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AbstractBackgroundMicrobial constituents of the gut microbiome interact with each other and the host to alter the luminal environment and impact development, motility, and homeostasis of the gut. Powerful methods are becoming available to investigate connections between the gut microbiome and human health. While high‐throughput sequencing of 16S rRNA genes can be used to identify and enumerate microbes in the gut, advances in several techniques (e.g., metagenomics, metatranscriptomics, metabolomics, and metaproteomics) are providing a clearer view as to the specific activities of the microbiota in the context of functional host–microbe interactions. Testing emergent hypotheses regarding microbial effects on host biology, which arise from analyses of ‘Big Data’ generated from massive parallel high‐throughput sequencing technology and spectroscopic techniques, to guide translational research is an important goal for the future. Insights regarding the fundamental operating principles of the gut microbiota should lay the foundation for rational manipulation of the microbiota to promote human health.PurposeIn this review, we provide an overview of current research on the gut microbiome emphasizing current state‐of‐the‐art technologies, approaches, and directions for improvement of our understanding of the impact of the gut microbiota with specific focus on gastrointestinal motility disorders.

BACKGROUND High-sensitivity cardiac troponin (hs-cTn) assays are now available that can detect measurable troponin in significantly more individuals in the general population than conventional assays. The clinical use of these hs-cTn assays depends on the development of proper reference values. Therefore, our objective was to define hs-cTnI reference values and determinants in the general community, in a healthy reference cohort, and in subsets with diseases. MATERIALS AND METHODS A well-characterized community-based cohort of 2042 study participants underwent clinical assessment and echocardiographic evaluation. Baseline hs-cTnI measurements were obtained in 1843 individuals. A healthy reference cohort (n = 565) without cardiac, renal, or echocardiographic abnormalities was identified. RESULTS Measurable hs-cTnI was identified in 1716 (93%) of the community-based study cohort and 499 (88%) of the healthy reference cohort. Parameters that significantly contributed to higher hs-cTnI concentrations in the healthy reference cohort included age, male sex, systolic blood pressure, and left ventricular mass. Glomerular filtration rate and body mass index were not independently associated with hs-cTnI in the healthy reference cohort. Individuals with diastolic and systolic dysfunction, hypertension, and coronary artery disease (but not impaired renal function) had significantly higher hs-cTnI values than the healthy reference cohort. CONCLUSIONS We assessed an hs-cTnI assay with the aid of echocardiographic imaging in a large, well-characterized community-based cohort. hs-cTnI is remarkably sensitive in the general population, and there are important sex and age differences among healthy reference individuals. These results have important implications for defining hs-cTnI reference values and identifying disease.

Background— We examined the risk of stroke or systemic embolism (SSE) conferred by heart failure (HF) and left ventricular systolic dysfunction (LVSD) in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation Trial (ARISTOTLE), as well as the effect of apixaban versus warfarin. Methods and Results— The risk of a number of outcomes, including the composite of SSE or death (to take account of competing risks) and composite of SSE, major bleeding, or death (net clinical benefit) were calculated in 3 patient groups: (1) no HF/no LVSD (n=8728), (2) HF/no LVSD (n=3207), and (3) LVSD with/without symptomatic HF (n=2736). The rate of both outcomes was highest in patients with LVSD (SSE or death 8.06; SSE, major bleeding, or death 10.46 per 100 patient-years), intermediate for HF but preserved LV systolic function (5.32; 7.24), and lowest in patients without HF or LVSD (1.54; 5.27); each comparison P <0.0001. Each outcome was less frequent in patients treated with apixaban: in all ARISTOTLE patients, the apixaban/warfarin hazard ratio for SSE or death was 0.89 (95% confidence interval, 0.81–0.98; P =0.02); for SSE, major bleed, or death it was 0.85 (0.78–0.92; P <0.001). There was no heterogeneity of treatment effect across the 3 groups. Conclusions— Patients with LVSD (with/without HF) had a higher risk of SSE or death (but similar rate of SSE) compared with patients with HF but preserved LV systolic function; both had a greater risk than patients without either HF or LVSD. Apixaban reduced the risk of both outcomes more than warfarin in all 3 patient groups. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00412984.

