Divergent Relationships between Fecal Microbiota and Metabolome following Distinct Antibiotic-Induced Disruptions

This is an openaccess article distributed under the terms of the Creative Commons attribution 4.0 International license.The intestinal microbiome plays an essential role in regulating many aspects of host physiology, and its disruption through antibiotic exposure has been implicated in the development of a range of serious pathologies. The complex metabolic relationships that exist between members of the intestinal microbiota and the potential redundancy in functional pathways mean that an integrative analysis of changes in both structure and function are needed to understand the impact of antibiotic exposure. We used a combination of next-generation sequencing and nuclear magnetic resonance (NMR) metabolomics to characterize the effects of two clinically important antibiotic treatments, ciprofloxacin and vancomycin-imipenem, on the intestinal microbiomes of female C57BL/6 mice. This assessment was performed longitudinally and encompassed both antibiotic challenge and subsequent microbiome reestablishment. Both antibiotic treatments significantly altered the microbiota and metabolite compositions of fecal pellets during challenge and recovery. Spearman’s correlation analysis of microbiota and NMR data revealed that, while some metabolites could be correlated with individual operational taxonomic units (OTUs), frequently multiple OTUs were associated with a significant change in a given metabolite. Furthermore, one metabolite, arginine, can be associated with increases/decreases in different sets of OTUs under differing conditions. Taken together, these findings indicate that reliance on shifts in one data set alone will generate an incomplete picture of the functional effect of antibiotic intervention. A full mechanistic understanding will require knowledge of the baseline microbiota composition, combined with both a comparison and an integration of microbiota, metabolomics, and phenotypic data

Postoperative differences between colonization and infection after pediatric cardiac surgery-a propensity matched analysis

BACKGROUND: The objective of this study was to identify the postoperative risk factors associated with the conversion of colonization to postoperative infection in pediatric patients undergoing cardiac surgery. METHODS: Following approval from the Institutional Review Board, patient demographics, co-morbidities, surgery details, transfusion requirements, inotropic infusions, laboratory parameters and positive microbial results were recorded during the hospital stay, and the patients were divided into two groups: patients with clinical signs of infection and patients with only positive cultures but without infection during the postoperative period. Using propensity scores, 141 patients with infection were matched to 141 patients with positive microbial cultures but without signs of infection. Our database consisted of 1665 consecutive pediatric patients who underwent cardiac surgery between January 2004 and December 2008 at a single center. The association between the patient group with infection and the group with colonization was analyzed after propensity score matching of the perioperative variables. RESULTS: 179 patients (9.3%) had infection, and 253 patients (15.2%) had colonization. The occurrence of Gram-positive species was significantly greater in the colonization group (p=0.004). The C-reactive protein levels on the first and second postoperative days were significantly greater in the infection group (p=0.02 and p=0.05, respectively). The sum of all the positive cultures obtained during the postoperative period was greater in the infection group compared to the colonization group (p=0.02). The length of the intensive care unit stay (p<0.001) was significantly longer in the infection group compared to the control group. CONCLUSIONS: Based on our results, we uncovered independent relationships between the conversion of colonization to infection regarding positive S. aureus and bloodstream results, as well as significant differences between the two groups regarding postoperative C-reactive protein levels and white blood cell counts

Improving the outcome of infants born at <30 weeks' gestation - a randomized controlled trial of preventative care at home

Background: Early developmental interventions to prevent the high rate of neurodevelopmental problems in very preterm children, including cognitive, motor and behavioral impairments, are urgently needed. These interventions should be multi-faceted and include modules for caregivers given their high rates of mental health problems

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Land and Resource planning under Native Title : towards an initial model. by Marcus B. Lane, A. Lex Brown and Athol Chase

This article proposes a model for the development of land management and land use plans under native title

Fine structure in the luminosity function in young stellar populations with

Context. A pioneering study showed that the fine structure in the luminosity function (LF) of young star clusters contains information about the evolutionary stage (age) and composition of the stellar population. The notable features include the H-peak, which is the result of the onset of hydrogen burning turning pre-main sequence stars into main sequence stars. The feature moves toward the faint end of the LF, and eventually disappears as the population evolves. Another detectable feature is the Wielen dip, a dip at MV ≃ 7 mag in the LF first identified in 1974 for stars in the solar environment. Later studies also identified this feature in the LF of star clusters. The Wielen dip is caused by the increased importance of H− opacity in a certain range of low-mass stars. Aims. We studied the detailed structure in the luminosity function using the data from Gaia DR2 and PARSEC stellar evolution models with the aim to further our understanding of young stellar populations. Methods. We analyzed the astrometric properties of stars in the solar neighborhood (< 20 pc) and in various relatively nearby (< 400 pc) young (< 50 Myr) open clusters and OB associations, and compare the features in the luminosity function with those generated by PARSEC models. Results. The Wielen dip is confirmed in the LF of all the populations, including the solar neighborhood, at MG ≃ 7 mag. The H-peak is present in the LF of the field stars in the solar neighborhood. It likely signals that the population is mixed with a significant number of stars younger than 100 Myr. The H-peak is found in the LF of young open clusters and OB associations, and its location varies with age. The PARSEC evolutionary models predict that the H-peak moves from ∼ − 1 mag towards ∼ + 6 mag in MG for populations with ages increasing from 1 to ∼70 Myr. Our observations with Gaia DR2 confirm the evolution of the H-peak from ∼5 Myr up to ∼47 Myr. We provide a calibration function between MG and age that works in the age domain between 1 and 30 Myr. Conclusions. The fine structure in the luminosity function in young stellar populations can be used to estimate their age

Parental mental health before and during pregnancy and offspring birth outcomes:a 20-year preconception cohort of maternal and paternal exposure

Background: Preterm birth (PTB) and small for gestational age (SGA) are increasingly prevalent, with major consequences for health and development into later life. There is emerging evidence that some risk processes begin before pregnancy. We report on associations between maternal and paternal common mental disorders (CMD) before and during pregnancy and offspring PTB and SGA. Methods: 398 women with 609 infants and 267 men with 421 infants were assessed repeatedly for CMD symptoms before pregnancy between age 14 and 29 and during pregnancy. Associations between preconception and antenatal CMD symptoms and offspring gestational age/PTB and size for gestational age/SGA were estimated using linear and Poisson regression. Findings: In men, persistent preconception CMD across adolescence and young adulthood predicted offspring PTB after adjustment for ethnicity, education, BMI and adolescent substance use (adjusted RR 7·0, 95% CI 1·8,26·8), corresponding to a population attributable fraction of 31% of preterm births. In women, antenatal CMD symptoms predicted offspring PTB (adjusted RR 4·4, 95% CI 1·4,14·1). There was little evidence of associations with SGA. Interpretation: This first report of an association between paternal preconception mental health and offspring gestational age, while requiring replication in larger samples, complements earlier work on stress in animals, and further strengthens the case for expanding preconception mental health care to both men and women. Funding: National Health and Medical Research Council (Australia), Victorian Health Promotion Foundation, Australian Rotary Health, Colonial Foundation, Perpetual Trustees, Financial Markets Foundation for Children (Australia), Royal Children's Hospital Foundation, Murdoch Children's Research Institute, Australian Research Council