Citations

ABSTRACTCervical spinal hemisection at C2 (SH) removes premotor drive to phrenic motoneurons located in segments C3–C5 in rats. Spontaneous recovery of ipsilateral diaphragm muscle activity is associated with increased phrenic motoneuron expression of glutamatergic N‐methyl‐D‐aspartate (NMDA) receptors and decreased expression of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐proprionic acid (AMPA) receptors. Glutamatergic receptor expression is regulated by tropomyosin‐related kinase receptor subtype B (TrkB) signaling in various neuronal systems, and increased TrkB receptor expression in phrenic motoneurons enhances recovery post‐SH. Accordingly, we hypothesize that recovery of ipsilateral diaphragm muscle activity post‐SH, whether spontaneous or enhanced by adenoassociated virus (AAV)‐mediated upregulation of TrkB receptor expression, is associated with increased expression of glutamatergic NMDA receptors in phrenic motoneurons. Adult male Sprague‐Dawley rats underwent diaphragm electromyography electrode implantation and SH surgery. Rats were injected intrapleurally with AAV expressing TrkB or GFP 3 weeks before SH. At 14 days post‐SH, the proportion of animals displaying recovery of ipsilateral diaphragm activity increased in AAV–TrkB‐treated (9/9) compared with untreated (3/5) or AAV–GFP‐treated (4/10; P < 0.027) animals. Phrenic motoneuron NMDA NR1 subunit mRNA expression was approximately fourfold greater in AAV–TrkB‐ vs. AAV–GFP‐treated SH animals (P < 0.004) and in animals displaying recovery vs. those not recovering (P < 0.005). Phrenic motoneuron AMPA glutamate receptor 2 (GluR2) subunit mRNA expression decreased after SH, and, albeit increased in animals displaying recovery vs. those not recovering, levels remained lower than control. We conclude that increased phrenic motoneuron expression of glutamatergic NMDA receptors is associated with spontaneous recovery after SH and enhanced recovery after AAV–TrkB treatment. J. Comp. Neurol. 525:1192–1205, 2017. © 2016 Wiley Periodicals, Inc.

Hematopoietic cell transplantation (HCT) is an important and complex treatment modality for a variety of hematologic malignancies and some solid tumors. Although outcomes of patients who have undergone HCT and require care in intensive care units (ICUs) have improved over time, mortality rates remain high and there are significant associated costs. Lack of a team-based approach to care, especially during critical illness, is detrimental to patient autonomy and satisfaction, and to team morale, ultimately leading to poor quality of care. In this manuscript, we describe the case of a patient who had undergone HCT and was in the ICU setting, where inconsistent team interaction among the various stakeholders delivering care resulted in a lack of shared goals and poor outcomes. Team cognition is cognitive processing at the team level through interactions among team members and is reflected in dynamic communication and coordination behaviors. Although the patient received multidisciplinary care as needed in a medically complicated case, a lack of team cognition and, particularly, inconsistent communication among the dynamic teams caring for the patient, led to mixed messages being delivered with high-cost implications for the health-care system and the family. This article highlights concepts and recommendations that begin a necessary in-depth assessment of implications for clinical care and initiate a research agenda that examines the effects of team cognition on HCT teams, and, more generally, critical care of the patient with cancer.

AbstractCulture conditions that induce hepatic spheroidal aggregates sustain liver cells with metabolism that mimics in vivo hepatocytes. Here we present an array of elastin‐like polypeptide conjugate coating materials (Aminated‐ELPs) that are biocompatible, have spheroid‐forming capacity, can be coated atop traditional culture surfaces, and maintain structural integrity while ensuring adherence of spheroids over long culture period. The Aminated‐ELPs were synthesized either by direct conjugation of ELP and various polyelectrolytes or by conjugating both ELP and various small electrolytes to the reactive polymer poly(2‐vinyl‐4,4‐dimethyl azlactone) (PVDMA). Spheroid morphology, cellular metabolic function, and liver‐specific gene expression over the long‐term, 20‐day culture period were assessed through optical microscopy, measurement of total protein content and albumin and urea production, and quantitative real‐time (qRT) PCR. We found that the amine content of the Aminated‐ELP coatings dictated the initial hepatocyte attachment, but not the subsequent hepatocyte spheroid formation and their continued attachment. A lower amine content was generally found to sustain higher albumin production by the spheroids. Out of the 19 Aminated‐ELP coatings tested, we found that the lysine‐containing substrates comprising ELP‐polylysine or ELP‐PVDMA‐butanediamine proved to consistently culture productive spheroidal hepatocytes. We suggest that the incorporation of lysine functional groups in Aminated‐ELP rendered more biocompatible surfaces, increasing spheroid attachment and leading to increased liver‐specific function. Taken together, the Aminated‐ELP array presented here has the potential to create in vitro hepatocyte culture models that mimic in vivo liver functionality and thus, lead to better understanding of liver pathophysiology and superior screening methods for drug efficacy and toxicity. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 377–388, 2017.

Abstract Dementia is often characterized as being caused by one of several major diseases, such as Alzheimer's disease (AD), cerebrovascular disease, Lewy body disease, or a frontotemporal degeneration. Failure to acknowledge that more than one entity may be present precludes attempts to understand interactive relationships. The clinicopathological studies of dementia demonstrate that multiple pathologic processes often coexist. How overlapping pathologic findings affect the diagnosis and treatment of clinical AD and other dementia phenotypes was the topic taken up by the Alzheimer's Association's Research Roundtable in October 2014. This review will cover the neuropathologic basis of dementia, provide clinical perspectives on multiple pathologies, and discuss therapeutics and biomarkers targeting overlapping pathologies and how these issues impact clinical trials.High prevalence of multiple pathologic findings among individuals with clinical diagnosis of AD suggests that new treatment strategies may be needed to effectively treat AD and other dementing illnesses.

An 81-year-old woman with well-controlled hypertension presented to the emergency department with new-onset atrial fibrillation with rapid ventricular response. Treatment for atrial fibrillation was initiated, including rate control and anticoagulation with 5 mg of apixaban two times per day for primary stroke prophylaxis. Three days after initiation of apixaban, the patient noted new-onset abdominal pain, worsening shortness of breath and weakness. Laboratory results showed elevated liver enzymes. Workup for elevated transaminase did not reveal any underlying infectious or autoimmune process. Apixaban, a probable cause for the hepatocellular injury, was discontinued and replaced with intravenous unfractionated heparin to bridge anticoagulation with warfarin. The patient's symptoms resolved as her transaminases improved by discontinuation of apixaban. We illustrate this case of drug-induced hepatotoxicity secondary to treatment with apixaban. It is important for physicians to be aware of this rare adverse effect caused by a widely used novel oral anticoagulant.

AbstractBackgroundInfantile colic is a frequent problem in neonates and infants. This review addresses current management including the results for nutrient modifications; soy‐based formulas; and prebiotics, probiotics, and synbiotics.PurposeGiven the evidence that there is still an unmet clinical need, as current treatments are incompletely efficacious, we have examined the evidence around three hypothetical mechanisms that could potentially be involved in etiopathogenesis of infantile colic: immaturity of bile acid mechanisms that alter intraluminal and absorptive mechanisms, immaturity in motility and alterations in the microbiome. Understanding these potential mechanisms may lead to the introduction of diagnostic procedures that should enhance the selection or individualization of therapy for infantile colic.