Myelination of parvalbumin interneurons: a parsimonious locus of pathophysiological convergence in schizophrenia

Schizophrenia is a debilitating psychiatric disorder characterized by positive, negative and cognitive symptoms. Despite more than a century of research, the neurobiological mechanism underlying schizophrenia remains elusive. White matter abnormalities and interneuron dysfunction are the most widely replicated cellular neuropathological alterations in patients with schizophrenia. However, a unifying model incorporating these findings has not yet been established. Here, we propose that myelination of fast-spiking parvalbumin (PV) interneurons could be an important locus of pathophysiological convergence in schizophrenia. Myelination of interneurons has been demonstrated across a wide diversity of brain regions and appears highly specific for the PV interneuron subclass. Given the critical influence of fast-spiking PV interneurons for mediating oscillations in the gamma frequency range (~30–120 Hz), PV myelination is well positioned to optimize action potential fidelity and metabolic homeostasis. We discuss this hypothesis with consideration of data from human postmortem studies, in vivo brain imaging and electrophysiology, and molecular genetics, as well as fundamental and translational studies in rodent models. Together, the parvalbumin interneuron myelination hypothesis provides a falsifiable model for guiding future studies of schizophrenia pathophysiology.Molecular Psychiatry advance online publication, 20 September 2016; doi:10.1038/mp.2016.147

Put Illinois To Work Evaluation: An Early Look

Though the recession is technically over, the large gap between available jobs and people in need of work necessitates a further discussion about the role subsidized employment programs play in supporting disadvantaged workers and struggling businesses through the recovery. While rigorously assessing the impact of Illinois' subsidized job program, Put Illinois to Work, on individuals, businesses, and communities will take many months, this early look can be an important contribution to pending federal and state discussions about whether and how to continue funding and running subsidized jobs programs as a response to the economic crisis.The Social IMPACT Research Center was commissioned to document and evaluate PITW's program model, outcomes, and impacts. This early report gives a brief overview of the program, explores an initial round of outcome data, and presents feedback from PITW workers and employers. Subsequent reports will present a fuller picture of outcomes, explore the details of and lessons learned from PITW's development and implementation, and assess in much greater detail the impact of the program on the lives of the workers and on the stability and viability of Illinois businesses

Changes in biomechanical properties of chemotherapy bone cement after a year in saline storage

Introduction: Acrylic based bone cements are a versatile treatment modality in Orthopaedic surgery due to their wide variety of uses and tolerance to high degree of customization. Bone cement can be used to repair and stabilize pathologic fractures and may potentially prevent recurrence post tumor resection. Chemotherapeutic bone cements are favorable because they can potentially minimize systemic side effects and the need for radiation. Cements can be combined with soluble fillers such as polyethylene glycol (PEG) to optimize drug elution. Even though studies have measured the mechanical properties of bone cement in dry state, the exact change in the mechanical properties of bone cement after drug/soluble filler elution is largely unknown. This study investigates the change in mechanical properties of commercially available bone cements modified with PEG fillers after one year of storage in drug elution medium. Methods: Confidence Ultra, Vertebroplastic, and Palacos cement were used and mixed with varying amounts (0–50%) of PEG and chemotherapy agents (methotrexate or doxorubicin). Bone cement specimens were stored in a saline solution for one year after which they were tested in compression at 1 mm/min until failure. Results: The modulus and compression strength of bone cements decreased with increase in soluble filler composition. Although soluble fillers were shown to weaken the mechanical properties of the bone cement, Palacos and Vertebroplastic cements retained their mechanical properties better than Confidence. Discussion: When using chemotherapeutic bone cements, combining soluble fillers enhances drug elution at the expense of mechanical properties. However, the results showed that mechanical properties of different commercially available bone cements behave differently with similar percentages of soluble filler and drug added making it difficult to predict changes in mechanical properties of bone cement intraoperatively. This elucidates the need for well characterized bone cement optimized for chemotherapy drug delivery

Comparison of Ventricular Refractory Periods Determined by Incremental and Decremental Scanning of an Extrastimulus

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73345/1/j.1540-8159.1989.tb02699.x.pd

Escherichia coli peptide methionine sulfoxide reductase gene:regulation of expression and role in protecting against oxidative damage

This is the publisher's version, also available electronically from "http://jb.asm.org".The Escherichia coli peptide methionine sulfoxide reductase gene (msrA) encodes a single-subunit polypeptide of 212 amino acid residues (M. A. Rahman, H. Nelson, H. Weissbach, and N. Brot, J. Biol. Chem. 267:15549-15551, 1992). RNA blot analysis showed that the gene is transcribed into an mRNA of about 850 nucleotides. The promoter region was characterized, and the transcription initiation site was identified by primer extension. The synthesis of the MsrA protein increased about threefold in a growth-phase-dependent fashion. In an attempt to define the in vivo role of msrA, a chromosomal disruption was constructed. This mutant was more sensitive to oxidative stress, suggesting that oxidation of methionine in proteins plays an important role in oxidative damage

