CRYAB plays a role in terminating the presence of pro-inflammatory macrophages in the older, injured mouse peripheral nervous system.

Evidence indicates that dysfunction of older Schwann cells and macrophages contributes to poor regeneration of more mature peripheral nervous system (PNS) neurons after damage. Since the underlying molecular factors are largely unknown, we investigated if CRYAB, a small heat shock protein that is expressed by Schwann cells and axons and whose expression declines with age, impacts prominent deficits in the injured, older PNS including down-regulation of cholesterol biosynthesis enzyme genes, Schwann cell dysfunction, and macrophage persistence. Following sciatic nerve transection injury in 3- and 12-month-old wildtype and CRYAB knockout mice, we found by bulk RNA sequencing and RT-PCR, that while gene expression of cholesterol biosynthesis enzymes is markedly dysregulated in the aging, injured PNS, CRYAB is not involved.

A failure in the medication delivery system-how disclosure and systems investigation improve patient safety.

A recent medication error at Vanderbilt University Medical Center contributed to the death of a patient. The ensuing criminal indictment of the administering nurse has shaken the medical community. This has led to clinical staff questioning whether they can disclose patient safety incidents without fear of criminal prosecution.

A novel metabolism-based phenotypic drug discovery platform in zebrafish uncovers HDACs 1 and 3 as a potential combined anti-seizure drug target.

Despite the development of newer anti-seizure medications over the past 50 years, 30-40% of patients with epilepsy remain refractory to treatment. One explanation for this lack of progress is that the current screening process is largely biased towards transmembrane channels and receptors, and ignores intracellular proteins and enzymes that might serve as efficacious molecular targets. Here, we report the development of a novel drug screening platform that harnesses the power of zebrafish genetics and combines it with in vivo bioenergetics screening assays to uncover therapeutic agents that improve mitochondrial health in diseased animals.

Metabotropic NMDA receptor signaling couples Src family kinases to pannexin-1 during excitotoxicity.

Overactivation of neuronal N-methyl-D-aspartate receptors (NMDARs) causes excitotoxicity and is necessary for neuronal death. In the classical view, these ligand-gated Ca(2+)-permeable ionotropic receptors require co-agonists and membrane depolarization for activation. We report that NMDARs signal during ligand binding without activation of their ion conduction pore.

Axo-glial communication through neurexin-neuroligin signaling regulates myelination and oligodendrocyte differentiation.

Axonal transsynaptic signaling between presynaptic neurexin (NX) and postsynaptic neuroligin (NL) is essential for many properties of synaptic connectivity. Here, we demonstrate the existence of a parallel axo-glial signaling pathway between axonal NX and oligodendritic (OL) NL3. We show that this pathway contributes to the regulation of myelinogenesis, the maintenance of established myelination, and the differentiation state of the OL using in vitro models.

Inorganic polyphosphate regulates neuronal excitability through modulation of voltage-gated channels.

Background: Inorganic polyphosphate (polyP) is a highly charged polyanion capable of interacting with a number of molecular targets. This signaling molecule is released into the extracellular matrix by central astrocytes and by peripheral platelets during inflammation. While the release of polyP is associated with both induction of blood coagulation and astrocyte extracellular signaling, the role of secreted polyP in regulation of neuronal activity remains undefined.

Surgical checklists: a systematic review of impacts and implementation.

Background: Surgical complications represent a significant cause of morbidity and mortality with the rate of major complications after inpatient surgery estimated at 3-17% in industrialised countries. The purpose of this review was to summarise experience with surgical checklist use and efficacy for improving patient safety.

Methods: A search of four databases (MEDLINE, CINAHL, EMBASE and the Cochrane Database of Controlled Trials) was conducted from 1 January 2000 to 26 October 2012.

High dose folic acid supplementation of rats alters synaptic transmission and seizure susceptibility in offspring.

Maternal folic acid supplementation is essential to reduce the risk of neural tube defects. We hypothesize that high levels of folic acid throughout gestation may produce neural networks more susceptible to seizure in offspring. We hence administered large doses of folic acid to rats before and during gestation and found their offspring had a 42% decrease in their seizure threshold.

Assessment of the TASER XREP blunt impact and penetration injury potential using cadaveric testing.

