomy. A multi-modal approach to analgesia and premedication was employed. A successful outcome was achieved with no murmur or evidence of cardiac disease present 6 months after surgical occlusion. The literature is reviewed with an emphasis placed on choosing techniques that are appropriate to the level of expertise of the surgical and anaesthetic teams, as well as the surgical facilities available.

Co-infection of macrophages modulates interferon gamma and tumor necrosis factor-induced activation against intracellular pathogens.

Co-infection of macrophages (M phi) with Toxoplasma gondii and Mycobacterium avium-intracellulare complex (MAC) has been observed in patients with acquired immunodeficiency syndrome (AIDS). In this study we have demonstrated that co-infected murine M phi respond differently to cytokine stimulation than M phi infected with either of the microorganisms alone. Whereas treatment with interferon gamma (IFN-gamma) activated both single and co-infected groups of M phi to kill T. gondii, treatment with TNF did not influence the rate of MAC growth in co-infected M phi, in contrast with the inhibition of growth observed in MAC-infected M phi. These results suggest that in AIDS patients suffering infection with multiple intracellular pathogens, the ability of cytokines to stimulate microbicidal or static activity in mononuclear phagocytes can be impaired by the presence of more than one of the intracellular organisms.