Multimodal imaging of metabolic activities for distinguishing subtypes of breast cancer.

Triple negative breast cancer (TNBC) is a highly aggressive form of cancer. Detecting TNBC early is crucial for improving disease prognosis and optimizing treatment. Unfortunately, conventional imaging techniques fall short in providing a comprehensive differentiation of TNBC subtypes due to their limited sensitivity and inability to capture subcellular details.

Reversible Cl/Cl redox in a spinel MnO electrode.

A unique prospect of using halides as charge carriers is the possibility of the halides undergoing anodic redox behaviors when serving as charge carriers for the charge-neutrality compensation of electrodes. However, the anodic conversion of halides to neutral halogen species has often been irreversible at room temperature due to the emergence of diatomic halogen gaseous products. Here, we report that chloride ions can be reversibly converted to near-neutral atomic chlorine species in the MnO electrode at room temperature in a highly concentrated chloride-based aqueous electrolyte.

Measuring the Enthalpy of an Individual Hydrogen Bond in a DNA Duplex with Nucleobase Isotope Editing and Variable-Temperature Infrared Spectroscopy.

The level of interest in probing the strength of noncovalent interactions in DNA duplexes is high, as these weak forces dictate the range of suprastructures the double helix adopts under different conditions, in turn directly impacting the biological functions and industrial applications of duplexes that require making and breaking them to access the genetic code. However, few experimental tools can measure these weak forces embedded within large biological suprastructures in the native solution environment. Here, we develop experimental methods for detecting the presence of a single noncovalent interaction [a hydrogen bond (H-bond)] within a large DNA duplex in solution and measure its formation enthalpy (Δ).

Histone lysine demethylase KDM4B regulates the alternative splicing of the androgen receptor in response to androgen deprivation.

Alternative splicing is emerging as an oncogenic mechanism. In prostate cancer, generation of constitutively active forms of androgen receptor (AR) variants including AR-V7 plays an important role in progression of castration-resistant prostate cancer (CRPC). AR-V7 is generated by alternative splicing that results in inclusion of cryptic exon CE3 and translation of truncated AR protein that lacks the ligand binding domain.

Enzalutamide-Induced Feed-Forward Signaling Loop Promotes Therapy-Resistant Prostate Cancer Growth Providing an Exploitable Molecular Target for Jak2 Inhibitors.

The second-generation antiandrogen, enzalutamide, is approved for castrate-resistant prostate cancer (CRPC) and targets androgen receptor (AR) activity in CRPC. Despite initial clinical activity, acquired resistance to enzalutamide arises rapidly and most patients develop terminal disease. Previous work has established Stat5 as a potent inducer of prostate cancer growth.

STAT5A/B Blockade Sensitizes Prostate Cancer to Radiation through Inhibition of RAD51 and DNA Repair.

The standard treatment for organ-confined prostate cancer is surgery or radiation, and locally advanced prostate cancer is typically treated with radiotherapy alone or in combination with androgen deprivation therapy. Here, we investigated whether Stat5a/b participates in regulation of double-strand DNA break repair in prostate cancer, and whether Stat5 inhibition may provide a novel strategy to sensitize prostate cancer to radiotherapy. Stat5a/b regulation of DNA repair in prostate cancer was evaluated by comet and clonogenic survival assays, followed by assays specific to homologous recombination (HR) DNA repair and nonhomologous end joining (NHEJ) DNA repair.

Androgen receptor-dependent and -independent mechanisms driving prostate cancer progression: Opportunities for therapeutic targeting from multiple angles.

Despite aggressive treatment for localized cancer, prostate cancer (PC) remains a leading cause of cancer-related death for American men due to a subset of patients progressing to lethal and incurable metastatic castrate-resistant prostate cancer (CRPC). Organ-confined PC is treated by surgery or radiation with or without androgen deprivation therapy (ADT), while options for locally advanced and disseminated PC include radiation combined with ADT, or systemic treatments including chemotherapy. Progression to CRPC results from failure of ADT, which targets the androgen receptor (AR) signaling axis and inhibits AR-driven proliferation and survival pathways.

