Bioinformatics characterization of BcsA-like orphan proteins suggest they form a novel family of pseudomonad cyclic-β-glucan synthases

Bacteria produce a variety of polysaccharides with functional roles in cell surface coating, surface and host interactions, and biofilms. We have identified an ‘Orphan’ bacterial cellulose synthase catalytic subunit (BcsA)-like protein found in four model pseudomonads, P. aeruginosa PA01, P. fluorescens SBW25, P. putida KT2440 and P. syringae pv. tomato DC3000. Pairwise alignments indicated that the Orphan and BcsA proteins shared less than 41% sequence identity suggesting they may not have the same structural folds or function. We identified 112 Orphans among soil and plant-associated pseudomonads as well as in phytopathogenic and human opportunistic pathogenic strains. The wide distribution of these highly conserved proteins suggest they form a novel family of synthases producing a different polysaccharide. In silico analysis, including sequence comparisons, secondary structure and topology predictions, and protein structural modelling, revealed a two-domain transmembrane ovoid-like structure for the Orphan protein with a periplasmic glycosyl hydrolase family GH17 domain linked via a transmembrane region to a cytoplasmic glycosyltransferase family GT2 domain. We suggest the GT2 domain synthesises β-(1,3)-glucan that is transferred to the GH17 domain where it is cleaved and cyclised to produce cyclic-β-(1,3)-glucan (CβG). Our structural models are consistent with enzymatic characterisation and recent molecular simulations of the PaPA01 and PpKT2440 GH17 domains. It also provides a functional explanation linking PaPAK and PaPA14 Orphan (also known as NdvB) transposon mutants with CβG production and biofilm-associated antibiotic resistance. Importantly, cyclic glucans are also involved in osmoregulation, plant infection and induced systemic suppression, and our findings suggest this novel family of CβG synthases may provide similar range of adaptive responses for pseudomonads.<br/

Evaluating implementation of methicillin-resistant Staphylococcus aureus (MRSA) prevention guidelines in spinal cord injury centers using the PARIHS framework: a mixed methods study

BACKGROUND: To prevent methicillin-resistant Staphylococcus aureus (MRSA) in Spinal Cord Injury and Disorder (SCI/D) Centers, the Guidelines for Implementation of MRSA Prevention Initiative in the Spinal Cord Injury Centers were released in July 2008 in the Veterans Affairs (VA) Health Care System. The purpose of this study was to use the Promoting Action on Research Implementation in Health Systems (PARiHS) framework to evaluate the experiences of implementation of SCI/D MRSA prevention guidelines in VA SCI/D Centers approximately 2-3 years after the guidelines were released. METHODS: Mixed methods were used across two phases in this study. The first phase included an anonymous, web-based cross-sectional survey administered to providers at all 24 VA SCI/D Centers. The second phase included semi-structured telephone interviews with providers at 9 SCI/D Centers. The PARiHS framework was used as the foundation of both the survey questions and semi-structured interview guide. RESULTS: The survey was completed by 295 SCI/D providers (43.8 % response rate) from 22 of the 24 SCI/D Centers (91.7 % participation rate). Respondents included nurses (57.3 %), therapists (24.4 %), physicians (11.1 %), physician assistants (3.4 %), and other health care professionals (3.8 %). Approximately 36 % of the SCI/D providers surveyed had not seen, did not remember seeing, or had never heard of the MRSA SCI/D guidelines, whereas 42.3 % of providers reported that the MRSA SCI/D guidelines were fully implemented in their SCI/D Center. Data revealed numerous barriers and facilitators to guideline implementation. Facilitators included enhanced leadership support and provider education, focused guideline dissemination to reach SCI/D providers, and strong perceived evidence supporting the guidelines. Barriers included lack of awareness of the guidelines among physical therapists and physician assistants and challenges in cohorting/isolating MRSA-positive patients and following contact precautions. CONCLUSIONS: Successful implementation of MRSA infection prevention guidelines in SCI/D settings requires (1) guideline dissemination that reaches the full range of SCI/D providers working in inpatient, outpatient, and other care settings, (2) provider education that is frequent and systematic, (3) strong leadership support, and (4) that barriers unique to the recommendations are addressed. These findings may be used to inform selection of implementation strategies and optimize infection prevention beyond MRSA as well as in other specialty care populations

Appropriate and inappropriate relationship: David's story

Table of study survey and interview questions mapped to PARiHS elements and sub-elements. Survey and interview questions mapped to the PARiHS framework elements and sub-elements

Developing standardized patient-based cases for communication training: lessons learned from training residents to communicate diagnostic uncertainty.