Objectives To investigate the incidence of carcinoma in situ ( CIS ) in Australia and examine implications for its diagnosis and management, as CIS of the urinary bladder is a non‐reportable disease in Australia. Methods Analysis of annual hospitalisation data using A ustralian I nstitute of H ealth and W elfare ( AIHW ) datasets showed an increase in CIS from 2001 onwards. To determine whether the increase seen with AIHW data represented a true increase in the rates offices, patient level data was examined using the Centre for Health record linkage ( CHeReL ) datasets. Results CHeReL linked data of 13 790 males and 5902 females, calculated the average incidence of CIS to be 20.9 per 100 000 and 6.5 per 100 000 respectively in those aged > 50 years, showing a rapid increase in the rates of CIS from 2001. There was an 11% ( P = 0.04) and 14% ( P = 0.02) annual increase in incidence of CIS in men and women and these rates increased with age. Conclusions National data ( AIHW ) substantially underestimate the incidence of CIS in the Australian population. Patient level data suggest CIS rates are rapidly increasing in Australia despite high treatment rates. Closer surveillance and awareness of these high rates warrants further study and we recommend that CIS be considered a reportable disease.

Abstract Psychological stress can lead to asthma exacerbations in some patients. It is our hypothesis that the stress effect can occur through an enhancement of allergic inflammatory response. To investigate this possibility, airway antigen challenge was evaluated in 20 college students with mild asthma during both a low-stress phase (midsemester or two weeks postfinal examination) and a stress phase (final examination week). Subjects completed questionnaires to assess psychological state and underwent inhaled antigen challenge. Sputum samples were collected before challenge, and six and 24 hours and seven days postchallenge. Leukocytes were counted and eosinophil-derived neurotoxin (EDN) was measured in sputum supernates. Sputum cells were cultured and stimulated ex vivo with phytohemagglutinin (10 μ g/ml), and culture supernates were assayed for interleukin-5 (IL-5) and interferon- γ by enzyme-linked immunosorbent assay. Sputum eosinophils and EDN levels significantly increased at six and 24 hours postchallenge and were enhanced during the stress phase (p &lt; 0.01). IL-5 generation by sputum cells was also increased at 24 hours during stress and correlated with airway eosinophils (rs = 0.65, p &lt; 0.05). Students' anxiety and depression scores were significantly higher during the examination period. Our findings suggest that stress associated with final examinations can act as a cofactor to increase eosinophilic airway inflammation to antigen challenge and thus may enhance asthma severity.

Abstract A donor lung is injured during preservation and is generally thought to be further injured by reperfusion on transplantation. Donor lungs from 15 adult male Lewis rats preserved by flush perfusion with cold Marshall's solution at 4° C were examined by scanning and by quantitative transmission electron microscopy after 2, 4, or 7 h of storage at 4° C and after transplantation (syngeneic) at 4 or 12 h (six animals per time interval). During preservation of the donor lung, capillary morphology changed rapidly. Both endothelial cells and type I pneumonocytes thinned (surface/volume ratio increased by 2 h in both; P &lt; 0.001). Pericapillary edema developed involving the blood-gas barrier. Basement membrane thickness increased significantly (P &lt; 0.001). Occasional breakage of the endothelial cell sheet occurred after 4 h of preservation, but even after 7 h of preservation there was no evidence of irreversible cell damage. The lamellar bodies of type II pneumocytes aggregated. Changes increased in severity with increase in preservation time. After transplantation, type I and type II pneumonocytes recovered after 12 h, but it took longer for the endothelial cell morphology to recover. Edema decreased rapidly during the first 4 h, despite the number of adherent neutrophils increasing 3-fold. The pulmonary capillaries of the transplanted lung showed no structural evidence of additional reperfusion injury, indicating a satisfactory method of preservation.