Helium-oxygen reduces the production of carbon dioxide during weaning from mechanical ventilation

<p>Abstract</p> <p>Background</p> <p>Prolonged weaning from mechanical ventilation has a major impact on ICU bed occupancy and patient outcome, and has significant cost implications.</p> <p>There is evidence in patients around the period of extubation that helium-oxygen leads to a reduction in the work of breathing. Therefore breathing helium-oxygen during weaning may be a useful adjunct to facilitate weaning. We hypothesised that breathing helium-oxygen would reduce carbon dioxide production during the weaning phase of mechanical ventilation.</p> <p>Materials/patients and methods</p> <p>We performed a prospective randomised controlled single blinded cross-over trial on 19 adult intensive care patients without significant airways disease who fulfilled criteria for weaning with CPAP. Patients were randomised to helium-oxygen and air-oxygen delivered during a 2 hour period of CPAP ventilation. Carbon dioxide production (VCO₂) was measured using a near patient main stream infrared carbon dioxide sensor and fixed orifice pneumotachograph.</p> <p>Results</p> <p>Compared to air-oxygen, helium-oxygen significantly decreased VCO₂production at the end of the 2 hour period of CPAP ventilation; there was a mean difference in CO₂production of 48.9 ml/min (95% CI 18.7-79.2 p = 0.003) between the groups. There were no significant differences in other respiratory and haemodynamic parameters.</p> <p>Conclusion</p> <p>This study shows that breathing a helium-oxygen mixture during weaning reduces carbon dioxide production. This physiological study supports the need for a clinical trial of helium-oxygen mixture during the weaning phase of mechanical ventilation with duration of weaning as the primary outcome.</p> <p>Trial registration</p> <p>ISRCTN56470948</p

A study of the perceived risks, benefits and barriers to the use of SDD in adult critical care units (the SuDDICU study)

Peer reviewedPublisher PD

Comparison of vaginal microbiota sampling techniques: Cytobrush versus swab

© 2017 The Author(s). Evidence suggests the vaginal microbiota (VM) may influence risk of persistent Human Papillomavirus (HPV) infection and cervical carcinogenesis. Established cytology biobanks, typically collected with a cytobrush, constitute a unique resource to study such associations longitudinally. It is plausible that compared to rayon swabs; the most commonly used sampling devices, cytobrushes may disrupt biofilms leading to variation in VM composition. Cervico-vaginal samples were collected with cytobrush and rayon swabs from 30 women with high-grade cervical precancer. Quantitative PCR was used to compare bacterial load and Illumina MiSeq sequencing of the V1-V3 regions of the 16S rRNA gene used to compare VM composition. Cytobrushes collected a higher total bacterial load. Relative abundance of bacterial species was highly comparable between sampling devices (R 2 = 0.993). However, in women with a Lactobacillus-depleted, high-diversity VM, significantly less correlation in relative species abundance was observed between devices when compared to those with a Lactobacillus species-dominant VM (p = 0.0049). Cytobrush and swab sampling provide a comparable VM composition. In a small proportion of cases the cytobrush was able to detect underlying high-diversity community structure, not realized with swab sampling. This study highlights the need to consider sampling devices as potential confounders when comparing multiple studies and datasets

Quality of Care in Humanitarian Surgery

Humanitarian surgical programs are set up de novo, within days or hours in emergency or disaster settings. In such circumstances, insuring quality of care is extremely challenging. Basic structural inputs such as a safe structure, electricity, clean water, a blood bank, sterilization equipment, a post-anesthesia recovery unit, appropriate medications should be established. Currently, no specific credentials are needed for surgeons to operate in a humanitarian setting; the training of more humanitarian surgeons is desperately needed. Standard perioperative protocols for the humanitarian setting after common procedures such as Cesarean section, burn care, open fractures, and amputations and antibiotic prophylaxis, and post-operative pain management must be developed. Outcome data, especially long-term outcomes, are difficult to collect as patients often do not return for follow-up and may be difficult to trace; standard databases for post-operative infections and mortality rates should be established. Checklists have recently received significant attention as an instrument to support the improvement of surgical quality; knowing which items are most applicable to humanitarian settings remains unknown. In conclusion, the quality of surgical services in humanitarian settings must be regulated. Many other core medical activities of humanitarian organizations such as therapeutic feeding, mass vaccination, and the treatment of infectious diseases, such as tuberculosis and human immunodeficiency virus, are subject to rigorous reporting of quality indicators. There is no reason why surgery should be exempted from quality oversight. The surgical humanitarian community should pull together before the next disaster strikes