Health professions education has benefitted from standardized patient (SP) programs to develop and refine communication and interpersonal skills in trainees. Effective case design is essential to ensure an SP encounter successfully meets learning objectives that are focused on communication skills. Creative, well-designed case scenarios offer learners the opportunity to engage in complex patient encounters, while challenging them to address the personal and emotional contexts in which their patients are situated. Therefore, prior to considering the practical execution of the patient encounter, educators will first need a clear and structured strategy for writing, organizing, and developing cases. The authors reflect on lessons learned in developing standardized patient-based cases to train learners to communicate to patients during times of diagnostic uncertainty, and provide suggestions to develop a set of simulation cases that are both standardized and diverse. Key steps and workflow processes that can assist educators with case design are introduced. The authors review the need to increase awareness of and mitigate existing norms and implicit biases, while maximizing variation in patient diversity. Opportunities to leverage the breadth of emotional dispositions of the SP and the affective domain of a clinical encounter are also discussed as a means to guide future case development and maximize the value of a case for its respective learning outcomes

Development of the Uncertainty Communication Checklist: A Patient-Centered Approach to Patient Discharge From the Emergency Department

Clear communication with patients upon emergency department (ED) discharge is important for patient safety during the transition to outpatient care. Over one-third of patients are discharged from the ED with diagnostic uncertainty, yet there is no established approach for effective discharge communication in this scenario. From 2017 to 2019, the authors developed the Uncertainty Communication Checklist for use in simulation-based training and assessment of emergency physician communication skills when discharging patients with diagnostic uncertainty. This development process followed the established 12-step Checklist Development Checklist framework and integrated patient feedback into 6 of the 12 steps. Patient input was included as it has potential to improve patient-centeredness of checklists related to assessment of clinical performance. Focus group patient participants from 2 clinical sites were included: Thomas Jefferson University Hospital, Philadelphia, PA, and Northwestern University Hospital, Chicago, Illinois. The authors developed a preliminary instrument based on existing checklists, clinical experience, literature review, and input from an expert panel comprising health care professionals and patient advocates. They then refined the instrument based on feedback from 2 waves of patient focus groups, resulting in a final 21-item checklist. The checklist items assess if uncertainty was addressed in each step of the discharge communication, including the following major categories: introduction, test results/ED summary, no/uncertain diagnosis, next steps/follow-up, home care, reasons to return, and general communication skills. Patient input influenced both what items were included and the wording of items in the final checklist. This patient-centered, systematic approach to checklist development is built upon the rigor of the Checklist Development Checklist and provides an illustration of how to integrate patient feedback into the design of assessment tools when appropriate

I Don\u27t Have a Diagnosis for You: Preparing Medical Students to Communicate Diagnostic Uncertainty in the Emergency Department

Introduction: Diagnostic uncertainty abounds in medicine, and communication of that uncertainty is critical to the delivery of high-quality patient care. While there has been training in communicating diagnostic uncertainty directed towards residents, a gap remains in preparing medical students to understand and communicate diagnostic uncertainty. We developed a session to introduce medical students to diagnostic uncertainty and to practice communicating uncertainty using a checklist during role-play patient conversations. Methods: This virtual session was conducted for third-year medical students at the conclusion of their core clerkships. It consisted of prework, didactic lecture, peer role-play, and debriefing. The prework included reflection prompts and an interactive online module. The role-play featured a patient complaining of abdominal pain being discharged from the emergency department without a confirmed diagnosis. Students participated in the role of patient, provider, or observer. Results: Data from an anonymous postsession survey (76% response rate; 202 of 265 students) indicated that most students (82%; 152 of 185) felt more comfortable communicating diagnostic uncertainty after the session. A majority (83%; 166 of 201) indicated the session was useful, and most (81%; 149 of 184) indicated it should be included in the curriculum. Discussion: This virtual session requires few facilitators; has peer role-play, eliminating the need for standardized patients; and is adaptable for in-person teaching. As its goal was to introduce an approach to communicating diagnostic uncertainty, not achieve mastery, students were not individually assessed for proficiency using the Uncertainty Communication Checklist. Students felt the session intervention was valuable

Simulation-based mastery learning compared to standard education for discussing diagnostic uncertainty with patients in the emergency department: a randomized controlled trial.

BACKGROUND: Diagnostic uncertainty occurs frequently in emergency medical care, with more than one-third of patients leaving the emergency department (ED) without a clear diagnosis. Despite this frequency, ED providers are not adequately trained on how to discuss diagnostic uncertainty with these patients, who often leave the ED confused and concerned. To address this training need, we developed the Uncertainty Communication Education Module (UCEM) to teach physicians how to discuss diagnostic uncertainty. The purpose of the study is to evaluate the effectiveness of the UCEM in improving physician communications. METHODS: The trial is a multicenter, two-arm randomized controlled trial designed to teach communication skills using simulation-based mastery learning (SBML). Resident emergency physicians from two training programs will be randomly assigned to immediate or delayed receipt of the two-part UCEM intervention after completing a baseline standardized patient encounter. The two UCEM components are: 1) a web-based interactive module, and 2) a smart-phone-based game. Both formats teach and reinforce communication skills for patient cases involving diagnostic uncertainty. Following baseline testing, participants in the immediate intervention arm will complete a remote deliberate practice session via a video platform and subsequently return for a second study visit to assess if they have achieved mastery. Participants in the delayed intervention arm will receive access to UCEM and remote deliberate practice after the second study visit. The primary outcome of interest is the proportion of residents in the immediate intervention arm who achieve mastery at the second study visit. DISCUSSION: Patients\u27 understanding of the care they received has implications for care quality, safety, and patient satisfaction, especially when they are discharged without a definitive diagnosis. Developing a patient-centered diagnostic uncertainty communication strategy will improve safety of acute care discharges. Although use of SBML is a resource intensive educational approach, this trial has been deliberately designed to have a low-resource, scalable intervention that would allow for widespread dissemination and uptake. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (NCT04021771). Registration date: July 16, 2019

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions