Preterm gut microbiota and metabolome following discharge from intensive care

The development of the preterm gut microbiome is important for immediate and longer-term health following birth. We aimed to determine if modifications to the preterm gut on the neonatal intensive care unit (NICU) impacted the gut microbiota and metabolome long-term. Stool samples were collected from 29 infants ages 1–3 years post discharge (PD) from a single NICU. Additional NICU samples were included from 14/29 infants. Being diagnosed with disease or receiving increased antibiotics while on the NICU did not significantly impact the microbiome PD. Significant decreases in common NICU organisms including K. oxytoca and E. faecalis and increases in common adult organisms including Akkermansia sp., Blautia sp., and Bacteroides sp. and significantly different Shannon diversity was shown between NICU and PD samples. The metabolome increased in complexity, but while PD samples had unique bacterial profiles we observed comparable metabolomic profiles. The preterm gut microbiome is able to develop complexity comparable to healthy term infants despite limited environmental exposures, high levels of antibiotic administration, and of the presence of serious disease. Further work is needed to establish the direct effect of weaning as a key event in promoting future gut health

Deployment of regulatory genes during gastrulation and germ layer specification in a model spiralian mollusc Crepidula

© 2015 Wiley Periodicals, Inc. Background: During gastrulation, endoderm and mesoderm are specified from a bipotential precursor (endomesoderm) that is argued to be homologous across bilaterians. Spiralians also generate mesoderm from ectodermal precursors (ectomesoderm), which arises near the blastopore. While a conserved gene regulatory network controls specification of endomesoderm in deuterostomes and ecdysozoans, little is known about genes controlling specification or behavior of either source of spiralian mesoderm or the digestive tract. Results: Using the mollusc Crepidula, we examined conserved regulatory factors and compared their expression to fate maps to score expression in the germ layers, blastopore lip, and digestive tract. Many genes were expressed in both ecto- and endomesoderm, but only five were expressed in ectomesoderm exclusively. The latter may contribute to epithelial-to-mesenchymal transition seen in ectomesoderm. Conclusions: We present the first comparison of genes expressed during spiralian gastrulation in the context of high-resolution fate maps. We found variation of genes expressed in the blastopore lip, mouth, and cells that will form the anus. Shared expression of many genes in both mesodermal sources suggests that components of the conserved endomesoderm program were either co-opted for ectomesoderm formation or that ecto- and endomesoderm are derived from a common mesodermal precursor that became subdivided into distinct domains during evolution.Spanish MICINN and the UAM, and funded by project CGL2011-29916 (MICINN)Peer Reviewe

Spontaneous Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis Describing the Diagnostic Accuracy of History, Physical Examination, Imaging, and Lumbar Puncture With an Exploration of Test Thresholds.

