Interplay between metabotropic glutamate type 4 and adenosine type 1 receptors modulate synaptic transmission in the cerebellar cortex.

The synapses between parallel fibers and Purkinje cells play a pivotal role in cerebellar function. They are intricately governed by a variety of presynaptic receptors, notably by type 4 metabotropic glutamate (mGlu4) receptors and type 1 adenosine (A1) receptors both of which curtail glutamate release upon activation. Despite their pivotal role in regulating synaptic transmission within the cerebellar cortex, functional interactions between mGlu4 and A1 receptors have remained relatively unexplored.

Design and Evaluation of an Interprofessional Preceptor Development Mini-Fellowship Program.

Introduction: Health professions preceptors require skills and knowledge to effectively meet the educational needs of interprofessional students in clinical environments. We implemented a mini-fellowship program to enhance the knowledge, skills, and self-efficacy of preceptors teaching students and applying quality improvement (QI) methods across disciplines and patient care settings.

Methods: The design, implementation, and evaluation of the program were informed by the faculty development literature, principles of adult learning, and preceptor needs.

Head Control Contributes to Prediction of Emergence From the Minimally Conscious State in Children Admitted to Inpatient Rehabilitation.

Objective: To examine the utility of head and trunk control, assessed using the Physical Abilities and Mobility Scale, for predicting emergence from a minimally conscious state (eMCS) among children with acquired brain injury admitted to inpatient rehabilitation in a disorder of consciousness (DoC).

Design: Retrospective study.

Setting: Pediatric inpatient rehabilitation hospital.

Differences in Safety Report Event Types Submitted by Graduate Medical Education Trainees Compared With Other Healthcare Team Members.

Objectives: Graduate medical education (GME) trainees have a unique perspective from which to identify and report patient safety concerns. However, it is not known how safety reports submitted by GME trainees differ from those submitted by other clinical staff. We hypothesized that GME trainees were more likely to submit safety reports regarding transitions of care, delays in care, and lapses in communication, and reports of higher severity compared with other frontline staff such as nurses, pharmacists, and other providers.

Initial Modified Pulmonary Index Score Predicts Hospital Length of Stay for Asthma Subjects Admitted to the Pediatric Intensive Care Unit.

Background: Scoring systems are frequently used to assess the severity of pediatric asthma exacerbations. The modified pulmonary index score (MPIS) has been found to be highly correlated with length of stay (LOS) in the pediatric intensive care unit (PICU). We sought to evaluate the use of the MPIS to predict hospital LOS for patients admitted to our PICU.

A Respiratory Therapist-Driven Asthma Pathway Reduced Hospital Length of Stay in the Pediatric Intensive Care Unit.

Background: Asthma is a common reason for admissions to the pediatric intensive care unit (PICU). Since June 2014, our institution has used a pediatric asthma clinical pathway for all patients, including those in PICU. The pathway promotes respiratory therapist-driven bronchodilator weaning based on the Modified Pulmonary Index Score (MPIS).

A Light-Controlled Allosteric Modulator Unveils a Role for mGlu Receptors During Early Stages of Ischemia in the Rodent Cerebellar Cortex.

Metabotropic glutamate receptors (mGlus) are G Protein coupled-receptors that modulate synaptic transmission and plasticity in the central nervous system. Some act as autoreceptors to control neurotransmitter release at excitatory synapses and have become attractive targets for drug therapy to treat certain neurological disorders. However, the high degree of sequence conservation around the glutamate binding site makes the development of subtype-specific orthosteric ligands difficult to achieve.

Increased Potency and Selectivity for Group III Metabotropic Glutamate Receptor Agonists Binding at Dual sites.

A group III metabotropic glutamate (mGlu) receptor agonist (PCEP) was identified by virtual HTS. This orthosteric ligand is composed by an l-AP4-derived fragment that mimics glutamate and a chain that binds into a neighboring pocket, offering possibilities to improve affinity and selectivity. Herein we describe a series of derivatives where the distal chain is replaced by an aromatic or heteroaromatic group.

Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation.

Antibodies have enormous therapeutic and biotechnology potential. G protein-coupled receptors (GPCRs), the main targets in drug development, are of major interest in antibody development programs. Metabotropic glutamate receptors are dimeric GPCRs that can control synaptic activity in a multitude of ways.

Native metabotropic glutamate receptor 4 depresses synaptic transmission through an unusual Gα transduction pathway.

In cerebellar cortex, mGlu receptors located on parallel fibers play an essential role in normal motor function, but the molecular mechanisms involved are not yet completely understood. Using a strategy combining biochemical and electrophysiological approaches in the rodent cerebellum, we demonstrate that presynaptic mGlu receptors control synaptic transmission through an atypical activation of Gα proteins. First, the Gα subunit, PLC and PKC signaling proteins present in cerebellar extracts are retained on affinity chromatography columns grafted with different sequences of the cytoplasmic domain of mGlu receptor.

Good to Great: Quality-Improvement Initiative Increases and Sustains Pediatric Health Care Worker Hand Hygiene Compliance.

Objective: The Joint Commission, the Centers for Disease Control and Prevention, and the World Health Organization challenge hospitals to achieve and sustain compliance with effective hand hygiene (HH) practice; however, many inpatient units fail to achieve a high level of reliability. The aim of the project was to increase and sustain health care worker (HCW) compliance with HH protocols from 87% (level of reliability [LOR] 1) to ≥95% (LOR 2) within 9 months on 2 pediatric inpatient units in an academic children's hospital.

Methods: This study was a time-series, quality-improvement project.

Improving the Efficiency of Care for Pediatric Patients Hospitalized With Asthma.