TASER International's extended range electronic projectile (XREP) is intended to be fired from a shotgun, impact a threat, and apply remote neuromuscular incapacitation. This study investigated the corresponding potential of blunt impact injury and penetration. Forty-three XREP rounds were deployed onto two male human cadaver torsos at impact velocities between 70.

Cell line specific modulation of extracellular aβ42 by Hsp40.

Heat shock proteins (Hsps) are a set of molecular chaperones involved in cellular repair. They provide protective mechanisms that allow cells to survive potentially lethal insults, In response to a conditioning stress their expression is increased. Here we examined the connection between Hsps and Aβ(42), the amyloid peptide involved in the pathological sequence of Alzheimer's disease (AD).

Economic outcomes of percutaneous coronary intervention with drug-eluting stents versus bypass surgery for patients with left main or three-vessel coronary artery disease: one-year results from the SYNTAX trial.

Objectives: To evaluate the cost-effectiveness of alternative approaches to revascularization for patients with three-vessel or left main coronary artery disease (CAD).

Background: Previous studies have demonstrated that, despite higher initial costs, long-term costs with bypass surgery (CABG) in multivessel CAD are similar to those for percutaneous coronary intervention (PCI). The impact of drug-eluting stents (DES) on these results is unknown.

Viscoelastic and failure properties of spine ligament collagen fascicles.

The microstructural volume fractions, orientations, and interactions among components vary widely for different ligament types. If these variations are understood, however, it is conceivable to develop a general ligament model that is based on microstructural properties. This paper presents a part of a much larger effort needed to develop such a model.

Thoracic and lumbar spinal impact tolerance.

Introduction: Thoracolumbar injuries resulting from motor vehicle accidents, falls, and assaults have a high risk of morbidity and mortality. However, there are no biomechanically based standards that address this problem.

Methods: This study used four cadaveric porcine specimens as a model for direct spinal impact injuries to humans to determine an appropriate injury tolerance value.

Viscoelastic properties of the cervical spinal ligaments under fast strain-rate deformations.

The mechanical response of ligaments under fast strain-rate deformations is a necessary input into computational models that are used for injury assessment. However, this information frequently is not available for the ligaments that are routinely injured in fast-rate loading scenarios. In the current study, experiments were conducted at fast strain rates for the cervical spinal ligaments: the anterior longitudinal ligament, the posterior longitudinal ligament and the ligamentum flavum.

The temperature-dependent viscoelasticity of porcine lumbar spine ligaments.

Study Design: A uniaxial tensile loading study of 13 lumbar porcine ligaments under varying environmental temperature conditions.

Objectives: To investigate a possible temperature dependence of the material behavior of porcine lumbar anterior longitudinal ligaments.

Summary Of Background Data: Temperature dependence of the mechanical material properties of ligament has not been conclusively established.

Failure properties of cervical spinal ligaments under fast strain rate deformations.

Study Design: The failure responses of the anterior longitudinal ligament, posterior longitudinal ligament, and ligamentum flavum were examined in vitro under large strain-rate mechanical loading.

Objective: To quantify the failure properties for 3 cervical spinal ligaments at strain rates associated with traumatic events.

Summary Of Background Data: There exists little experimentation literature for fast-rate loading of the cervical spine ligaments.

Injury risk in behind armor blunt thoracic trauma.

First responders and military personnel are particularly susceptible to behind armor blunt thoracic trauma in occupational scenarios. The objective of this study was to develop an armored thorax injury risk criterion for short duration ballistic impacts. 9 cadavers and 2 anthropomorphic test dummies (AUSMAN and NIJ 0101.

Development of injury criteria for pelvic fracture in frontal crashes.

Objective: This article assesses the position-dependent injury tolerance of the hip in the frontal direction based on testing of eight postmortem human subjects.

Methods: For each subject, the left and right hemipelvis complex was axially loaded using a previously developed test configuration. Six positions were defined from a seated femur neutral condition, combining flexed, neutral, and extended femur positions with abducted, neutral, and adducted positions.

Group-beneficial traits, frequency-dependent selection and genotypic diversity: an antibiotic resistance paradigm.

The evolution of group-beneficial traits potentially allows the survival of 'cheaters' that would otherwise be unfit. Here we describe experimental work on group-beneficial traits and the consequences of frequency-dependent selection in the context of bacterial antibiotic resistance. We constructed a 'self-limited antibiotic resistant' (SLAR) strain of Escherichia coli in which a TEM-1 beta-lactamase was anchored to the inner membrane.