Impact of preoperative depression on 2-year clinical outcomes following adult spinal deformity surgery: the importance of risk stratification based on type of psychological distress.

OBJECTIVE The objective of this study was to isolate whether the effect of a baseline clinical history of depression on outcome is independent of associated physical disability and to evaluate which mental health screening tool has the most utility in determining 2-year clinical outcomes after adult spinal deformity (ASD) surgery. METHODS Consecutively enrolled patients with ASD in a prospective, multicenter ASD database who underwent surgical intervention with a minimum 2-year follow-up were retrospectively reviewed. A subset of patients who completed the Distress and Risk Assessment Method (DRAM) was also analyzed.

[(124)I]FIAU: Human dosimetry and infection imaging in patients with suspected prosthetic joint infection.

Introduction: Fialuridine (FIAU) is a nucleoside analog that is a substrate for bacterial thymidine kinase (TK). Once phosphorylated by TK, [(124)I]FIAU becomes trapped within bacteria and can be detected with positron emission tomography/computed tomography (PET/CT). [(124)I]FIAU PET/CT has been shown to detect bacteria in patients with musculoskeletal bacterial infections.

Use of heparins in patients with cancer: individual participant data meta-analysis of randomised trials study protocol.

Introduction: Parenteral anticoagulants may improve outcomes in patients with cancer by reducing risk of venous thromboembolic disease and through a direct antitumour effect. Study-level systematic reviews indicate a reduction in venous thromboembolism and provide moderate confidence that a small survival benefit exists. It remains unclear if any patient subgroups experience potential benefits.

Extending resuscitative endovascular balloon occlusion of the aorta: Endovascular variable aortic control in a lethal model of hemorrhagic shock.

Background: The duration of use and efficacy of resuscitative endovascular balloon occlusion of the aorta (REBOA) is limited by distal ischemia. We developed a hybrid endovascular-extracorporeal circuit variable aortic control (VAC) device to extend REBOA duration in a lethal model of hemorrhagic shock to serve as an experimental surrogate to further the development of endovascular VAC (EVAC) technologies.

Methods: Nine Yorkshire-cross swine were anesthetized, instrumented, splenectomized, and subjected to 30% liver amputation.

Are frailty markers associated with serious thoracic and spinal injuries among motor vehicle crash occupants?

Background: While age is a known risk factor in trauma, markers of frailty are growing in their use in the critically ill. Frailty markers may reflect underlying strength and function more than chronologic age, as many modern elderly patients are quite active. However, the optimal markers of frailty are unknown.

All-Trans-Retinoic Acid Enhances Mitochondrial Function in Models of Human Liver.

All-trans-retinoic acid (atRA) is the active metabolite of vitamin A. The liver is the main storage organ of vitamin A, but activation of the retinoic acid receptors (RARs) in mouse liver and in human liver cell lines has also been shown. AlthoughatRA treatment improves mitochondrial function in skeletal muscle in rodents, its role in modulating mitochondrial function in the liver is controversial, and little data are available regarding the human liver.

The Effects of Nitrate-Rich Supplementation on Neuromuscular Efficiency during Heavy Resistance Exercise.

Objective: Nitrate-rich (NR) supplements can enhance exercise performance by improving neuromuscular function and the aerobic cost of exercise. However, little is known about the effects of nitrate on dynamic, multijoint resistance exercise.

Methods: Fourteen resistance-trained men (age, 21.

Structural Analysis on the Pathologic Mutant Glucocorticoid Receptor Ligand-Binding Domains.

Glucocorticoid receptor (GR) gene mutations may cause familial or sporadic generalized glucocorticoid resistance syndrome. Most of the missense forms distribute in the ligand-binding domain and impair its ligand-binding activity and formation of the activation function (AF)-2 that binds LXXLL motif-containing coactivators. We performed molecular dynamics simulations to ligand-binding domain of pathologic GR mutants to reveal their structural defects.

Chronic Glucose Exposure Systematically Shifts the Oscillatory Threshold of Mouse Islets: Experimental Evidence for an Early Intrinsic Mechanism of Compensation for Hyperglycemia.

Mouse islets exhibit glucose-dependent oscillations in electrical activity, intracellular Ca(2+) and insulin secretion. We developed a mathematical model in which a left shift in glucose threshold helps compensate for insulin resistance. To test this experimentally, we exposed isolated mouse islets to varying glucose concentrations overnight and monitored their glucose sensitivity the next day by measuring intracellular Ca(2+), electrical activity, and insulin secretion.

CRTC2 Is a Coactivator of GR and Couples GR and CREB in the Regulation of Hepatic Gluconeogenesis.

Glucocorticoid hormones play essential roles in the regulation of gluconeogenesis in the liver, an adaptive response that is required for the maintenance of circulating glucose levels during fasting. Glucocorticoids do this by cooperating with glucagon, which is secreted from pancreatic islets to activate the cAMP-signaling pathway in hepatocytes. The cAMP-response element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) is a coactivator known to be specific to CREB and plays a central role in the glucagon-mediated activation of gluconeogenesis in the early phase of fasting.

GABA and Glutamate in Children with Primary Complex Motor Stereotypies: An 1H-MRS Study at 7T.

Background And Purpose: Complex motor stereotypies are rhythmic, repetitive, fixed, purposeful but purposeless movements that stop with distraction. They can occur in otherwise normal healthy children (primary stereotypies) as well in those with autism spectrum disorders (secondary stereotypies). The underlying neurobiologic basis for these movements is unknown but is thought to involve cortical-striatal-thalamo-cortical pathways.

(1→3)-β-d-Glucan and Galactomannan for Differentiating Chemical "Black Particles" and Fungal Particles Inside Peritoneal Dialysis Tubing.

