Upper Airways Microbiota in Antibiotic-Naive Wheezing and Healthy Infants from the Tropics of Rural Ecuador

Background: Observations that the airway microbiome is disturbed in asthma may be confounded by the widespread use of antibiotics and inhaled steroids. We have therefore examined the oropharyngeal microbiome in early onset wheezinginfants from a rural area of tropical Ecuador where antibiotic usage is minimal and glucocorticoid usage is absent. Materials and Methods: We performed pyrosequencing of amplicons of the polymorphic bacterial 16S rRNA gene from oropharyngeal samples from 24 infants with non-infectious early onset wheezing and 24 healthy controls (average age 10.2 months). We analyzed microbial community structure and differences between cases and controls by QIIME software. Results: We obtained 76,627 high quality sequences classified into 182 operational taxonomic units (OTUs). Firmicutes was the most common and diverse phylum (71.22% of sequences) with Streptococcus being the most common genus (49.72%). Known pathogens were found significantly more often in cases of infantile wheeze compared to controls, exemplified by Haemophilus spp. (OR = 2.12, 95% Confidence Interval (CI) 1.82–2.47; P = 5.46610223) and Staphylococcus spp. (OR = 124.1, 95%CI 59.0–261.2; P = 1.876102241). Other OTUs were less common in cases than controls, notably Veillonella spp. (OR = 0.59, 95%CI = 0.56–0.62; P = 8.06610286). Discussion: The airway microbiota appeared to contain many more Streptococci than found in Western Europe and the USA. Comparisons between healthy and wheezing infants revealed a significant difference in several bacterial phylotypes that were not confounded by antibiotics or use of inhaled steroids. The increased prevalence of pathogens such as Haemophilus and Staphylococcus spp. in cases may contribute to wheezing illnesses in this age group

Water Cycle Changes

This chapter assesses multiple lines of evidence to evaluate past, present and future changes in the global water cycle. It complements material in Chapters 2, 3 and 4 on observed and projected changes in the water cycle, and Chapters 10 and 11 on regional climate change and extreme events. The assessment includes the physical basis for water cycle changes, observed changes in the water cycle and attribution of their causes, future projections and related key uncertainties, and the potential for abrupt change. Paleoclimate evidence, observations, reanalyses and global and regional model simulations are considered. The assessment shows widespread, nonuniform human-caused alterations of the water cycle, which have been obscured by a competition between different drivers across the 20th century and that will be increasingly dominated by greenhouse gas forcing at the global scale

Wnt, Hedgehog and Junctional Armadillo/β-Catenin Establish Planar Polarity in the Drosophila Embryo

To generate specialized structures, cells must obtain positional and directional information. In multi-cellular organisms, cells use the non-canonical Wnt or planar cell polarity (PCP) signaling pathway to establish directionality within a cell. In vertebrates, several Wnt molecules have been proposed as permissible polarity signals, but none has been shown to provide a directional cue. While PCP signaling components are conserved from human to fly, no PCP ligands have been reported in Drosophila. Here we report that in the epidermis of the Drosophila embryo two signaling molecules, Hedgehog (Hh) and Wingless (Wg or Wnt1), provide directional cues that induce the proper orientation of Actin-rich structures in the larval cuticle. We further find that proper polarity in the late embryo also involves the asymmetric distribution and phosphorylation of Armadillo (Arm or β-catenin) at the membrane and that interference with this Arm phosphorylation leads to polarity defects. Our results suggest new roles for Hh and Wg as instructive polarizing cues that help establish directionality within a cell sheet, and a new polarity-signaling role for the membrane fraction of the oncoprotein Arm

Off-hours admission and mortality in two pediatric intensive care units without 24-h in-house senior staff attendance

To compare risk-adjusted mortality of children non-electively admitted during off-hours with risk-adjusted mortality of children admitted during office hours to two pediatric intensive care units (PICUs) without 24-h in-house attendance of senior staff. Prospective observational study, performed between January 2003 and December 2007, in two PICUs without 24-h in-house attendance of senior staff, located in tertiary referral children's hospitals in the Netherlands. Standardized mortality rates (SMRs) of patients admitted during off-hours were compared to SMRs of patients admitted during office hours using Pediatric Index of Mortality (PIM1) and Pediatric Risk of Mortality (PRISM2) scores. Office hours were defined as week days between 8:00 a.m. and 6:00 p.m., with in-house attendance of senior staff, and off-hours as week days between 6:00 p.m. and 8:00 a.m., Saturdays, Sundays and public holidays, with one resident covering the PICU and senior staff directly available on-call. Of 3,212 non-elective patients admitted to the PICUs, 2,122 (66%) were admitted during off-hours. SMRs calculated according to PIM1 and PRISM2 did not show a significant difference with those of patients admitted during office hours. There was no significant effect of admission time on mortality in multivariate logistic regression with odds ratios of death in off-hours of 0.95 (PIM1, 95% CI 0.71-1.27, p = 0.73) and 1.03 (PRISM2, 95% CI 0.76-1.39, p = 0.82). Off-hours admission to our PICUs without 24-h in-house attendance of senior staff was not associated with higher SMRs than admission during office hours when senior staff were available in-house

