Proc Natl Acad Sci U S A
March 2012
Antibody therapies to prevent or limit filovirus infections have received modest interest in recent years, in part because of early negative experimental evidence. We have overcome the limitations of this approach, leveraging the use of antibody from nonhuman primates (NHPs) that survived challenge to filoviruses under controlled conditions. By using concentrated, polyclonal IgG antibody from these survivors, we treated filovirus-infected NHPs with multiple doses administered over the clinical phase of disease.
View Article and Find Full Text PDFEbola and Marburg filoviruses cause deadly outbreaks of haemorrhagic fever. Despite considerable efforts, no essential cellular receptors for filovirus entry have been identified. We showed previously that Niemann-Pick C1 (NPC1), a lysosomal cholesterol transporter, is required for filovirus entry.
View Article and Find Full Text PDFIEEE Int Conf Rehabil Robot
July 2012
We present an application of a socially assistive robotics (SAR) system in a therapeutic setting. We examine the amount of interaction elicited by the robot in a therapeutic setting with individuals post-stroke. We examine the role of various communication modalities, and their affects on the participants' responses.
View Article and Find Full Text PDFIrregular vestibular afferents exhibit significant phase leads with respect to angular velocity of the head in space. This characteristic and their connectivity with vestibulospinal neurons suggest a functionally important role for these afferents in producing the vestibulo-collic reflex (VCR). A goal of these experiments was to test this hypothesis with the use of weak galvanic stimulation of the vestibular periphery (GVS) to selectively activate or suppress irregular afferents during passive whole body rotation of guinea pigs that could freely move their heads.
View Article and Find Full Text PDFAntibody 14G7 is protective against lethal Ebola virus challenge and recognizes a distinct linear epitope in the prominent mucin-like domain of the Ebola virus glycoprotein GP. The structure of 14G7 in complex with its linear peptide epitope has now been determined to 2.8 Å.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2011
Ebola hemorrhagic fever is an acute and often deadly disease caused by Ebola virus (EBOV). The possible intentional use of this virus against human populations has led to design of vaccines that could be incorporated into a national stockpile for biological threat reduction. We have evaluated the immunogenicity and efficacy of an EBOV vaccine candidate in which the viral surface glycoprotein is biomanufactured as a fusion to a monoclonal antibody that recognizes an epitope in glycoprotein, resulting in the production of Ebola immune complexes (EICs).
View Article and Find Full Text PDFSudan virus (genus Ebolavirus) is lethal, yet no monoclonal antibody is known to neutralize it. We here describe antibody 16F6 that neutralizes Sudan virus and present its structure bound to the trimeric viral glycoprotein. Unexpectedly, the 16F6 epitope overlaps that of KZ52, the only other antibody against the GP(1,2) core to be visualized to date.
View Article and Find Full Text PDFBackground: Post-transplantation primary central nervous system lymphoma (PT-PCNSL) is a rare neoplasm that can develop within months to years after transplantation, and imaging often reveals multiple lesions with homogeneous or ring enhancement. The clinical and imaging presentation of PT-PCNSL can often be nonspecific and present a diagnostic challenge.
Case Description: A 56-year-old woman presented to a tertiary university emergency room with altered mental status 15 months after undergoing renal transplantation.
Objective: To determine practice outcomes associated with doctor of pharmacy (PharmD) graduates from 2 universities who completed a diabetes-concentration.
Methods: An online survey instrument was sent to 93 PharmD graduates who completed a concentration in diabetes and 94 control graduates to determine their knowledge of and skills in providing diabetes care and how frequently they provided diabetes care services.
Results: Ninety-seven graduates (52%) responded.
Infections by the Ebola and Marburg filoviruses cause a rapidly fatal haemorrhagic fever in humans for which no approved antivirals are available. Filovirus entry is mediated by the viral spike glycoprotein (GP), which attaches viral particles to the cell surface, delivers them to endosomes and catalyses fusion between viral and endosomal membranes. Additional host factors in the endosomal compartment are probably required for viral membrane fusion; however, despite considerable efforts, these critical host factors have defied molecular identification.
View Article and Find Full Text PDFSevere skin loss constitutes a major unsolved clinical problem worldwide. For this reason, in the last decades there has been a major push towards the development of novel therapeutic approaches to enhance skin wound healing. Neo-vessel formation through angiogenesis is a critical step during the wound healing process.
