Membership and behavior of ultra-low-diversity pathogen communities present in the gut of humans during prolonged critical illness.

UnlabelledWe analyzed the 16S rRNA amplicon composition in fecal samples of selected patients during their prolonged stay in an intensive care unit (ICU) and observed the emergence of ultra-low-diversity communities (1 to 4 bacterial taxa) in 30% of the patients. Bacteria associated with the genera Enterococcus and Staphylococcus and the family Enterobacteriaceae comprised the majority of these communities. The composition of cultured species from stool samples correlated to the 16S rRNA analysis and additionally revealed the emergence of Candida albicans and Candida glabrata in ~75% of cases. Four of 14 ICU patients harbored 2-member pathogen communities consisting of one Candida taxon and one bacterial taxon. Bacterial members displayed a high degree of resistance to multiple antibiotics. The virulence potential of the 2-member communities was examined in C. elegans during nutrient deprivation and exposure to opioids in order to mimic local conditions in the gut during critical illness. Under conditions of nutrient deprivation, the bacterial members attenuated the virulence of fungal members, leading to a "commensal lifestyle." However, exposure to opioids led to a breakdown in this commensalism in 2 of the ultra-low-diversity communities. Application of a novel antivirulence agent (phosphate-polyethylene glycol [Pi-PEG]) that creates local phosphate abundance prevented opioid-induced virulence among these pathogen communities, thus rescuing the commensal lifestyle. To conclude, the gut microflora in critically ill patients can consist of ultra-low-diversity communities of multidrug-resistant pathogenic microbes. Local environmental conditions in gut may direct pathogen communities to adapt to either a commensal style or a pathogenic style.ImportanceDuring critical illness, the normal gut microbiota becomes disrupted in response to host physiologic stress and antibiotic treatment. Here we demonstrate that the community structure of the gut microbiota during prolonged critical illness is dramatically changed such that in many cases only two-member pathogen communities remain. Most of these ultra-low-membership communities display low virulence when grouped together (i.e., a commensal lifestyle); individually, however, they can express highly harmful behaviors (i.e., a pathogenic lifestyle). The commensal lifestyle of the whole community can be shifted to a pathogenic one in response to host factors such as opioids that are released during physiologic stress and critical illness. This shift can be prevented by using compounds such as Pi-PEG15-20 that interrupt bacterial virulence expression. Taking the data together, this report characterizes the plasticity seen with respect to the choice between a commensal lifestyle and a pathogenic lifestyle among ultra-low-diversity pathogen communities that predominate in the gut during critical illness and offers novel strategies for prevention of sepsis

A subsurface particle maximum layer and enhanced microbial activity in the secondary nitrite maximum of the northeastern tropical Pacific Ocean

Profiles of light transmission, dissolved oxygen, dissolved nutrients, electron transport system (ETS) activity, temperature and salinity were made in the northeastern tropical Pacific Ocean. A particle maximum at 150–300 m within the oxygen minimum and secondary nitrite maximum was associated with the salinity maximum of Subtropical Subsurface Water. A subsurface maximum in ETS activity was also found to be associated with the secondary nitrite maximum and the particle maximum. Persistence of these features at a constant depth and their location within a minimum in vertical static stability suggest an advective and/or in situ origin for the particles and an in situ development of the associated chemical and biochemical extremes

A quality improvement project to increase self-administration of medicines in an acute hospital

Quality problem or issue A patient survey found significantly fewer patients reported they had self-administered their medicines while in hospital (20% of 100 patients) than reported that they would like to (44% of 100). We aimed to make self-administration more easily available to patients who wanted it. Initial assessment We conducted a failure, modes and effects analysis, collected baseline data on four wards and carried out observations. Choice of solution Our initial assessment suggested that the main areas we should focus on were raising patient awareness of self-administration, changing the patient assessment process and creating a storage solution for medicines being self-administered. We developed new patient information leaflets and posters and a doctor’s assessment form using Plan–Do–Study–Act cycles. We developed initial designs for a storage solution. Implementation We piloted the new materials on three wards; the fourth withdrew due to staff shortages. Evaluation Following collection of baseline data, we continued to collect weekly data. We found that the proportion of patients who wished to self-administer who reported that they were able to do so, significantly increased from 41% (of 155 patients) to 66% (of 118 patients) during the study, despite a period when the hospital was over capacity. Lessons learned Raising and maintaining healthcare professionals’ awareness of self-administration can greatly increase the proportion of patients who wish to self-administer who actually do so. Healthcare professionals prefer multi-disciplinary input into the assessment process