Importance of the Collagen Adhesin Ace in Pathogenesis and Protection against Enterococcus faecalis Experimental Endocarditis

Ace is an adhesin to collagen from Enterococcus faecalis expressed conditionally after growth in serum or in the presence of collagen. Here, we generated an ace deletion mutant and showed that it was significantly attenuated versus wild-type OG1RF in a mixed infection rat endocarditis model (P<0.0001), while no differences were observed in a peritonitis model. Complemented OG1RFΔace (pAT392::ace) enhanced early (4 h) heart valve colonization versus OG1RFΔace (pAT392) (P = 0.0418), suggesting that Ace expression is important for early attachment. By flow cytometry using specific anti-recombinant Ace (rAce) immunoglobulins (Igs), we showed in vivo expression of Ace by OG1RF cells obtained directly from infected vegetations, consistent with our previous finding of anti-Ace antibodies in E. faecalis endocarditis patient sera. Finally, rats actively immunized against rAce were less susceptible to infection by OG1RF than non-immunized (P = 0.0004) or sham-immunized (P = 0.0475) by CFU counts. Similarly, animals given specific anti-rAce Igs were less likely to develop E. faecalis endocarditis (P = 0.0001) and showed fewer CFU in vegetations (P = 0.0146). In conclusion, we have shown for the first time that Ace is involved in pathogenesis of, and is useful for protection against, E. faecalis experimental endocarditis

Predictors of Medication Adherence and Blood Pressure Control among Saudi Hypertensive Patients Attending Primary Care Clinics: A Cross-Sectional Study

Purpose To assess the level of medication adherence and to investigate predictors of medication adherence and blood pressure control among hypertensive patients attending primary healthcare clinics in Makkah, Saudi Arabia. Patients and methods Hypertensive patients meeting the eligibility criteria were recruited from eight primary care clinics between January and May 2016 for this study. The patients completed Arabic version of Morisky Medication Adherence Scale (MMAS-8), an eight-item validated, self-reported measure to assess medication adherence. A structured data collection form was used to record patients’ sociodemographic, medical and medication data. Results Two hundred and four patients, of which 71.6% were females, participated in the study. Patients’ mean age was 59.1 (SD 12.2). The mean number of medication used by patients was 4.4 (SD 1.89). More than half (110; 54%) of the patients were non-adherent to their medications (MMAS score 65 years (OR 2.0 [95% CI: 1.0–4.2; P = 0.04]), and being diabetic (OR 0.25 [95% CI: 0.1–0.6; P = 0.04]) were found to be independent predictors of medication adherence. Conclusion Medication adherence is alarmingly low among hypertensive patients attending primary care clinics in Saudi Arabia which may partly explain observed poor blood pressure control. There is a clear need to educate patients about the importance of medication adherence and its impact on improving clinical outcomes. Future research should identify barriers to medication adherence among Saudi hypertensive patients

Protocol for the immediate delivery versus expectant care of women with preterm prelabour rupture of the membranes close to term (PPROMT) Trial [ISRCTN44485060]

BACKGROUND: Preterm prelabour rupture of membranes (PPROM) complicates up to 2% of all pregnancies and is the cause of 40% of all preterm births. The optimal management of women with PPROM prior to 37 weeks, is not known. Furthermore, diversity in current clinical practice suggests uncertainty about the appropriate clinical management. There are two options for managing PPROM, expectant management (a wait and see approach) or early planned birth. Infection is the main risk for women in which management is expectant. This risk need to be balanced against the risk of iatrogenic prematurity if early delivery is planned. The different treatment options may also have different health care costs. Expectant management results in prolonged antenatal hospitalisation while planned early delivery may necessitate intensive care of the neonate for problems associated with prematurity. METHODS/DESIGN: We aim to evaluate the effectiveness of early planned birth compared with expectant management for women with PPROM between 34 weeks and 36(6 )weeks gestation, in a randomised controlled trial. A secondary aim is a cost analysis to establish the economic impact of the two treatment options and establish the treatment preferences of women with PPROM close to term. The early planned birth group will be delivered within 24 hours according to local management protocols. In the expectant management group birth will occur after spontaneous labour, at term or when the attending clinician feels that birth is indicated according to usual care. Approximately 1812 women with PPROM at 34–36(6 )weeks gestation will be recruited for the trial. The primary outcome of the study is neonatal sepsis. Secondary infant outcomes include respiratory distress, perinatal mortality, neonatal intensive care unit admission, assisted ventilation and early infant development. Secondary maternal outcomes include chorioamnionitis, postpartum infection treated with antibiotics, antepartum haemorrhage, induction of labour, mode of delivery, maternal satisfaction with care, duration of hospitalisation, and maternal wellbeing at four months postpartum. DISCUSSION: This trial will provide evidence on the optimal care for women with PPROM close to term (34–37 weeks gestation). Consideration of both the clinical and economic sequelae of the management of PPROM will enable informed decision making and guideline development