Randomized Phase 2 Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease.

Background And Objectives: The goal of this work was to determine whether locally acting ACE-083 is safe and well tolerated and increases muscle volume, motor function, and quality of life (QoL) in adults with Charcot-Marie-Tooth disease (CMT) type 1.

Methods: This phase 2 study enrolled adults with CMT1 or CMTX (N = 63). Part 1 was open label and evaluated the safety and tolerability of different dose levels of ACE-083 for use in part 2.

Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy.

Introduction/aims: Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies. In this study we evaluated whether locally acting ACE-083 could safely increase muscle volume and improve functional outcomes in adults with FSHD.

Methods: Participants were at least 18 years old and had FSHD1/FSHD2.

Biomarker Analysis of Orally Dosed, Dual Active, Matrix Metalloproteinase (MMP)-2 and MMP-9 Inhibitor, AQU-118, in the Spinal Nerve Ligation (SNL) Rat Model of Neuropathic Pain.

There is an unmet medical need for the development of non-addicting pain therapeutics with enhanced efficacy and tolerability. The current study examined the effects of AQU-118, an orally active inhibitor of metalloproteinase-2 (MMP-2) and MMP-9, in the spinal nerve ligation (SNL) rat model of neuropathic pain. Mechanical allodynia and the levels of various biomarkers were examined within the dorsal root ganglion (DRG) before and after oral dosing with AQU-118.

Anti-hyperalgesic effects of AG490, a Janus kinase inhibitor, in a rat model of inflammatory pain.

Interleukin 6 (IL-6) has a critical role in pain mechanisms. IL-6 signals through the Janus-activated kinases 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) pathway. The contribution of JAK2 signaling in inflammation-induced hyperalgesia has not been addressed previously.

Prehospital and en route analgesic use in the combat setting: a prospectively designed, multicenter, observational study.

Background: Combat injuries result in acute, severe pain. Early use of analgesia after injury is known to be beneficial. Studies on prehospital analgesia in combat are limited and no prospectively designed study has reported the use of analgesics in the prehospital and en route care setting.

Prehospital pain medication use by U.S. Forces in Afghanistan.

We report the results of a process improvement initiative to examine the current use and safety of prehospital pain medications by U.S. Forces in Afghanistan.

State of the science review: Advances in pain management in wounded service members over a decade at war.

The pain conditions and comorbidities experienced by injured service members and the challenge of pain management by the military medical system offer a unique opportunity to inform pain management and medical research. In this article, acute and chronic pain issues, current treatment options and limitations, as well as novel approaches to pain management are discussed within the context of combat casualty care, from the battlefield to hospitalization and rehabilitation. This review will also highlight the current pain management limitations that need to be addressed in future clinical and basic science research to improve care for our nation's injured service members.

The intraoperative administration of ketamine to burned U.S. service members does not increase the incidence of post-traumatic stress disorder.

Aim: Patients with severe burns typically undergo multiple surgeries, and ketamine is often used as part of the multimodal anesthetic regimen during such surgeries. The anesthetic ketamine is an N-methyl-D-aspartate receptor antagonist that also provides analgesia at subanesthetic doses, but the psychoactive side effects of ketamine have caused concern about its potential psychological effects on a combat-wounded population. Post-traumatic stress disorder (PTSD) affects approximately 30% of burned U.

Activated 5'flanking region of NANOGP8 in a self-renewal environment is associated with increased sphere formation and tumor growth of prostate cancer cells.

Introduction: NANOGP8 is a retrogene which encodes a full-length protein similar to the NANOG1 gene. The expression of NANOGP8 has been documented in several cancers and is related to cell proliferation and tumor development. However, the regulation of NANOGP8 expression has not been investigated.

A rat model of full thickness thermal injury characterized by thermal hyperalgesia, mechanical allodynia, pronociceptive peptide release and tramadol analgesia.

Opioid-related side effects are problematic for burn patients. Dual mechanism therapeutics targeting opioid and non-opioid mechanisms may have reduced side effects with similar analgesic efficacy. Tramadol combines mu opioid receptor agonism with norepinephrine reuptake inhibition and has been effective in treating some types of pain.

