AFM Force Mapping Elucidates Pilus Deployment and Key Lifestyle-Dependent Surface Properties in Bdellovibrio bacteriovorus.

Bdellovibrio bacteriovorus is known for predation of a wide variety of Gram-negative bacteria, making it of interest as an alternative or supplement to chemical antibiotics. However, a fraction of B. bacteriovorus follows a nonpredatory, "host-independent" (HI) life cycle. In this study, live predatory and HI B. bacteriovorus were captured on a surface and examined, in buffer, by collecting force maps using atomic force microscopy (AFM). The approach curves obtained on HI cells are similar to those on other Gram-negative cells, with a short nonlinear region followed by a linear region. In contrast, the approach curves obtained on predatory cells have a large nonlinear region, reflecting the unusual flexibility of the predatory cell. As the AFM tip is retracted, it shows virtually no adhesion to predatory B. bacteriovorus but has multiple adhesion events on HI cells and the 200-500+ nm region immediately surrounding them. Measured pull-off forces, pull-off distances, and effective spring constants are consistent with the multiple stretching events of Type IV pili, both on and especially adjacent to the cells. Exposure of the HI B. bacteriovorus to a pH-neutral 10% cranberry juice solution, which contains type A proanthocyanidins that are known to interfere with the adhesion of multiple types of pili, results in a substantial reduction in adhesion. Type IV pili are required for successful predation by B. bacteriovorus, but pili used in the predation process are located at the non-flagellated pole of the cell and can retract when not in use. Such pili are rarely observed under the conditions of this study, where the predator has not encountered a prey cell. In contrast, HI cells appear to have many pili distributed on and around the whole cell, presumably ready to be utilized for a variety of HI cell activities including attachment to surfaces.

What are we missing? The quality of intraoperative handover before and after introduction of a checklist.

PURPOSE: Intraoperative handovers are common in anesthesia practice and are associated with increased patient morbidity and mortality. Checklists may improve transfer of information during handovers. This before-and-after study sought to examine the effect of a checklist on intraoperative handover. We hypothesized that introducing a handover checklist would improve our primary outcome of completeness of data transfer. METHODS: From February to August 2016, anesthesia providers (residents, fellows, and consultants) at a single tertiary academic center participated in a handover study. Baseline handovers between anesthesia care providers were videotaped, analyzed, and compared with anesthetic records. An intraoperative handover checklist was then introduced, and handovers completed with it were videotaped. The completeness of handovers was compared between the baseline routine and checklist groups. The primary outcome was completeness of information transfer. RESULTS: Sixty-seven anesthesia providers participated in the study. Use of the intraoperative handover checklist improved completeness of handover by 6% (95% confidence interval [CI], 2 to 10; P < 0.01). There was no relationship observed between the provider (consultants/fellows vs resident) of the handovers and the degree of completeness (95% CI, 3 to 8; P = 0.33). Complexity had a significant impact on the handover completeness with low or high complexity cases more completely handed over than those of medium complexity both before and after the intervention-a 6% increase for low complexity (95% CI, 1 to 11; P = 0.02) and a 9% increase for high complexity (95% CI, 3 to 14; P < 0.01). CONCLUSION: Use of a checklist during intraoperative handovers improved completeness of data transfer. Handover checklists should be considered to improve handover completeness.

RéSUMé: OBJECTIF: Les transferts peropératoires sont fréquents dans la pratique de l'anesthésie et sont associés à une augmentation de la morbidité et de la mortalité des patients. Les listes de vérification pourraient améliorer le transfert d'informations pendant les transitions. Cette étude avant-après a cherché à examiner l'effet d'une liste de vérification sur les transferts peropératoires. Nous avons émis l'hypothèse que l'introduction d'une liste de vérification de transfert améliorerait notre critère d'évaluation principal, nommément la complétude du transfert des informations. MéTHODE: De février à août 2016, des prestataires d'anesthésie (résidents, fellows et consultants) d'un seul centre universitaire tertiaire ont participé à une étude sur les transferts. Les transferts de base entre les fournisseurs de soins d'anesthésie ont été filmés, analysés et comparés aux dossiers d'anesthésie. Une liste de contrôle de transfert peropératoire a ensuite été introduite, et les transferts réalisés avec celle-ci ont été filmés. La complétude des transferts a été comparée entre les groupes faisant un transfert normal de base et ceux utilisant la liste de vérification. Le critère d'évaluation principal était la complétude du transfert d'informations. RéSULTATS: Soixante-sept fournisseurs d'anesthésie ont participé à l'étude. L'utilisation de la liste de vérification de transfert peropératoire a amélioré la complétude du transfert de 6 % (intervalle de confiance [IC] à 95 %, 2 à 10; P < 0,01). Aucune relation n'a été observée entre le fournisseur (consultants/fellows) vs résidents) responsable des transferts et le degré de complétude du transfert (IC 95 %, 3 à 8; P = 0,33). La complexité a eu un impact significatif sur la complétude du transfert, les cas de basse ou haute complexité étant transférés de manière plus complète que les cas de complexité moyenne, tant avant qu'après l'intervention ­ avec une augmentation de 6 % pour les cas de faible complexité (IC 95 %, 1 à 11; P = 0,02) et une augmentation de 9 % pour les cas de complexité élevée (IC 95 %, 3 à 14; P < 0,01). CONCLUSION: L'utilisation d'une liste de vérification lors des transferts peropératoires a amélioré la complétude du transfert des informations. Les listes de vérification de transfert devraient être envisagées pour améliorer la complétude des transferts.

