'What research was carried out on this vaginal mesh?' Health-related concerns in women following mesh-augmented prolapse surgery: a thematic analysis.

OBJECTIVE: To understand health-related issues in women following mesh-augmented prolapse surgery. DESIGN: Inductive thematic analysis of free-text comments from participants in a cross-sectional study of laparoscopic mesh sacrohysteropexy. SETTING: Tertiary urogynaecology centres, United Kingdom. POPULATION: Women who underwent laparoscopic mesh sacrohysteropexy by surgeons based at two tertiary urogynaecology centres between 2010 and 2018. METHODS: A total of 1766 potential participants were contacted by post and invited to complete paper, online or telephone questionnaires containing a free-text comments section. Of 1121 participants (response proportion 63.5%), 752 (67.1%) provided such comments. These were analysed with a six-stage inductive thematic analysis, using NVivo 11® software. MAIN OUTCOME MEASURES: Themes developed from free-text comments. RESULTS: Following familiarisation, 29 codes and 189 sub-codes were identified. These defined six themes: pelvic floor symptoms, health status, treatment success, mesh, pain and care received. The majority of comments centred on the first of these six themes. There were concerns about mesh use and a desire for more information. A range of pain symptoms were mentioned, often associated with pelvic floor symptoms, prolapse surgery or mesh. CONCLUSIONS: Despite the mesh controversy, pelvic floor symptoms and their impact on quality of life remain the principle concern of women following mesh-augmented prolapse surgery. There is a need for quality, accessible and evidence-based information sources for those women with concerns, and for those considering such surgery in the future, particularly regarding mesh safety and postoperative recovery. The relationships between pain, prolapse, mesh and pelvic floor surgery require further study. TWEETABLE ABSTRACT: Following mesh-augmented prolapse surgery, pelvic floor symptoms remain women's main focus; pain deserves further research.

Possible control of acute outbreaks of a marine fungal pathogen by nominally herbivorous tropical reef fish.

Primary producers in terrestrial and marine systems can be affected by fungal pathogens threatening the provision of critical ecosystem services. Crustose coralline algae (CCA) are ecologically important members of tropical reef systems and are impacted by coralline fungal disease (CFD) which manifests as overgrowth of the CCA crust by fungal lesions causing partial to complete mortality of the CCA host. No natural controls for CFD have been identified, but nominally herbivorous fish could play a role by consuming pathogenic fungi. We documented preferential grazing on fungal lesions by adults of six common reef-dwelling species of herbivorous Acanthuridae and Labridae, (surgeonfish and parrotfish) which collectively demonstrated an ~ 80-fold higher grazing rate on fungal lesions relative to their proportionate benthic coverage, and a preference for lesions over other palatable substrata (e.g. live scleractinian coral, CCA, or algae). Furthermore, we recorded a ~ 600% increase in live CFD lesion size over an approximately 2-week period when grazing by herbivorous fish was experimentally excluded suggesting that herbivorous reef fish could control CFD progression by directly reducing biomass of the fungal pathogen. Removal rates may be sufficient to allow CCA to recover from infection and explain historically observed natural waning behaviour after an outbreak. Thus, in addition to their well-known role as determinants of macroalgal overgrowth of reefs, herbivorous fish could thus also be important in control of diseases affecting crustose coralline algae that stabilize the foundation of coral reef substrata.

Observation of magnetic vortex pairs at room temperature in a planar α-Fe2O3/Co heterostructure.

Vortices, occurring whenever a flow field 'whirls' around a one-dimensional core, are among the simplest topological structures, ubiquitous to many branches of physics. In the crystalline state, vortex formation is rare, since it is generally hampered by long-range interactions: in ferroic materials (ferromagnetic and ferroelectric), vortices are observed only when the effects of the dipole-dipole interaction are modified by confinement at the nanoscale1-3, or when the parameter associated with the vorticity does not couple directly with strain 4 . Here, we observe an unprecedented form of vortices in antiferromagnetic haematite (α-Fe2O3) epitaxial films, in which the primary whirling parameter is the staggered magnetization. Remarkably, ferromagnetic topological objects with the same vorticity and winding number as the α-Fe2O3 vortices are imprinted onto an ultra-thin Co ferromagnetic over-layer by interfacial exchange. Our data suggest that the ferromagnetic vortices may be merons (half-skyrmions, carrying an out-of plane core magnetization), and indicate that the vortex/meron pairs can be manipulated by the application of an in-plane magnetic field, giving rise to large-scale vortex-antivortex annihilation.