Characterisation of Human Embryonic Stem Cells Conditioning Media by 1H-Nuclear Magnetic Resonance Spectroscopy

BACKGROUND: Cell culture media conditioned by human foreskin fibroblasts (HFFs) provide a complex supplement of protein and metabolic factors that support in vitro proliferation of human embryonic stem cells (hESCs). However, the conditioning process is variable with different media batches often exhibiting differing capacities to maintain hESCs in culture. While recent studies have examined the protein complement of conditioned culture media, detailed information regarding the metabolic component of this media is lacking. METHODOLOGY/PRINCIPAL FINDINGS: Using a (1)H-Nuclear Magnetic Resonance ((1)H-NMR) metabonomics approach, 32 metabolites and small compounds were identified and quantified in media conditioned by passage 11 HFFs (CMp11). A number of metabolites were secreted by HFFs with significantly higher concentration of lactate, alanine, and formate detected in CMp11 compared to non-conditioned media. In contrast, levels of tryptophan, folate and niacinamide were depleted in CMp11 indicating the utilisation of these metabolites by HFFs. Multivariate statistical analysis of the (1)H-NMR data revealed marked age-related differences in the metabolic profile of CMp11 collected from HFFs every 24 h over 72 h. Additionally, the metabolic profile of CMp11 was altered following freezing at -20°C for 2 weeks. CM derived from passage 18 HFFs (CMp18) was found to be ineffective at supporting hESCs in an undifferentiated state beyond 5 days culture. Multivariate statistical comparison of CMp11 and CMp18 metabolic profiles enabled rapid and clear discrimination between the two media with CMp18 containing lower concentrations of lactate and alanine as well as higher concentrations of glucose and glutamine. CONCLUSIONS/SIGNIFICANCE: (1)H-NMR-based metabonomics offers a rapid and accurate method of characterising hESC conditioning media and is a valuable tool for monitoring, controlling and optimising hESC culture media preparation

VgrG and PAAR Proteins Define Distinct Versions of a Functional Type VI Secretion System

The Type VI secretion system (T6SS) is widespread among bacterial pathogens and acts as an effective weapon against competitor bacteria and eukaryotic hosts by delivering toxic effector proteins directly into target cells. The T6SS utilises a bacteriophage-like contractile machinery to expel a puncturing device based on a tube of Hcp topped with a VgrG spike, which can be extended by a final tip from a PAAR domain-containing protein. Effector proteins are believed to be delivered by specifically associating with particular Hcp, VgrG or PAAR proteins, either covalently ('specialised') or non-covalently ('cargo' effectors). Here we used the T6SS of the opportunistic pathogen Serratia marcescens, together with integratecd genetic, proteomic and biochemical approaches, to elucidate the role of specific VgrG and PAAR homologues in T6SS function and effector specificity, revealing new aspects and unexpected subtleties in effector delivery by the T6SS. We identified effectors, both cargo and specialised, absolutely dependent on a particular VgrG for delivery to target cells, and discovered that other cargo effectors can show a preference for a particular VgrG. The presence of at least one PAAR protein was found to be essential for T6SS function, consistent with designation as a 'core' T6SS component. We showed that specific VgrG-PAAR combinations are required to assemble a functional T6SS and that the three distinct VgrG-PAAR assemblies in S. marcescens exhibit distinct effector specificity and efficiency. Unexpectedly, we discovered that two different PAAR-containing Rhs proteins can functionally pair with the same VgrG protein. Showing that accessory EagR proteins are involved in these interactions, native VgrG-Rhs-EagR complexes were isolated and specific interactions between EagR and cognate Rhs proteins identified. This study defines an essential yet flexible role for PAAR proteins in the T6SS and highlights the existence of distinct versions of the machinery with differential effector specificity and efficiency of target cell delivery