Overtreatment of Heparin-Induced Thrombocytopenia in the Surgical ICU.

Objective: Recent studies reveal a high occurrence of overdiagnosis of heparin-induced thrombocytopenia in surgical patients with critical illness. The optimal criteria for diagnosis of heparin-induced thrombocytopenia remain unclear, contributing to unnecessary treatment. We reviewed patients who were admitted to surgical ICUs and were suspected of heparin-induced thrombocytopenia to identify how often patients were correctly treated.

High-value care in the surgical intensive care unit: effect on ancillary resources.

Background: Changes in health care policies have influenced transformations in hospital systems to be cost-efficient while maintaining robust outcomes. This is particularly important in intensive care units where significant resources are used to care for critically ill patients. We sought to determine whether high-value care processes (HVCp) implemented in a surgical intensive care unit (SICU) have an impact on commonly used ancillary tests.

Body mass index strongly impacts the diagnosis and incidence of heparin-induced thrombocytopenia in the surgical intensive care unit.

Background: The obese state has been linked to several immune-mediated conditions. Our objective was to examine the association of body mass index (BMI) with the diagnosis of heparin-induced thrombocytopenia (HIT).

Methods: Prospectively collected data on patients in the surgical and cardiac intensive care unit suspected of having HIT between January 2007 and August 2014 were analyzed.

CT Chest with IV Contrast Compared with CT Angiography after Blunt Trauma.

Blunt aortic injury (BAI) after chest trauma is a potentially lethal condition. Rapid diagnosis is important to appropriately treat patients. The purpose of this study was to compare CT with intravenous contrast (CTI) to CT with angiography (CTA) in the initial evaluation of blunt chest trauma patients.

CT Chest with IV Contrast Compared with CT Angiography after Blunt Trauma.

Blunt aortic injury (BAI) after chest trauma is a potentially lethal condition that requires rapid diagnosis for appropriate treatment. We compared CT with IV contrast (CTI) with CT with angiography (CTA) during the initial phase of care at an urban Level I trauma center from January 1, 2010 to December 31, 2013. Overall, 281 patients met inclusion criteria with 167 (59%) CTI and 114 (41%) CTA.

Selective Nonoperative Management of Abdominal Stab Wounds.

Stab wounds (SW) to the abdomen traditionally require urgent exploration when associated with shock, evisceration, or peritonitis. Hemodynamically stable patients without evisceration may benefit from serial exams even with peritonitis. We compared patients taken directly to the operating room with abdominal SWs (ED-OR) to those admitted for serial exams (ADMIT).

Epidural Analgesia after Rib Fractures.

Pain associated with rib fractures impairs respiratory function and increases pulmonary morbidity. The purpose of this study was to determine how epidural catheters alter mortality and complications in trauma patients. We performed a retrospective study involving adult blunt trauma patients with moderate-to-severe injuries from January 1, 2004 to December 31, 2013.

Activation of Massive Transfusion for Elderly Trauma Patients.

Massive transfusion protocol (MTP) is used to resuscitate patients in hemorrhagic shock. Our goal was to review MTP use in the elderly. All trauma patients who required activation of MTP at an urban Level I trauma center from January 1, 2011 to December 31, 2013 were reviewed retrospectively.

Jak2-Stat5a/b Signaling Induces Epithelial-to-Mesenchymal Transition and Stem-Like Cell Properties in Prostate Cancer.

Active Stat5a/b predicts early recurrence and disease-specific death in prostate cancer (PC), which both typically are caused by development of metastatic disease. Herein, we demonstrate that Stat5a/b induces epithelial-to-mesenchymal transition (EMT) of PC cells, as shown by Stat5a/b regulation of EMT marker expression (Twist1, E-cadherin, N-cadherin, vimentin, and fibronectin) in PC cell lines, xenograft tumors in vivo, and patient-derived PCs ex vivo using organ explant cultures. Jak2-Stat5a/b signaling induced functional end points of EMT as well, indicated by disruption of epithelial cell monolayers and increased migration and adhesion of PC cells to fibronectin.