Predicting estrogen receptor binding of chemicals using a suite of in silico methods - Complementary approaches of (Q)SAR, molecular docking and molecular dynamics.

With the aim of obtaining reliable estimates of Estrogen Receptor (ER) binding for diverse classes of compounds, a weight of evidence approach using estimates from a suite of in silico models was assessed. The predictivity of a simple Majority Consensus of (Q)SAR models was assessed using a test set of compounds with experimental Relative Binding Affinity (RBA) data. Molecular docking was also carried out and the binding energies of these compounds to the ERα receptor were determined. For a few selected compounds, including a known full agonist and antagonist, the intrinsic activity was determined using low-mode molecular dynamics methods. Individual (Q)SAR model predictivity varied, as expected, with some models showing high sensitivity, others higher specificity. However, the Majority Consensus (Q)SAR prediction showed a high accuracy and reasonably balanced sensitivity and specificity. Molecular docking provided quantitative information on strength of binding to the ERα receptor. For the 50 highest binding affinity compounds with positive RBA experimental values, just 5 of them were predicted to be non-binders by the Majority QSAR Consensus. Furthermore, agonist-specific assay experimental values for these 5 compounds were negative, which indicates that they may be ER antagonists. We also showed different scenarios of combining (Q)SAR results with Molecular docking classification of ER binding based on cut-off values of binding energies, providing a rational combined strategy to maximize terms of toxicological interest.

The "Risser+" grade: a new grading system to classify skeletal maturity in idiopathic scoliosis.

PURPOSE: This study aims to propose and validate a new unified "Risser+" grade that combines the North American (NA) and European (EU) variants of the classic Risser score. The "Risser+ " grade can effectively combine the North American and European Risser Classifications for skeletal maturity with adequate intra-rater/inter-rater reliability and agreement. METHODS: Agreement and reliability were evaluated for 6 raters (3-NA, 3-EU) who assessed 120 pelvic radiographs from the BrAIST trial, all female, average age 13.4 (range 10.1-16.5 years). Blinded raters reviewed x-rays at two time-points. Intra- and inter-rater agreement (RA) were established with Krippendorff's alpha (k-alpha), while intra- and inter-rater reliability (RR) were established with intraclass correlation coefficients (ICC). Acceptable agreement and reliability were set a priori at 0.80. RESULTS: Inter-RA for the second reading met study requirements (k-alpha = 0.86 [0.81-0.90]) compared to the first reading (0.72 [0.63-0.79]) while combined readings was close to target agreement (0.79 [0.74-0.84]). Removal of 20 readings demonstrating outlier tendencies increased agreement for the first, second, and combined reads (k-alpha = 0.85, 0.89, 0.87, respectively). Intra-RA was sufficient for 4 out of 6 raters (k-alpha > 0.80) and one rater from EU and NA presented subpar intra-RA (k-alpha = 0.64 and 0.74, respectively). Inter-RR met study requirements overall reads (ICC = 0.96 [0.95-0.97]) including the first (0.94 [0.92-0.95]) and second (0.97 [0.97-0.98]) reads, independently. CONCLUSIONS: The Risser+ system showed excellent reliability across multiple reads and raters and demonstrated 79% agreement overall reads and ratings. Agreement increased to over 85% when raters could distinguish Risser 0 + from Risser 5. These slides can be retrieved from electronic supplementary material.

Correction to: The "Risser+" grade: a new grading system to classify skeletal maturity in idiopathic scoliosis.

Unfortunately, the affiliation of the author Negrini S has been incorrectly published in the original version. The complete correct affiliation of this author should read as follows.

