Adeno-associated viral tools to trace neural development and connectivity across amphibians.

Amphibians, by virtue of their phylogenetic position, provide invaluable insights on nervous system evolution, development, and remodeling. The genetic toolkit for amphibians, however, remains limited. Recombinant adeno-associated viral vectors (AAVs) are a powerful alternative to transgenesis for labeling and manipulating neurons.

Mutation of the Drosophila melanogaster serotonin transporter dSERT impacts sleep, courtship, and feeding behaviors.

The Serotonin Transporter (SERT) regulates extracellular serotonin levels and is the target of most current drugs used to treat depression. The mechanisms by which inhibition of SERT activity influences behavior are poorly understood. To address this question in the model organism Drosophila melanogaster, we developed new loss of function mutations in Drosophila SERT (dSERT).

Digital haptics improve speed of visual search performance in a dual-task setting.

Dashboard-mounted touchscreen tablets are now common in vehicles. Screen/phone use in cars likely shifts drivers' attention away from the road and contributes to risk of accidents. Nevertheless, vision is subject to multisensory influences from other senses.

Serotonergic modulation of visual neurons in Drosophila melanogaster.

Sensory systems rely on neuromodulators, such as serotonin, to provide flexibility for information processing as stimuli vary, such as light intensity throughout the day. Serotonergic neurons broadly innervate the optic ganglia of Drosophila melanogaster, a widely used model for studying vision. It remains unclear whether serotonin modulates the physiology of interneurons in the optic ganglia.

Notice to comply: A systematic review of clinician compliance with guidelines surrounding acute hospital-based infection management.

Purpose: To identify and characterize studies evaluating clinician compliance with infection-related guidelines, and to explore trends in guideline design and implementation strategies.

Data Sources: PubMed database, April 2017. Followed the PRISMA Statement for systematic reviews.

Data-driven approach to Early Warning Score-based alert management.

Background: Increasing adoption of electronic health records (EHRs) with integrated alerting systems is a key initiative for improving patient safety. Considering the variety of dynamically changing clinical information, it remains a challenge to design EHR-driven alerting systems that notify the right providers for the right patient at the right time while managing alert burden. The objective of this study is to proactively develop and evaluate a systematic alert-generating approach as part of the implementation of an Early Warning Score (EWS) at the study hospitals.

Multicenter observational study of the development of progressive organ dysfunction and therapeutic interventions in normotensive sepsis patients in the emergency department.

Objectives: Progressive organ dysfunction is the leading cause of sepsis-associated mortality; however, its incidence and management are incompletely understood. Sepsis patients with moderately impaired perfusion (serum lactate 2.0 to 3.

Discordance between microcirculatory alterations and arterial pressure in patients with hemodynamic instability.

Purpose: Recent studies reported that microcirculatory blood flow alterations occur in patients with circulatory shock independent of arterial pressure but typically lack baseline microcirculatory data before the insult and after recovery. We selected cardiopulmonary bypass (CPB) patients with expected and rapidly reversible hemodynamic instability to test the hypothesis that microcirculatory alterations can occur independent of mean arterial pressure (MAP).

Methods: Prospective observational study using sidestream darkfield videomicroscopy to measure sublingual microcirculatory flow preoperative (PRE), postoperatively after CPB (POST), and after recovery (REC).

Prognostic value and agreement of achieving lactate clearance or central venous oxygen saturation goals during early sepsis resuscitation.

Objectives: Lactate clearance (LC) and central venous oxygen saturation (ScvO(2)) have been proposed as goals of early sepsis resuscitation. The authors sought to determine the agreement and prognostic value of achieving ScvO(2) or LC goals in septic shock patients undergoing emergency department (ED)-based early resuscitation.

Methods: This was a preplanned analysis of a multicenter ED randomized controlled trial of early sepsis resuscitation targeting three variables: central venous pressure, mean arterial pressure, and either ScvO(2) or LC.

Association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol.

Objective: We sought to determine the association between time to initial antibiotics and mortality of patients with septic shock treated with an emergency department-based early resuscitation protocol.

Design: Preplanned analysis of a multicenter randomized controlled trial of early sepsis resuscitation.

Setting: Three urban U.

Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial.

Context: Goal-directed resuscitation for severe sepsis and septic shock has been reported to reduce mortality when applied in the emergency department.

Objective: To test the hypothesis of noninferiority between lactate clearance and central venous oxygen saturation (ScvO2) as goals of early sepsis resuscitation.

Design, Setting, And Patients: Multicenter randomized, noninferiority trial involving patients with severe sepsis and evidence of hypoperfusion or septic shock who were admitted to the emergency department from January 2007 to January 2009 at 1 of 3 participating US urban hospitals.

A prospective multicenter cohort study of the association between global tissue hypoxia and coagulation abnormalities during early sepsis resuscitation.

Objective: Coagulation activation is an integral part of sepsis pathogenesis. Experimental data suggest that endothelial exposure to hypoxia activates coagulation. We aimed to test the hypothesis that the quantity of exposure to global tissue hypoxia is associated with the degree of coagulation activation during early sepsis resuscitation.

Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis.