Prospective evaluation of early propranolol after traumatic brain injury.

Background: Although beta-adrenergic receptor blockade may improve outcomes after traumatic brain injury (TBI), its early use is not routine. We hypothesize that judicious early low-dose propranolol after TBI (EPAT) will improve outcomes without altering bradycardia or hypotensive events.

Methods: We conducted a prospective, observational study on all patients who presented with moderate-to-severe TBI from March 2010-August 2013.

Structure-Based Screen Identifies a Potent Small Molecule Inhibitor of Stat5a/b with Therapeutic Potential for Prostate Cancer and Chronic Myeloid Leukemia.

Bypassing tyrosine kinases responsible for Stat5a/b phosphorylation would be advantageous for therapy development for Stat5a/b-regulated cancers. Here, we sought to identify small molecule inhibitors of Stat5a/b for lead optimization and therapy development for prostate cancer and Bcr-Abl-driven leukemias. In silico screening of chemical structure databases combined with medicinal chemistry was used for identification of a panel of small molecule inhibitors to block SH2 domain-mediated docking of Stat5a/b to the receptor-kinase complex and subsequent phosphorylation and dimerization.

Abdominal Injuries in the "Found Down": Is Imaging Indicated?

Background: We sought to investigate the incidence of abdominal injuries in "found down" trauma patients to better understand the value of emergency department (ED) imaging. Found down patients are at high risk for injuries to the head or neck and low risk to the abdomen or pelvis, so imaging with CT of the abdomen/pelvis (AP) or Focused Assessment with Sonography for Trauma (FAST) is of questionable value.

Study Design: The trauma registry was queried over a 10-year period ending December 2013 for found down patients.

Inhibition of Stat5a/b Enhances Proteasomal Degradation of Androgen Receptor Liganded by Antiandrogens in Prostate Cancer.

Although poorly understood, androgen receptor (AR) signaling is sustained despite treatment of prostate cancer with antiandrogens and potentially underlies development of incurable castrate-resistant prostate cancer. However, therapies targeting the AR signaling axis eventually fail when prostate cancer progresses to the castrate-resistant stage. Stat5a/b, a candidate therapeutic target protein in prostate cancer, synergizes with AR to reciprocally enhance the signaling of both proteins.

Pharmacologic suppression of JAK1/2 by JAK1/2 inhibitor AZD1480 potently inhibits IL-6-induced experimental prostate cancer metastases formation.

Metastatic prostate cancer is lethal and lacks effective strategies for prevention or treatment, requiring novel therapeutic approaches. Interleukin-6 (IL-6) is a cytokine that has been linked with prostate cancer pathogenesis by multiple studies. However, the direct functional roles of IL-6 in prostate cancer growth and progression have been unclear.

STAT5A/B gene locus undergoes amplification during human prostate cancer progression.

The molecular mechanisms underlying progression of prostate cancer (PCa) to castrate-resistant (CR) and metastatic disease are poorly understood. Our previous mechanistic work shows that inhibition of transcription factor Stat5 by multiple alternative methods induces extensive rapid apoptotic death of Stat5-positive PCa cells in vitro and inhibits PCa xenograft tumor growth in nude mice. Furthermore, STAT5A/B induces invasive behavior of PCa cells in vitro and in vivo, suggesting involvement of STAT5A/B in PCa progression.

Statewide ban on recreational fires resulted in a significant decrease in campfire-related summer burn center admissions.

Every summer, there is an increase in the number of burn injuries caused by accidents around campfires. Because of the prevalence of drought, high winds, and uncontrolled wild fires, a statewide ban on recreational fires was instituted in New Mexico from June to July 2011. We hypothesized that this legislation would have a significant impact on burn admissions caused by campfire-related injuries.

Prolactin regulation of the prostate gland: a female player in a male game.

Prolactin is best known for its actions on the mammary gland. However, circulating prolactin is also detected in males and its receptor (PRLR) is expressed in the prostate, suggesting that the prostate is a target of prolactin. Germline knockout of prolactin or its receptor has failed to reveal a key role for prolactin signaling in mouse prostate physiology.