Coherent Magnetoelastic Domains in Multiferroic BiFeO_{3} Films.

The physical properties of epitaxial films can fundamentally differ from those of bulk single crystals even above the critical thickness. By a combination of nonresonant x-ray magnetic scattering, neutron diffraction and vector-mapped x-ray magnetic linear dichroism photoemission electron microscopy, we show that epitaxial (111)-BiFeO_{3} films support submicron antiferromagnetic domains, which are magnetoelastically coupled to a coherent crystallographic monoclinic twin structure. This unique texture, which is absent in bulk single crystals, should enable control of magnetism in BiFeO_{3} film devices via epitaxial strain.

Diagnosis of Aortic Graft Infection: A Case Definition by the Management of Aortic Graft Infection Collaboration (MAGIC).

OBJECTIVE/BACKGROUND: The management of aortic graft infection (AGI) is highly complex and in the absence of a universally accepted case definition and evidence-based guidelines, clinical approaches and outcomes vary widely. The objective was to define precise criteria for diagnosing AGI. METHODS: A process of expert review and consensus, involving formal collaboration between vascular surgeons, infection specialists, and radiologists from several English National Health Service hospital Trusts with large vascular services (Management of Aortic Graft Infection Collaboration [MAGIC]), produced the definition. RESULTS: Diagnostic criteria from three categories were classified as major or minor. It is proposed that AGI should be suspected if a single major criterion or two or more minor criteria from different categories are present. AGI is diagnosed if there is one major plus any criterion (major or minor) from another category. (i) Clinical/surgical major criteria comprise intraoperative identification of pus around a graft and situations where direct communication between the prosthesis and a nonsterile site exists, including fistulae, exposed grafts in open wounds, and deployment of an endovascular stent-graft into an infected field (e.g., mycotic aneurysm); minor criteria are localized AGI features or fever ≥38°C, where AGI is the most likely cause. (ii) Radiological major criteria comprise increasing perigraft gas volume on serial computed tomography (CT) imaging or perigraft gas or fluid (≥7 weeks and ≥3 months, respectively) postimplantation; minor criteria include other CT features or evidence from alternative imaging techniques. (iii) Laboratory major criteria comprise isolation of microorganisms from percutaneous aspirates of perigraft fluid, explanted grafts, and other intraoperative specimens; minor criteria are positive blood cultures or elevated inflammatory indices with no alternative source. CONCLUSION: This AGI definition potentially offers a practical and consistent diagnostic standard, essential for comparing clinical management strategies, trial design, and developing evidence-based guidelines. It requires validation that is planned in a multicenter, clinical service database supported by the Vascular Society of Great Britain & Ireland.

Characterization of a bovine isolate Lactobacillus mucosae DPC 6426 which produces an exopolysaccharide composed predominantly of mannose residues.

AIMS: To characterize Lactobacillus strains with EPS-producing ability compared with non-EPS-producing lactobacilli of the same species for technological performance including simulated gastrointestinal tract (GIT) conditions. METHODS AND RESULTS: Characterization of EPS-producing Lactobacillus mucosae DPC 6426 in detail based on 16S rRNA sequencing, and EPS production using scanning electron and atomic force microscopy. The EPS was found to consist of mannosyl residues, with mannose, glucose and galactose found to be the major sugar residues present in an approximate ratio of 3: 2: 2. The strain was compared to non-EPS-producing Lact. mucosae DPC 6420 following exposure to salt, bile, acid and heat stresses. Lact. mucosae DPC 6426 exhibited twofold increased (P < 0·05) survival during 120-min exposure to 5 mol NaCl, threefold increased survival during 90-min exposure to 0·7% (w/v) bile (P < 0·05), threefold increased survival when exposed to simulated gastric juice (P < 0·001) for 10 min and fivefold increased survival during 60-min exposure to HCl (P < 0·01) compared with Lact. mucosae DPC 6420. Furthermore, Lact. mucosae DPC 6426 was found to be more heat tolerant (P < 0·001) compared with Lact. mucosae DPC 6420 during 30-min exposure to 55°C. CONCLUSIONS: These data indicate that the EPS-producing Lact. mucosae DPC 6426 exhibits technological and biological robustness compared with a non-EPS-producing Lact. mucosae strain. SIGNIFICANCE AND IMPACT OF THE STUDY: The data implicate the potential suitability of EPS-producing Lact. mucosae DPC 6426 in food applications and/or as a probiotic culture.