BACKGROUND: Spontaneous subarachnoid hemorrhage (SAH) is a rare, but serious etiology of headache. The diagnosis of SAH is especially challenging in alert, neurologically intact patients, as missed or delayed diagnosis can be catastrophic. OBJECTIVES: The objective was to perform a diagnostic accuracy systematic review and meta-analysis of history, physical examination, cerebrospinal fluid (CSF) tests, computed tomography (CT), and clinical decision rules for spontaneous SAH. A secondary objective was to delineate probability of disease thresholds for imaging and lumbar puncture (LP). METHODS: PubMed, Embase, Scopus, and research meeting abstracts were searched up to June 2015 for studies of emergency department patients with acute headache clinically concerning for spontaneous SAH. QUADAS-2 was used to assess study quality and, when appropriate, meta-analysis was conducted using random effects models. Outcomes were sensitivity, specificity, and positive (LR+) and negative (LR-) likelihood ratios. To identify test and treatment thresholds, we employed the Pauker-Kassirer method with Bernstein test indication curves using the summary estimates of diagnostic accuracy. RESULTS: A total of 5,022 publications were identified, of which 122 underwent full-text review; 22 studies were included (average SAH prevalence = 7.5%). Diagnostic studies differed in assessment of history and physical examination findings, CT technology, analytical techniques used to identify xanthochromia, and criterion standards for SAH. Study quality by QUADAS-2 was variable; however, most had a relatively low risk of biases. A history of neck pain (LR+ = 4.1; 95% confidence interval [CI] = 2.2 to 7.6) and neck stiffness on physical examination (LR+ = 6.6; 95% CI = 4.0 to 11.0) were the individual findings most strongly associated with SAH. Combinations of findings may rule out SAH, yet promising clinical decision rules await external validation. Noncontrast cranial CT within 6 hours of headache onset accurately ruled in (LR+ = 230; 95% CI = 6 to 8,700) and ruled out SAH (LR- = 0.01; 95% CI = 0 to 0.04); CT beyond 6 hours had a LR- of 0.07 (95% CI = 0.01 to 0.61). CSF analyses had lower diagnostic accuracy, whether using red blood cell (RBC) count or xanthochromia. At a threshold RBC count of 1,000 × 10(6) /L, the LR+ was 5.7 (95% CI = 1.4 to 23) and LR- was 0.21 (95% CI = 0.03 to 1.7). Using the pooled estimates of diagnostic accuracy and testing risks and benefits, we estimate that LP only benefits CT-negative patients when the pre-LP probability of SAH is on the order of 5%, which corresponds to a pre-CT probability greater than 20%. CONCLUSIONS: Less than one in 10 headache patients concerning for SAH are ultimately diagnosed with SAH in recent studies. While certain symptoms and signs increase or decrease the likelihood of SAH, no single characteristic is sufficient to rule in or rule out SAH. Within 6 hours of symptom onset, noncontrast cranial CT is highly accurate, while a negative CT beyond 6 hours substantially reduces the likelihood of SAH. LP appears to benefit relatively few patients within a narrow pretest probability range. With improvements in CT technology and an expanding body of evidence, test thresholds for LP may become more precise, obviating the need for a post-CT LP in more acute headache patients. Existing SAH clinical decision rules await external validation, but offer the potential to identify subsets most likely to benefit from post-CT LP, angiography, or no further testing

Impaired decisional impulsivity in pathological videogamers

Abstract Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management

Cumulative impact assessment for ecosystem-based marine spatial planning

Claims for ocean space are growing while marine ecosystems suffer from centuries of insufficient care. Human pressures from runoff, atmospheric emissions, marine pollution, fishing, shipping, military operations and other activities wear on habitats and populations. Ecosystem-based marine spatial planning (MSP) has emerged worldwide as a strategic instrument for handling conflicting spatial claims among competing sectors and the environment. The twofold objective of both boosting the blue economy and protecting the environment is challenging in practice and marine planners need decision support. Cumulative Impact Assessment (CIA) was originally developed to provide an overview of the human imprint on the world\u27s ocean ecosystems. We have now added a scenario component to the CIA model and used it within Swedish ecosystem-based MSP. This has allowed us to project environmental impacts for different planning alternatives throughout the planning process, strengthening the integration of environmental considerations into strategic decision-making. Every MSP decision may entail a local shift of environmental impact, causing positive or negative consequences for ecosystem components. The results from Swedish MSP in the North Sea and Baltic Sea illustrate that MSP certainly has the potential to lower net cumulative environmental impact, both locally and across sea basins, as long as environmental values are rated high and prevailing pressures derive from activities that are part of MSP. By synthesizing innumerous data into comprehensible decision support that informs marine planners of the likely environmental consequences of different options, CIA enables ecosystem-based MSP in practice

Parallaxes and proper motions for 20 open clusters as based on the new Hipparcos catalogue

A new reduction of the astrometric data as produced by the Hipparcos mission has been published, claiming that the accuracies for nearly all stars brighter than magnitude $\mathrm{Hp}=8$ are improved, by up to a factor 4, compared to the original catalogue. As correlations between the underlying abscissa residuals have also been reduced by more than an order of magnitude to an insignificant level, our ability to determine reliable parallaxes and proper motions for open clusters should be improved. The new Hipparcos astrometric catalogue is used to derive mean parallax and proper motion estimates for 20 open clusters. The HR-diagrams of the nearest clusters are compared and combined to provide future input to sets of observational isochrones. The positions of the cluster HR diagrams are consistent within different groups of clusters shown for example by the near-perfect alignment of the sequences for the Hyades and Praesepe, for Coma Ber and UMa, and for the Pleiades, NGC 2516, and Blanco 1. The groups are mutually consistent when systematic differences in $\Delta c_0$ are taken into account, where the effect of these differences on the absolute magnitudes has been calibrated using field-star observations.Comment: 34 pages, 36 figures, 7 tables. Accepted for publication by A&