Curcumin: a novel therapeutic for burn pain and wound healing.

Introduction: Managing burn injury-associated pain and wounds is a major unresolved clinical problem. Opioids, nonsteroidal antiinflammatory drugs (NSAIDs), antidepressants and anticonvulsants remain the most common forms of analgesic therapy to treat burn patients. However, prolonged treatment with these drugs leads to dose escalation and serious side effects.

Knockdown of core binding factorβ alters sphingolipid metabolism.

Core binding factor (CBF) is a heterodimeric transcription factor containing one of three DNA-binding proteins of the Runt-related transcription factor family (RUNX1-3) and the non-DNA-binding protein, CBFβ. RUNX1 and CBFβ are the most common targets of chromosomal rearrangements in leukemia. CBF has been implicated in other cancer types; for example RUNX1 and RUNX2 are implicated in cancers of epithelial origin, including prostate, breast, and ovarian cancers.

Safety and efficacy of oral transmucosal fentanyl citrate for prehospital pain control on the battlefield.

Background: Acute pain, resulting from trauma and other causes, is a common condition that imposes a need for prehospital analgesia on and off the battlefield. The narcotic most frequently used for prehospital analgesia on the battlefield during the past century has been morphine. Intramuscular morphine has a delayed onset of pain relief that is suboptimal and difficult to titrate.

Translational advances in pain and anesthesia for cancer patients.

Effective cancer pain management requires multidisciplinary approaches for multimodal analgesia. Although opioids have been the cornerstone, developments such as regional anesthesia and interventional pain techniques, complementary and alternative medicine, and new pharmaceuticals also have shown promise to relieve cancer pain. This overview of relevant clinical efforts and the modern day state of the science will afford a better understanding of pain mechanisms and multimodal approaches beneficial in optimizing analgesia for cancer patients.

Relationships between early acute pain scores, autonomic nervous system function, and injury severity in wounded soldiers.

Background: Acute pain after injury affects the comfort and function of the wounded soldier and the physiology of multiple body systems. In the civilian population, pain alters the function of the autonomic nervous system, causing increased heart rate and blood pressure. However, there are no data regarding the impact of combat-related pain on physiologic responses.

Combining ketamine and virtual reality pain control during severe burn wound care: one military and one civilian patient.

Background: US soldiers injured in Iraq, and civilian burn trauma patients are treated at the US Army Institute of Surgical Research. Burn patients experience extreme pain during wound care, and they typically receive opioid analgesics and anxiolytics for debridement. Virtual Reality (VR) has been applied as an adjunct to opioid analgesics for procedural pain.

The relationship of early pain scores and posttraumatic stress disorder in burned soldiers.

Early acute pain after injury has been linked to long-term patient outcomes, including the development of posttraumatic stress disorder (PTSD). Several studies have identified a negative correlation between early anesthetic/analgesic usage and subsequent development of PTSD. This retrospective study examined the relationship between early acute pain and severity of PTSD symptoms in soldiers with burn injuries.

RUNX1 (AML-1) and RUNX2 (AML-3) cooperate with prostate-derived Ets factor to activate transcription from the PSA upstream regulatory region.

The RUNX transcription factors (RUNX1, RUNX2, and RUNX3) play essential roles in hematopoiesis and skeletal development. Consistent with these roles in differentiation and cell cycle, the activity of both RUNX1 and RUNX3 is perturbed in cancer. To determine a role for the RUNX factors in prostate biology, we investigated the expression of RUNX factors in prostate epithelial cell lines and normal prostate tissue.

Translation of the radioresistance kinase TLK1B is induced by gamma-irradiation through activation of mTOR and phosphorylation of 4E-BP1.

Background: The mammalian protein kinase TLK1 is a homologue of Tousled, a gene involved in flower development in Arabidopsis thaliana. The function of TLK1 is not well known, although knockout of the gene in Drosophila, or expression of a dominant negative mutant in mouse cells causes loss of nuclear divisions and chromosome missegregation probably due to alterations in chromatin remodeling capacity. Overexpression of TLK1B, a spliced variant of the TLK1 mRNA, in a model mouse cell line increases their resistance to ionizing radiation, also likely through changes in chromatin remodeling.