Laparoscopic hysteropexy: a novel technique for uterine preservation surgery.

INTRODUCTION: In recent years uterine preservation surgery for pelvic organ prolapse has become more popular. Traditional operations such as vaginal hysterectomy do not address the underlying pathophysiology of poor connective tissue support, which may result in a higher incidence of recurrent prolapse. METHODS: This video article demonstrates uterine preservation surgery for women with uterine prolapse using laparoscopic abdominal Prolene mesh. CONCLUSIONS: This procedure, apart from possible preservation of fertility in younger women, provides strong apical support, which should be long lasting. The other advantages of laparoscopic surgery are quicker recovery, less pain and better cosmesis.

Laparoscopic hysteropexy: 1- to 4-year follow-up of women postoperatively.

INTRODUCTION AND HYPOTHESIS: Uterine conserving re-suspension surgery has become more popular in recent years. Such surgery may allow preservation of fertility in younger women, but may also have the added benefit of augmenting weak connective tissue and possibly providing stronger apical support than the conventional hysterectomy. Our goal was to evaluate the 1- to 4-year outcome of laparoscopic hysteropexy for the surgical management of uterine prolapse. METHODS: This study was a prospective observational study of 182 consecutive women who underwent laparoscopic hysteropexy, with or without additional vaginal repair, from the beginning of 2007 until the end of 2010. Women were invited to attend a dedicated clinic for interview and their prolapse was assessed using the Patient Global Impression of Improvement (PGI-I), the International Consultation on Incontinence Questionnaire for Vaginal Symptoms (ICIQ-VS) and the pelvic organ prolapse quantification (POP-Q) scale. Wilcoxon signed-rank test was used to compare pre-operative with postoperative data. Complications and women's satisfaction were also noted. RESULTS: One hundred and forty women agreed to participate; the mean interval from operation was 2.1 years (range 1-4.4). Eighty-nine percent of women felt that their prolapse is "very much" or "much" better using PGI-I subjective outcome measure. There was significant improvement for all parameters of ICIQ-VS and POP-Q scoring post-surgery (p < 0.001). Six women (4 %) had further apical prolapse; of these, 3 underwent further prolapse surgery. None of the participants had any mesh exposure. Ninety two percent of participants would recommend the operation. CONCLUSIONS: Laparoscopic hysteropexy is a safe and effective treatment. The 1- to 4-year outcome suggests high patient satisfaction and low rates of apical prolapse recurrence. Longer term follow-up and randomized controlled studies are required.

High-consequence infectious diseases: the conception and development of a multi-disciplinary, interprofessional simulation training programme.

BACKGROUND: High-consequence infectious diseases (HCIDs) represent a group of acute infectious diseases with the potential to impact healthcare systems and public health profoundly. Effective management requires a system-based strategy focused on early detection, initiation of infection prevention and control measures, and appropriate use of personal protective equipment (PPE). Inadequate training in the safe use of HCID PPE, and lack of familiarity with key processes such as HCID waste and spills management, exacerbates the risk posed to healthcare workers (HCWs). Enhanced training opportunities are required to ensure that staff are equipped with the necessary knowledge and capabilities to protect themselves from pathogen exposure and infection. AIM: To create a bespoke interprofessional HCID simulation training programme. METHODS: A detailed learning needs analysis was undertaken, which identified multiple areas amenable to educational intervention. A full-day HCID simulation programme was developed, providing HCWs the opportunity to practice and gain proficiency in various domains. FINDINGS: Six interprofessional participants took part in the HCID simulation programme pilot. All six (100%) participants felt that the stated learning objectives had been achieved, and five and one participants found the programme to be extremely useful (83%) or very useful (17%), respectively. Following refinement based on pilot feedback, a further six courses have been run for 38 participants, of whom 97% found the programme to be extremely useful or very useful. CONCLUSION: The development of a training intervention in the low-frequency, high-risk field of HCIDs had a positive impact. Given the disproportionate impact on HCWs at times of HCID outbreaks, more investment is needed to keep the workforce upskilled.