Women’s health and well-being in low-income formal and informal neighbourhoods on the eve of the armed conflict in Aleppo

Objectives To explore how married women living in low-income formal and informal neighbourhoods in Aleppo, Syria, perceived the effects of neighbourhood on their health and well-being, and the relevance of these findings to future urban rebuilding policies post-conflict. Methods Semi-structured interviews were undertaken with eighteen married women living in informal or socioeconomically disadvantaged formal neighbourhoods in Aleppo in 2011, a year before the armed conflict caused massive destruction in all these neighbourhoods. Results Our findings suggest that the experience of neighbourhood social characteristics is even more critical to women’s sense of well-being than environmental conditions and physical infrastructure. Most prominent was the positive influence of social support on well-being. Conclusions The significance of this study lies, first, in its timing, before the widespread destruction of both formal and informal neighbourhoods in Aleppo and, second, and in its indication of the views of women who lived in marginalised communities on what neighbourhood characteristics mattered to them. Further research post-conflict needs to explore how decisions on urban rebuilding are made and their likely influence on health and well-being

Constitutive Type VI Secretion System Expression Gives Vibrio cholerae Intra- and Interspecific Competitive Advantages

The type VI secretion system (T6SS) mediates protein translocation across the cell membrane of Gram-negative bacteria, including Vibrio cholerae – the causative agent of cholera. All V. cholerae strains examined to date harbor gene clusters encoding a T6SS. Structural similarity and sequence homology between components of the T6SS and the T4 bacteriophage cell-puncturing device suggest that the T6SS functions as a contractile molecular syringe to inject effector molecules into prokaryotic and eukaryotic target cells. Regulation of the T6SS is critical. A subset of V. cholerae strains, including the clinical O37 serogroup strain V52, express T6SS constitutively. In contrast, pandemic strains impose tight control that can be genetically disrupted: mutations in the quorum sensing gene luxO and the newly described regulator gene tsrA lead to constitutive T6SS expression in the El Tor strain C6706. In this report, we examined environmental V. cholerae isolates from the Rio Grande with regard to T6SS regulation. Rough V. cholerae lacking O-antigen carried a nonsense mutation in the gene encoding the global T6SS regulator VasH and did not display virulent behavior towards Escherichia coli and other environmental bacteria. In contrast, smooth V. cholerae strains engaged constitutively in type VI-mediated secretion and displayed virulence towards prokaryotes (E. coli and other environmental bacteria) and a eukaryote (the social amoeba Dictyostelium discoideum). Furthermore, smooth V. cholerae strains were able to outcompete each other in a T6SS-dependent manner. The work presented here suggests that constitutive T6SS expression provides V. cholerae with an advantage in intraspecific and interspecific competition.Canadian Institutes of Health Research (Operating Grant MOP-84473)Alberta Heritage Foundation for Medical Research (Alberta Innovates-Health Solutions, Endowment Fund)National Institutes of Health (U.S.) (grant MD001091-01)National Institutes of Health (U.S.) (grant GM068855-02)Olegario V. Rana FellowshipAlberta Heritage Foundation for Medical Research (Alberta Innovates-Health Solutions Graduate Studentships

Light Variability Illuminates Niche-Partitioning among Marine Picocyanobacteria

Prochlorococcus and Synechococcus picocyanobacteria are dominant contributors to marine primary production over large areas of the ocean. Phytoplankton cells are entrained in the water column and are thus often exposed to rapid changes in irradiance within the upper mixed layer of the ocean. An upward fluctuation in irradiance can result in photosystem II photoinactivation exceeding counteracting repair rates through protein turnover, thereby leading to net photoinhibition of primary productivity, and potentially cell death. Here we show that the effective cross-section for photosystem II photoinactivation is conserved across the picocyanobacteria, but that their photosystem II repair capacity and protein-specific photosystem II light capture are negatively correlated and vary widely across the strains. The differences in repair rate correspond to the light and nutrient conditions that characterize the site of origin of the Prochlorococcus and Synechococcus isolates, and determine the upward fluctuation in irradiance they can tolerate, indicating that photoinhibition due to transient high-light exposure influences their distribution in the ocean