Study Objective: Abnormal (both low and high) central venous saturation (ScvO(2)) is associated with increased mortality in emergency department (ED) patients with suspected sepsis.

Methods: This was a secondary analysis of 4 prospectively collected registries of ED patients treated with early goal-directed therapy-based sepsis resuscitation protocols from 4 urban tertiary care hospitals. Inclusion criteria were sepsis, hypoperfusion defined by systolic blood pressure less than 90 mm Hg or lactate level greater than or equal to 4 mmol/L, and early goal-directed therapy treatment.

Point-of-care assessment of microvascular blood flow in critically ill patients.

Objective: Sublingual microvascular videomicroscopy can assess tissue perfusion in critically ill patients; however, data analysis is currently limited to delayed off-line evaluation. We hypothesized that a real-time point-of-care (POC) determination of the microcirculatory flow index (MFI), an established metric for assessing microcirculatory perfusion, agrees well with the conventional off-line analysis.

Design: Prospective observational study.

Multicenter study of early lactate clearance as a determinant of survival in patients with presumed sepsis.

We sought to determine (a) if early lactate clearance is associated with improved survival in emergency department patients with severe sepsis and (b) the concordance between central venous oxygen saturation (ScvO2) optimization and lactate clearance during early sepsis resuscitation. Within a multicenter shock research network that uses quantitative resuscitation for severe sepsis, we analyzed prospectively collected registries of consecutive emergency department patients diagnosed with severe sepsis at three urban hospitals. Inclusion criteria are as follows: (a) age older than 17 years, (b) two or more systemic inflammation criteria, (c) systolic blood pressure 90 mmHg or less after fluid challenge or initial lactate of 4 mmol/L or greater, and (d ) initial and repeat lactate measurement within 6 h of resuscitation initiation.

Continuous cardiac index monitoring: A prospective observational study of agreement between a pulmonary artery catheter and a calibrated minimally invasive technique.

Introduction: Continuous cardiac index (CCI) monitoring can provide information to assist in hemodynamic support. However, pulmonary artery catheters (PAC) pose logistic challenges in acute care settings. We hypothesized that CCI measured with a calibrated minimally invasive technique (LiDCO/PulseCO, UK) would have good agreement with the PAC.

The use of the OSCE in postgraduate education.

Background: The Objective Structured Clinical Examination (OSCE) is a method of assessing the clinical skills of undergraduates in medicine, dentistry and other health sciences and is employed increasingly in postgraduate education.

Aim: To describe the application of the OSCE to the development of Lifelong Learning and Continuing Professional Development (CPD) for General Dental Practitioners (GDPs).

Methods: A postgraduate course was designed as an OSCE for GDPs.

Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis.

Objective: Sepsis mortality is closely linked to multi-organ failure, and impaired microcirculatory blood flow is thought to be pivotal in the pathogenesis of sepsis-induced organ failure. We hypothesized that changes in microcirculatory flow during resuscitation are associated with changes in organ failure over the first 24 h of sepsis therapy.

Design: Prospective observational study.

Resuscitating the microcirculation in sepsis: the central role of nitric oxide, emerging concepts for novel therapies, and challenges for clinical trials.

Microcirculatory dysfunction is a critical element of the pathogenesis of severe sepsis and septic shock. In this Bench-to-Bedside review, we present: 1) the central role of the microcirculation in the pathophysiology of sepsis; 2) new translational research techniques of in vivo video microscopy for assessment of microcirculatory flow in human subjects; 3) clinical investigations that reported associations between microcirculatory dysfunction and outcome in septic patients; 4) the potential role of novel agents to "rescue" the microcirculation in sepsis; 5) current challenges facing this emerging field of clinical investigation; and 6) a framework for the design of future clinical trials aimed to determine the impact of novel agents on microcirculatory flow and organ failure in patients with sepsis. We specifically focus this review on the central role and vital importance of the nitric oxide (NO) molecule in maintaining microcirculatory homeostasis and patency, especially when the microcirculation sustains an insult (as with sepsis).

Serum lactate as a predictor of mortality in patients with infection.

Objective: To determine the utility of an initial serum lactate measurement for identifying high risk of death in patients with infection.

Design And Setting: Post-hoc analysis of a prospectively compiled registry in an urban academic hospital.

Participants: Patients with (a) a primary or secondary diagnosis of infection and (b) lactate measurement who were admitted over the 18 months following hospital-wide implementation of the Surviving Sepsis Campaign guideline for lactate measurement in patients with infection and possible severe sepsis.

Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival.

Study Objective: To study early microcirculatory perfusion indices in patients with severe sepsis/septic shock, compare early microcirculatory indices in sepsis survivors versus nonsurvivors, and identify systemic hemodynamic/oxygen transport variables that correlate with early microcirculatory perfusion indices.

Methods: This prospective observational study used orthogonal polarization spectral imaging to directly visualize the sublingual microcirculation in patients with severe sepsis/septic shock treated with early goal-directed therapy. We performed initial imaging within 6 hours of early goal-directed therapy initiation and late follow-up studies at 24-hour intervals until death or resolution of organ dysfunction.