A 14-year experience with aortic endograft infection: management and results.

OBJECTIVES: The management of thoracic and abdominal aortic endograft infection is complex and associated with high mortality. Cases are rare: a recent systematic review identified 117 reported cases; the largest reported series comprises 12 infected endografts. METHODS: We report 22 consecutive patients with infected abdominal or thoracic aortic endovascular devices implanted from 1998 to 2012. Management included extension with new devices, aneurysm sac drainage of pus/irrigation with antibiotics, endograft explantation, and axillo-(bi)femoral reconstruction. RESULTS: Twenty-two patients (16 men) were identified. Median age was 71 years (range, 43-88 years). Index devices were infra-renal endovascular repair (n = 13), and thoracic endovascular repair (n = 9) all for aneurysmal or pseudoaneurysmal disease. Seven (32%) had prior aortic surgery. Follow-up was complete in all cases; in survivors follow-up was a median of 29 (range, 12-45) months. The mortality from explantation of ten infra-renal devices was 1/10 (10%) on-table and a further 2/10 (20%) within 30 days. Device retention led to disease progression and death in all patients with infected endografts. Sac drainage/irrigation provided only temporary control of sepsis. Device extension can treat rupture, but additional devices became infected. CONCLUSION: Abdominal endograft explantation is high risk but may be curative. Appropriate selection of patients for infected endograft explantation remains a major challenge.

Systems cancer medicine: towards realization of predictive, preventive, personalized and participatory (P4) medicine.

A grand challenge impeding optimal treatment outcomes for patients with cancer arises from the complex nature of the disease: the cellular heterogeneity, the myriad of dysfunctional molecular and genetic networks as results of genetic (somatic) and environmental perturbations. Systems biology, with its holistic approach to understanding fundamental principles in biology, and the empowering technologies in genomics, proteomics, single-cell analysis, microfluidics and computational strategies, enables a comprehensive approach to medicine, which strives to unveil the pathogenic mechanisms of diseases, identify disease biomarkers and begin thinking about new strategies for drug target discovery. The integration of multidimensional high-throughput 'omics' measurements from tumour tissues and corresponding blood specimens, together with new systems strategies for diagnostics, enables the identification of cancer biomarkers that will enable presymptomatic diagnosis, stratification of disease, assessment of disease progression, evaluation of patient response to therapy and the identification of reoccurrences. Whilst some aspects of systems medicine are being adopted in clinical oncology practice through companion molecular diagnostics for personalized therapy, the mounting influx of global quantitative data from both wellness and diseases is shaping up a transformational paradigm in medicine we termed 'predictive', 'preventive', 'personalized', and 'participatory' (P4) medicine, which requires new strategies, both scientific and organizational, to enable bringing this revolution in medicine to patients and to the healthcare system. P4 medicine will have a profound impact on society - transforming the healthcare system, turning around the ever escalating costs of healthcare, digitizing the practice of medicine and creating enormous economic opportunities for those organizations and nations that embrace this revolution.

Human Mendelian pain disorders: a key to discovery and validation of novel analgesics.