In-House Digital Workflow for the Management of Acute Mandible Fractures

Computer-aided design and additive manufacturing are revolutionizing oral and maxillofacial surgery. Current methods use virtual surgical planning sessions and custom plate milling via third-party vendors, which is costly and time-consuming, negating the effectiveness in acute facial trauma. This technical note describes a state-of-the-art in-house expedited digital workflow for computer-aided virtual fracture reduction, 3-dimensional printing, and preoperative reconstruction plate adaptation for the management of an acute mandible fracture. This process uses the computed tomographic scan a patient receives in the emergency department or clinic. The DICOM (Digital Imaging and Communications in Medicine) data are transferred into US Food and Drug Administration–approved software, in which the fracture is segmented and virtually reduced based on condylar position, midline symmetries, and occlusion if present. The reduced mandible is then printed, which serves as a template for preoperative reconstruction plate adaptation. This method facilitates a virtually reduced fractured mandible, 3-dimensionally printed model, and ideally adapted plates ready for sterilization before surgery within 2 hours after DICOM upload

Fast-spiking Parvalbumin Interneurons are Frequently Myelinated in the Cerebral Cortex of Mice and Humans

Myelination, the insulating ensheathment of axons by oligodendrocytes, is thought to both optimize signal propagation and provide metabolic support. Despite the well-established physiological importance of myelination to neuronal function, relatively little is known about the myelination of GABAergic interneurons in the cerebral cortex. Here, we report that a large fraction of myelin in mouse cerebral cortex ensheaths GABAergic interneurons, reaching up to 80% in hippocampal subregions. Moreover, we find that a very high proportion of neocortical and hippocampal parvalbumin (PV) interneurons exhibit axonal myelination. Using a combination of intracellular recordings and biocytin labeling of ex vivo human neocortex, we also confirm that axons of fast-spiking PV interneurons are extensively myelinated in the human brain. PV interneuron myelination in both mice and humans exhibits a stereotyped topography with a bias towards proximal axonal segments and relatively short internodes (∼27 μm) interspersed with branch points. Interestingly, myelin-deficient Shiverer mice exhibit an increased density and more proximal location of en passant boutons, suggesting that myelination might function in part to regu

Synthetic Polymers Provide a Robust Substrate for Functional Neuron Culture

Substrates for neuron culture and implantation are required to be both biocompatible and display surface compositions that support cell attachment, growth, differentiation, and neural activity. Laminin, a naturally occurring extracellular matrix protein is the most widely used substrate for neuron culture and fulfills some of these requirements, however, it is expensive, unstable (compared to synthetic materials), and prone to batch-to-batch variation. This study uses a high-throughput polymer screening approach to identify synthetic polymers that supports the in vitro culture of primary mouse cerebellar neurons. This allows the identification of materials that enable primary cell attachment with high viability even under “serum-free” conditions, with materials that support both primary cells and neural progenitor cell attachment with high levels of neuronal biomarker expression, while promoting progenitor cell maturation to neurons.Biomaterials & Tissue Biomechanic

Effects of epinephrine in patients with an accessory atrioventricular connection treated with quinidine

The purpose of this study was to determine whether physiologic doses of epinephrine reverse the electrophysiologic effects of quinidine in patients with an accessory atrioventricular (AV) connection. Eighteen patients with an accessory AV connection who had inducible sustained orthodromic tachycardia underwent an electrophysiologic study in the baseline state and after at least 2 days of treatment with 1.4 to 1.9 g/day of quinidine gluconate. The effects of epinephrine were then determined. Epinephrine infusion rates of 25 and 50 ng/ kg/min were used in 9 patients each because these doses of epinephrine previously have been demonstrated to result in elevated plasma epinephrine concentrations in the range that occurs during a variety of stresses in humans. Quinidine prolonged refractoriness in the atrium and accessory AV connection and slowed conduction through the accessory AV connection. These effects were partially or completely reversed by epinephrine. Among 8 patients in whom quinidine resulted in orthodromic tachycardia becoming noninducible or nonsustained, sustained tachycardia became inducible again in 5 patients after infusion of epinephrine. After quinidine, atrial fibrillation was either non-inducible or nonsustained in 8 patients; however, sustained atrial fibrillation could be induced in 4 of these patients after infusion of epinephrine. The results of this study demonstrate that the therapeutic effect of quinidine in patients who have an accessory AV connection are often reversed by physiologic increases in circulating epinephrine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27138/1/0000131.pd

Integrating Data Variability Into Contemporary COVID-19 Decision Support

In April of 2020, the National Center for Disaster Preparedness (NCDP) at Columbia University’s Earth Institute partnered with Commonwealth Edison (ComEd) to examine the coronavirus disease 2019 (COVID-19) pandemic and support relevant decision-making to facilitate workforce safety and continuity of utility operations in an environment where initial data were scant and variable. Due to the gradual and variable emergence of information during disasters, precise data is a luxury in decision-making. Instead, we must rely on a dynamic approach, which integrates new information as it becomes available. Often, this requires a combined subjective and objective decision-making framework that shifts toward objectivity as data variability converges and becomes more precise