Background: Asthma exacerbations are a leading cause of hospitalization among children. Despite the existence of national pediatric asthma guidelines, significant variation in care persists. At Duke Children's Hospital, we determined that our average length of stay (ALOS) and cost for pediatric asthma admissions exceeded that of our peers.

The secure base script: associated with early maladaptive schemas related to attachment.

Objectives: To examine the relations between traditionally assessed early maladaptive schemas and the attachment-specific secure base script (a script-like representation of what individuals expect to happen when they face distress), to inform our understanding of beliefs about the self in relation to others. The present study took an ecologically driven approach, assessing knowledge of the secure base script from descriptions of current relationships.

Design: A cross-sectional design was used.

Choosing wisely in pediatric hospital medicine: five opportunities for improved healthcare value.

Background: Despite estimates that waste constitutes up to 20% of healthcare expenditures in the United States, overuse of tests and therapies is significantly under-recognized in medicine, particularly in pediatrics. The American Board of Internal Medicine Foundation developed the Choosing Wisely campaign, which challenged medical societies to develop a list of 5 things physicians and patients should question. The Society of Hospital Medicine (SHM) joined this effort in the spring of 2012.

Repeated split-belt treadmill training improves poststroke step length asymmetry.

Background And Objective: Previous studies suggest that error augmentation may be used as a strategy to achieve longer-term changes in gait deficits after stroke. The purpose of this study was to determine whether longer-term improvements in step length asymmetry could be achieved with repeated split-belt treadmill walking practice using an error augmentation strategy.

Methods: 13 persons with chronic stroke (>6 months) participated in testing: (1) prior to 12 sessions of split-belt treadmill training, (2) after the training, and (3) in follow-up testing at 1 and 3 months.

Use of ketamine during procedural sedation: indications, controversies, and side effects.

Ketamine is a well-described anesthetic and analgesic, unique in its ability to preserve laryngeal reflexes and airway protection, and offered to a wide range of patients, although not necessarily widely used. Because it is considered an anesthetic, widespread use by all sedation providers is often limited despite its long history as a safe sedative. Because of its sympathomimetic effects, ketamine may be used in patients who are hypovolemic, including those who are experiencing traumatic or obstetric emergencies.

A new signalling pathway for parallel fibre presynaptic type 4 metabotropic glutamate receptors (mGluR4) in the rat cerebellar cortex.

In the rodent cerebellum, pharmacological activation of mGluR4 acutely depresses excitatory synaptic transmission at parallel fibre–Purkinje cell synapses. This depression involves the inhibition of presynaptic calcium (Ca2+) influx that ultimately controls glutamate release. In this study, we investigate the molecular basis of mGluR4-mediated inhibition of presynaptic Ca2+ transients.

A novel selective metabotropic glutamate receptor 4 agonist reveals new possibilities for developing subtype selective ligands with therapeutic potential.

Metabotropic glutamate (mGlu) receptors are promising targets to treat numerous brain disorders. So far, allosteric modulators are the only subtype selective ligands, but pure agonists still have strong therapeutic potential. Here, we aimed at investigating the possibility of developing subtype-selective agonists by extending the glutamate-like structure to hit a nonconsensus binding area.

Role of the vesicular transporter VGLUT3 in retrograde release of glutamate by cerebellar Purkinje cells.

In the cerebellum, retrograde release of glutamate (Glu) by Purkinje cells (PCs) participates in the control of presynaptic neurotransmitter release responsible for the late component of depolarization-induced suppression of excitation (DSE), as well as for depolarization-induced potentiation of inhibition (DPI). It might also participate in the depolarization-induced slow current (DISC) in PCs, although this contribution was later challenged. We also know that both DPI and DISC are soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent processes, although the molecular nature of the vesicular transporter was not determined.

Split-belt treadmill training poststroke: a case study.

Background And Purpose: Even after rehabilitation, many individuals with strokes have residual gait deviations and limitations in functional walking. Applying the principles of motor adaptation through a split-belt treadmill walking paradigm can lead to short-term improvements in step length asymmetry after stroke. The focus of this case study was to determine whether it is possible to capitalize on these improvements for long-term gain.

The influence of the menstrual cycle on upper airway resistance and breathing during sleep.

Study Objective: Female hormones, specifically progesterone, that peak in the luteal phase may play a significant role in protecting premenopausal women from sleep-disordered breathing. The influence of female hormones on upper airway resistance during sleep was investigated during the follicular and luteal phases of normal menstrual cycles.

Setting: Hospital-based sleep laboratory.

Molecular cloning and functional characterization of a neuronal choline transporter from Trichoplusia ni.

A cDNA encoding a high-affinity Na(+)-dependent choline transporter (TrnCHT) was isolated from the CNS of the cabbage looper Trichoplusia ni using an RT-PCR-based approach. The deduced amino acid sequence of the CHT cDNA predicts a 594 amino acid protein of 64.74 kDa prior to glycosylation.

Daily time use as a measure of community adjustment for persons served by assertive community treatment teams.

Purpose: The purpose of the study was to examine daily time use of clients of Assertive Community Treatment (ACT) as a measure of their community adjustment and well-being. The actual daily time use of ACT clients in the four categories of personal care, productivity, leisure, and sleep were compared to the data for Canadian population norms.

Method: Daily time use data were collected from 27 adult clients from two Assertive Community Treatment Teams in southeastern Ontario using recall time diaries of two weekdays.

Functionally distinct dopamine and octopamine transporters in the CNS of the cabbage looper moth.

A cDNA was cloned from the cabbage looper Trichoplusia ni based on similarity to other cloned dopamine transporters (DATs). The total nucleotide sequence is 3.8 kb in length and contains an open reading frame for a protein of 612 amino acids.