We have utilized a novel application of human genetics, illuminating the important role that rare genetic disorders can play in the development of novel drugs that may be of relevance for the treatment of both rare and common diseases. By studying a very rare Mendelian disorder of absent pain perception, congenital indifference to pain, we have defined Nav1.7 (endocded by SCN9A) as a critical and novel target for analgesic development. Strong human validation has emerged with SCN9A gain-of-function mutations causing inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder, both Mendelian disorder of spontaneous or easily evoked pain. Furthermore, variations in the Nav1.7 channel also modulate pain perception in healthy subjects as well as in painful conditions such as osteoarthritis and Parkinson disease. On the basis of this, we have developed a novel compound (XEN402) that exhibits potent, voltage-dependent block of Nav1.7. In a small pilot study, we showed that XEN402 blocks Nav1.7 mediated pain associated with IEM thereby demonstrating the use of rare genetic disorders with mutant target channels as a novel approach to rapid proof-of-concept. Our approach underscores the critical role that human genetics can play by illuminating novel and critical pathways pertinent for drug discovery.

Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012.

Coronaviruses have the potential to cause severe transmissible human disease, as demonstrated by the severe acute respiratory syndrome (SARS) outbreak of 2003. We describe here the clinical and virological features of a novel coronavirus infection causing severe respiratory illness in a patient transferred to London, United Kingdom, from the Gulf region of the Middle East.

The United Kingdom public health response to an imported laboratory confirmed case of a novel coronavirus in September 2012.

On 22 September 2012, a novel coronavirus, very closely related to that from a fatal case in Saudi Arabia three months previously, was detected in a previously well adult transferred to intensive care in London from Qatar with severe respiratory illness. Strict respiratory isolation was instituted. Ten days after last exposure, none of 64 close contacts had developed severe disease, with 13 of 64 reporting mild respiratory symptoms. The novel coronavirus was not detected in 10 of 10 symptomatic contacts tested.

Effects of oligosaccharides in a soybean meal-based diet on fermentative and immune responses in broiler chicks challenged with Eimeria acervulina.

Fermentable oligosaccharides, particularly those found in soybean meal (SBM), may modulate fermentation in the ceca, thus affecting intestinal immune responses to intestinal pathogens. We hypothesized that fermentable oligosaccharides found in SBM would positively affect cecal fermentation and intestinal immune status in chicks challenged with an acute coccidiosis (Eimeria acervulina) infection and fed either a SBM-based diet or a semi-purified soy protein isolate- (SPI) based diet. Using a completely randomized design, 1-d-old broiler chicks (n = 200; 5 replications/treatment; 5 chicks/replication) were assigned to 1 of 4 SBM- or SPI-based diets containing either dietary cellulose (4%) or a fermentable carbohydrate, galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex (4%). On d 9 posthatch, an equal number of chicks on each diet were inoculated with either distilled water (sham control) or E. acervulina (1 × 10(6) oocysts) and then euthanized on d 7 postinoculation. Overall, body weight gain and feed intake were greater (P < 0.01) for SBM-fed chicks, regardless of infection status. Gain:feed ratio was greater (P ≤ 0.05) for SPI-fed chicks except during d 3-7 postinoculation. Infection status, but not fiber source, affected propionate, isobutyrate, isovalerate, and total branched-chain fatty acid concentrations (P ≤ 0.02). Soybean meal-based diets resulted in greater (P ≤ 0.04) short-chain fatty acid and branched-chain fatty acid concentrations than SPI-based diets. Messenger RNA fold changes relative to uninfected SBM-cellulose-fed chicks of all duodenal cytokines were greater (P ≤ 0.01) for infected chicks, and SBM-fed chicks had greater (P < 0.01) interferon-γ and interleukin-12ß expression compared with SPI-fed chicks. Cecal tonsil cytokine expression was also affected (P ≤ 0.02) by infection; however, protein source only affected (P < 0.01) interleukin-1ß expression in this tissue. Overall, a SBM-based diet, compared with a semi-purified SPI-based diet with a different ingredient composition, resulted in greater weight gain, feed intake, and short-chain fatty acid production regardless of infection status, and also greater duodenal cytokine expression in E. acervulina- infected chicks, which is hypothesized to be related to the nutrients and oligosaccharides found in SBM.

The effects of a galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex in broiler chicks challenged with Eimeria acervulina.