The Female Lower Genital Tract Is a Privileged Compartment with IL-10 Producing Dendritic Cells and Poor Th1 Immunity following Chlamydia trachomatis Infection

While a primary genital tract infection with C. trachomatis stimulates partial-protection against re-infection, it may also result in severe inflammation and tissue destruction. Here we have dissected whether functional compartments exist in the genital tract that restrict Th1-mediated protective immunity. Apart from the Th1-subset, little is known about the role of other CD4+ T cell subsets in response to a genital tract chlamydial infection. Therefore, we investigated CD4+ T cell subset differentiation in the genital tract using RT-PCR for expression of critical transcription factors and cytokines in the upper (UGT) and lower genital tract (LGT) of female C57BL/6 mice in response to C. trachomatis serovar D infection. We found that the Th1 subset dominated the UGT, as IFN-γ and T-bet mRNA expression were high, while GATA-3 was low following genital infection with C. trachomatis serovar D. By contrast, IL-10 and GATA-3 mRNA dominated the LGT, suggesting the presence of Th2 cells. These functional compartments also attracted regulatory T cells (Tregs) differently as increased FoxP3 mRNA expression was seen primarily in the UGT. Although IL-17A mRNA was somewhat up-regulated in the LGT, no significant change in RORγ-t mRNA expression was observed, suggesting no involvement of Th17 cells. The dichotomy between the LGT and UGT was maintained during infection by IL-10 because in IL-10-deficient mice the distinction between the two compartments was completely lost and a dramatic shift to the predominance of Th1 cells in the LGT occurred. Unexpectedly, the major source of IL-10 was CD11c+ CD11b+ DC, probably creating an anti-inflammatory privileged site in the LGT

Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research

<b>Background</b> Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.<p></p> <b>Methods and findings</b> The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.<p></p> <b>Conclusions</b> Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems

A comparison of weather variables linked to infectious disease patterns using laboratory addresses and patient residence addresses

Background: To understand the impact of weather on infectious diseases, information on weather parameters at patient locations is needed, but this is not always accessible due to confidentiality or data availability. Weather parameters at nearby locations are often used as a proxy, but the accuracy of this practice is not known. Methods: Daily Campylobacter and Cryptosporidium cases across England and Wales were linked to local temperature and rainfall at the residence postcodes of the patients and at the corresponding postcodes of the laboratory where the patient’s specimen was tested. The paired values of daily rainfall and temperature for the laboratory versus residence postcodes were interpolated from weather station data, and the results were analysed for agreement using linear regression. We also assessed potential dependency of the findings on the relative geographic distance between the patient’s residence and the laboratory. Results: There was significant and strong agreement between the daily values of rainfall and temperature at diagnostic laboratories with the values at the patient residence postcodes for samples containing the pathogens Campylobacter or Cryptosporidium. For rainfall, the R-squared was 0.96 for the former and 0.97 for the latter, and for maximum daily temperature, the R-squared was 0.99 for both. The overall mean distance between the patient residence and the laboratory was 11.9 km; however, the distribution of these distances exhibited a heavy tail, with some rare situations where the distance between the patient residence and the laboratory was larger than 500 km. These large distances impact the distributions of the weather variable discrepancies (i.e. the differences between weather parameters estimated at patient residence postcodes and those at laboratory postcodes), with discrepancies up to ±10 °C for the minimum and maximum temperature and 20 mm for rainfall. Nevertheless, the distributions of discrepancies (estimated separately for minimum and maximum temperature and rainfall), based on the cases where the distance between the patient residence and the laboratory was within 20 km, still exhibited tails somewhat longer than the corresponding exponential fits suggesting modest small scale variations in temperature and rainfall. Conclusion: The findings confirm that, for the purposes of studying the relationships between meteorological variables and infectious diseases using data based on laboratory postcodes, the weather results are sufficiently similar to justify the use of laboratory postcode as a surrogate for domestic postcode. Exclusion of the small percentage of cases where there is a large distance between the residence and the laboratory could increase the precision of estimates, but there are generally strong associations between daily weather parameters at residence and laboratory