Unlabelled: ♦

Background: Aseptic, sheet-like foreign bodies observed inside Tenckhoff (TK) catheter lumens (referred to as "black particles") are, on gross morphology, hardly distinguishable from fungal colonization because these contaminants adhere tightly to the catheter. Detection of fungal cell wall components using (1→3)-β-d-glucan (BG) and galactomannan index (GMI) might be an alternative method for differentiating the particles. ♦

Methods: Foreign particles retrieved from TK catheters in 19 peritoneal dialysis patients were examined microscopically and cultured for fungi and bacteria.

Trauma-induced heterotopic bone formation and the role of the immune system: A review.

Extremity trauma, spinal cord injuries, head injuries, and burn injuries place patients at high risk of pathologic extraskeletal bone formation. This heterotopic bone causes severe pain, deformities, and joint contractures. The immune system has been increasingly implicated in this debilitating condition.

Depression and human immunodeficiency virus infection are risk factors for incident heart failure among veterans: Veterans Aging Cohort Study.

Background: Both HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among adults with HIV infection (HIV+). We assessed the association between HIV, depression, and incident HF.

Compound A Inhibits Bladder Cancer Growth Predominantly via Glucocorticoid Receptor Transrepression.

Recent evidence indicates that glucocorticoids (GCs) suppress bladder cancer cell invasion through the GC receptor (GR) pathway, whereas androgen-mediated androgen receptor (AR) signals induce bladder tumor progression. In this study, we assessed the effects of 2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride (compound A [CpdA]), which was shown to function as not only a GR modulator but also an AR antagonist, on the growth of bladder cancer. In GR/AR-positive cells, CpdA strongly inhibited cell proliferation and colony formation as well as increased G1 phase-arrested cell population and apoptosis.

AVI-7288 for Marburg Virus in Nonhuman Primates and Humans.

Background: AVI-7288 is a phosphorodiamidate morpholino oligomer with positive charges that targets the viral messenger RNA that encodes Marburg virus (MARV) nucleoprotein. Its safety in humans is undetermined.

Methods: We assessed the efficacy of AVI-7288 in a series of studies involving a lethal challenge with MARV in nonhuman primates.

Temporal Changes in Periprocedural Events in the Carotid Revascularization Endarterectomy Versus Stenting Trial.

Background And Purpose: Post-hoc, we hypothesized that over the recruitment period of the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST), increasing experience and improved patient selection with carotid stenting, and to a lesser extent, carotid endarterectomy would contribute to lower periprocedural event rates.

Methods: Three study periods with approximately the same number of patients were defined to span recruitment. Composite and individual rates of periprocedural stroke, myocardial infarction, and death rate were calculated separately by treatment assignment (carotid stenting/carotid endarterectomy).

Blood far forward: Time to get moving!

In planning for future contingencies, current problems often crowd out historical perspective and planners often turn to technological solutions to bridge gaps between desired outcomes and the reality of recent experience. The US Military, North Atlantic Treaty Organization, and other allies are collectively taking stock of 10-plus years of medical discovery and rediscovery of combat casualty care after the wars in Iraq and Afghanistan. There has been undeniable progress in the treatment of combat wounded during the course of the conflicts in Southwest Asia, but continued efforts are required to improve hemorrhage control and provide effective prehospital resuscitation that treats both coagulopathy and shock.

Design of a functional cyclic HSV1-TK reporter and its application to PET imaging of apoptosis.

Positron emission tomography (PET) is a sensitive and noninvasive imaging method that is widely used to explore molecular events in living subjects. PET can precisely and quantitatively evaluate cellular apoptosis, which has a crucial role in various physiological and pathological processes. In this protocol, we describe the design and use of an engineered cyclic herpes simplex virus 1-thymidine kinase (HSV1-TK) PET reporter whose kinase activity is specifically switched on by apoptosis.

Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitis.

Context: Central diabetes insipidus (CDI) can be caused by several diseases, but in about half of the patients the etiological diagnosis remains unknown. Lymphocytic infundibulo-neurohypophysitis (LINH) is an increasingly recognized entity among cases of idiopathic CDI; however, the differential diagnosis from other pituitary diseases including tumors can be difficult because of similar clinical and radiological manifestations. The definite diagnosis of LINH requires invasive pituitary biopsy.

Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis.

Objective: The objective was to determine the risk of stroke associated with subclinical hypothyroidism.

Data Sources And Study Selection: Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration.

Effects of red-cell storage duration on patients undergoing cardiac surgery.

Background: Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion.

Methods: We conducted a randomized trial at multiple sites from 2010 to 2014.

c-MYC Generates Repair Errors via Increased Transcription of Alternative-NHEJ Factors, LIG3 and PARP1, in Tyrosine Kinase-Activated Leukemias.

Unlabelled: Leukemias expressing the constitutively activated tyrosine kinases (TK) BCR-ABL1 and FLT3/ITD activate signaling pathways that increase genomic instability through generation of reactive oxygen species (ROS), DNA double-strand breaks (DSB), and error-prone repair. The nonhomologous end-joining (NHEJ) pathway is a major pathway for DSB repair and is highly aberrant in TK-activated leukemias; an alternative form of NHEJ (ALT-NHEJ) predominates, evidenced by increased expression of DNA ligase IIIα (LIG3) and PARP1, increased frequency of large genomic deletions, and repair using DNA sequence microhomologies. This study, for the first time, demonstrates that the TK target c-MYC plays a role in transcriptional activation and subsequent expression of LIG3 and PARP1 and contributes to the increased error-prone repair observed in TK-activated leukemias.