Fermentable carbohydrates may enhance the ability of the gastrointestinal tract to defend against pathogenic infection. We hypothesized that a mannose-rich, galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex would positively impact immune status and prevent weight loss resulting from acute coccidiosis (Eimeria acervulina) infection of chicks. Using a completely randomized design, 1-d-old commercial broiler chicks (n = 160; 4 replications/treatment; 5 chicks/replication) were assigned to one of 4 corn-soybean meal-based diets containing supplemental GGMO-AX (0, 1, 2, or 4%) that replaced dietary cellulose. On d 9 posthatch, an equal number of chicks on each diet were inoculated with either distilled water (sham control) or E. acervulina (1 × 10(6) oocysts). All birds were euthanized on d 7 postinoculation (PI) for collection of cecal contents and duodenal tissue. Overall, BW gain of chicks was not affected by diet PI, whereas infection decreased (P < 0.01) weight gain on d 0 to 7 PI. Feed intake was not affected by dietary treatment, but infection decreased (P < 0.01) feed intake on d 0 to 7 PI. Overall, infection, but not diet, decreased (P < 0.01) G:F on d 0 to 7 PI. Cecal propionate concentrations were independently affected by infection and diet, while butyrate concentrations were affected only by infection (P = 0.02). Cecal Bifidobacterium spp. populations were affected (P < 0.01) by diet, with the 2% GGMO-AX resulting in the highest cfu/g of cecal contents (on a DM basis). Messenger RNA expression of all duodenal cytokines evaluated was affected by infection status (P ≤ 0.02) but not by dietary treatment alone. Supplementing 4% GGMO-AX consistently resulted in the greatest fold change in proinflammatory cytokine expression, while inhibiting antiinflammatory cytokine expression, which indicates a more robust innate immune response. Despite decreasing performance, 4% dietary GGMO-AX improved select fermentation indices and the innate intestinal immune response to an acute E. acervulina infection.

Ingestion of a novel galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex affected growth performance and fermentative and immunological characteristics of broiler chicks challenged with Salmonella typhimurium.

Fermentable carbohydrates may enhance the ability of the gastrointestinal tract to defend against a pathogenic infection. We hypothesized that a galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex would positively affect immune status and prevent colonization and shedding in Salmonella typhimurium-infected chicks. Using a completely randomized design, 1-d-old commercial broiler chicks (n = 240 chicks; 4 replications/treatment; 5 chicks/replication) were assigned to 1 of 6 dietary treatments differing in concentration of GGMO-AX (0, 1, 2, or 4%) or containing 2% Safmannan or 2% short-chain fructooligosaccharides. Cellulose was used to make diets iso-total dietary fiber. On d 10 posthatch, an equal number of chicks on each diet were inoculated with either phosphate-buffered saline (sham control) or Salmonella typhimurium (1 × 10(8) cfu). All birds were euthanized on d 10 postinoculation (PI) for collection of intestinal contents and select tissues. Body weight gain and feed intake of chicks were greater (P < 0.05) in infected chicks PI for all time periods, except for weight gain on d 0 to 3 PI. Gain:feed was affected (P < 0.05) by diet, with Safmannan-fed chicks having the highest G:F and 1% GGMO-AX-fed chicks having the lowest. The GGMO-AX substrate demonstrated effects similar to a prebiotic substrate as indicated by increased cecal short-chain fatty acid concentrations, decreased cecal pH, and increased populations of Lactobacillus spp. and Bifidobacteria spp. as dietary GGMO-AX concentration increased. Excreta Salmonella typhimurium populations on d 5 and 10 PI, and ileal and cecal Salmonella typhimurium populations, tended to be affected (P < 0.10) by the main effect of diet. Messenger RNA expression of IFN-γ in the cecal tonsils was the only cytokine independently affected by infection and diet (P < 0.01). Chicks fed 2 and 4% GGMO-AX had similar expressions of IFN-γ and IL-1ß, regardless of infection, suggesting that Salmonella typhimurium virulence was suppressed. Dietary supplementation with GGMO-AX resulted in prebiotic-like effects but did not limit Salmonella typhimurium intestinal colonization or shedding, but possibly decreased the virulence of Salmonella typhimurium within the digestive tract.