Platelet Src family kinases: A tale of reversible phosphorylation.

Sarcoma (Src) family kinases (SFKs) have occupied a central place in platelet research for over 40 years. Discovered by virologists and oncologists as the proto proto-oncogene, Src tyrosine kinase spurred a phenomenal burst of research on reversible tyrosine phosphorylation and signal transduction. For a time, platelets were adopted as the model of choice for studying the biological functions of Src, owing to their ease of isolation, high Src expression, and lack of a nucleus, only to be abandoned due to challenges of culturing and manipulating using common molecular biology-based techniques. For platelet biologists, SFKs have remained an important area of investigation, initiating and amplifying signals from all major adhesion, activation, and inhibitory receptors, including the integrin αIIbß3, the collagen receptor complex glycoprotein VI-Fc receptor γ-chain, the G protein-coupled ADP receptor P2Y12 and the inhibitory receptors platelet endothelial cell adhesion molecule-1 and G6b-B. The vital roles of SFKs in platelets is highlighted by the severe phenotypes of null and gain-of-function mutations in SFKs in mice and humans, and effects of pharmacologic inhibitors on platelet activation, thrombosis, and hemostasis. The recent description of critical regulators of SFKs in platelets, namely, C-terminal Src kinase (Csk), Csk homologous kinase (Chk), the receptor-type protein-tyrosine phosphatase receptor type J (PTPRJ) helps explain some of the bleeding side effects of tyrosine kinase inhibitors and are novel therapeutic targets for regulating the thrombotic and hemostatic capacity of platelets. Recent findings from Chk, Csk, and PTPRJ knockout mouse models highlighted that SFKs are able to autoinhibit by phosphorylating their C-terminal tyrosine residues, providing fundamental insights into SFK autoregulation.

When Guidelines Fail: Euglycemic Diabetic Ketoacidosis After Bariatric Surgery in a Patient Taking a Sodium-Glucose Cotransporter-2 Inhibitor: A Case Report.

A 42-year-old woman with diabetes mellitus type 2 treated with the sodium-glucose cotransporter-2 inhibitor canagliflozin underwent elective bariatric gastric bypass. The canagliflozin was held for 24 hours preoperatively. She physiologically decompensated on postoperative day 2. Ultimately, she was diagnosed with euglycemic diabetic ketoacidosis that required intensive care management. This diagnosis was challenging to make as the patient never became hyperglycemic. We use this case to discuss the pharmacology and potential risk of perioperative sodium glucose cotransporter-2 inhibitor administration and to advocate for revision of current guidelines regarding the perioperative management of these agents.

Radiotherapy for intubated patients with malignant airway obstruction: futile or facilitating extubation?

INTRODUCTION: The optimal approach to patients with malignant airway obstruction who require intubation and mechanical ventilation but are ineligible for bronchoscopic interventions is uncertain. Radiotherapy (RT) may be delivered but requires substantial resources in this patient population. In the absence of evidence, it is unknown whether RT facilitates extubation or delays an appropriate transition to end-of-life care. METHODS: We performed a 10-year retrospective review of intensive care unit (ICU) patients treated with RT while on mechanical ventilation for malignant airway obstruction. Primary study endpoints were overall survival (OS) and extubation success (ES), defined as 48 hours or more without reintubation or death. Secondary endpoints included rates of discharge from the ICU and to home. Logistic regression and Cox regression analyses were performed to identify factors associated with OS and ES. RESULTS: Twenty-six patients were eligible for analysis. Seven patients (27%) were extubated; extubations occurred between days 4 and 22 after RT initiation. All patients were discharged from the ICU and most (n = 6) were also discharged home. An association between higher radiation doses and ES was observed (odds ratio per 5 Gy increase: 0.63; p = 0.080). Median OS was only 0.36 months (range, 0-113 months), and 6-month OS was 11%. On Cox regression analysis, increased radiation dose was predictive of improved OS (hazard ratio per 5 Gy increase: 0.74; p = 0.016). CONCLUSIONS: A significant minority of patients receiving RT were successfully extubated. Higher radiation doses were predictive of improved OS and showed a trend for increased ES. Survival beyond 6 months was uncommon, however, the majority of patients with ES were able to be discharged home.