Bone disease in patients with primary sclerosing cholangitis.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fiel

Relationship among research collaboration, number of documents and number of citations. A case study in Spanish computer science production in 2000-2009.

This paper analyzes the relationship among research collaboration, number of documents and number of citations of computer science research activity. It analyzes the number of documents and citations and how they vary by number of authors. They are also analyzed (according to author set cardinality) under different circumstances, that is, when documents are written in different types of collaboration, when documents are published in different document types, when documents are published in different computer science subdisciplines, and, finally, when documents are published by journals with different impact factor quartiles. To investigate the above relationships, this paper analyzes the publications listed in the Web of Science and produced by active Spanish university professors between 2000 and 2009, working in the computer science field. Analyzing all documents, we show that the highest percentage of documents are published by three authors, whereas single-authored documents account for the lowest percentage. By number of citations, there is no positive association between the author cardinality and citation impact. Statistical tests show that documents written by two authors receive more citations per document and year than documents published by more authors. In contrast, results do not show statistically significant differences between documents published by two authors and one author. The research findings suggest that international collaboration results on average in publications with higher citation rates than national and institutional collaborations. We also find differences regarding citation rates between journals and conferences, across different computer science subdisciplines and journal quartiles as expected. Finally, our impression is that the collaborative level (number of authors per document) will increase in the coming years, and documents published by three or four authors will be the trend in computer science literature

Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity.

Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans1-3. Recently, ADCY3 (adenylyl cyclase 3) gene mutations have been implicated in obesity4,5. ADCY3 localizes to the primary cilia of neurons 6 , organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases in which obesity is a cardinal manifestation 7 . We demonstrate that MC4R colocalizes with ADCY3 at the primary cilia of a subset of hypothalamic neurons, that obesity-associated MC4R mutations impair ciliary localization and that inhibition of adenylyl cyclase signaling at the primary cilia of these neurons increases body weight. These data suggest that impaired signaling from the primary cilia of MC4R neurons is a common pathway underlying genetic causes of obesity in humans

Ongoing under-reporting of clinically relevant safety data in phase II studies of tyrosine kinase inhibitors

status: publishe

Medicines management at home during the COVID-19 pandemic: a qualitative study exploring the UK patient/carer perspective

OBJECTIVES: To explore home medicine practices and safety for people shielding and/or over the age of 70 during the COVID-19 pandemic and to create guidance, from the patient/carer perspective, for enabling safe medicine practices for this population. METHODS: Semi-structured interviews were carried out with 50 UK participants who were shielding and/or over the age of 70 and who used medicines for a long-term condition, using telephone or video conferencing. Participants were recruited through personal/professional networks and through patient/carer organisations. Participants were asked about their experiences of managing medicines during the pandemic and how this differed from previous practices. Data were analysed using inductive thematic analysis. KEY FINDINGS: Patients' and their families' experiences of managing medicines safely during the pandemic varied greatly. Analysis suggests that this was based on the patient's own agency, the functioning of their medicines system pre-pandemic and their relationships with family, friends, community networks and pharmacy staff. Medicine safety issues reported included omitted doses and less-effective formulations being used. Participants also described experiencing high levels of anxiety related to obtaining medicines, monitoring medicines and feeling at risk of contracting COVID-19 while accessing healthcare services for medicine-related issues. Effects of the pandemic on medicines adherence were reported to be positive by some and negative by others. CONCLUSIONS: Pharmacy staff have a key role to play by establishing good relationships with patients and their families, working with prescribers to ensure medicines systems are as joined up as possible, and signposting to community networks that can help with medicines collection