View Article and Find Full Text PDFMedulloblastomas (MB) are highly aggressive primitive neuroectodermal tumors (PNET) usually located in the posterior fossa. Current treatment for MBs, which includes a combination of surgery, chemotherapy and radiation, remain challenging especially in younger patients. However, advances in the understanding of regulatory pathways in cerebellar development have elucidated possible areas of dysfunction involved in tumorigenesis.
View Article and Find Full Text PDFBackground: This study compares open tibia fractures in US Navy and US Marine Corps casualties from the current conflicts with those from a civilian Level I trauma center to analyze the effect of blast mechanism on limb-salvage rates.
Methods: Data from the 28,646 records in the University of California San Diego Trauma Registry from 1985 to 2006 was compared with 2,282 records from the US Navy and US Marine Corps Combat Trauma Registry Expeditionary Medical Encounter Database for the period of March 2004 to August 2007. Injuries were categorized by Gustilo-Anderson (G-A) open fracture classification.
Although patients with cerebral cavernous malformations may remain asymptomatic, they often present with neurological symptoms of headache, hemorrhage and, most commonly, seizure. A review of articles published between 1985 and 2009 was performed to elucidate the prognostic factors which may predict post-operative seizure control. The following characteristics were found to consistently correlate with a more favorable post-operative seizure-free outcome: (i) extent of resection of the cavernous malformation and its surrounding hemosiderin rim; (ii) single or sporadic seizures compared to chronic epilepsy; (iii) illness duration less than 1 or 2 years; and (iv) size of cavernous malformation less than 1.
View Article and Find Full Text PDFFiloviruses can cause severe and often fatal hemorrhagic fever in humans and non-human primates (NHPs). Although there are currently no clinically proven treatments for filovirus disease, much progress has been made in recent years in the discovery of therapeutics and vaccines against these viruses. A variety of vaccine platforms have been shown to be effective against filovirus infection.
View Article and Find Full Text PDFCalcium ions are utilized in biomolecular biomaterial design for osteomimetic scaffolds and as divalent cross-linking agents, typically for gelation of alginates, stabilisation of protein structure (e.g., fibrinogen) and enzyme activation (e.
View Article and Find Full Text PDFBackground: The use of temporary vascular shunts (TVS)s in the management of wartime extremity vascular injuries has received an increasing amount of attention. However, the overall impact of this adjunct remains incompletely defined. The objective of this study is to characterize outcomes of those patients who suffered wartime extremity vascular injuries managed with TVSs.
View Article and Find Full Text PDFBackground: Approximately 30,000 people are diagnosed with oral cancer annually in the United States. Recent evidence suggests that nutrition may play a more complex role in the prevention of oral cancers than previously believed. Proanthocyanidins (PACs) are a class of compounds found in normal dietary foods that exhibit chemopreventive properties and chemotherapeutic potential.
View Article and Find Full Text PDFBackground: Combat injury patterns differ from civilian trauma in that the former are largely explosion-related, comprising multiple mechanistic and fragment injuries and high-kinetic-energy bullets. Further, unlike civilians, U.S.
View Article and Find Full Text PDFExposure to traffic-related ambient air pollution, such as diesel exhaust particles (DEP), is associated with adverse health outcomes, especially in individuals with preexisting inflammatory respiratory diseases. Using an analogous novel in vitro system to model both the healthy and inflamed lung, the susceptibility of epithelial cells exposed to DEP of varying organic carbon content was studied. Murine LA-4 alveolar type II-like epithelial cells, as well as primary murine tracheal epithelial cells (MTE), were treated with exogenous cytokines (tumor necrosis factor [TNF] alpha + interleukin [IL]-1 beta + interferon [IFN] gamma) to model a mild inflammatory state.
View Article and Find Full Text PDFEbola viruses are highly pathogenic viruses that cause outbreaks of hemorrhagic fever in humans and other primates. To meet the need for a vaccine against the several types of Ebola viruses that cause human diseases, we developed a multivalent vaccine candidate (EBO7) that expresses the glycoproteins of Zaire ebolavirus (ZEBOV) and Sudan ebolavirus (SEBOV) in a single complex adenovirus-based vector (CAdVax). We evaluated our vaccine in nonhuman primates against the parenteral and aerosol routes of lethal challenge.
View Article and Find Full Text PDFBackground: Recombinant activated human coagulation factor VII (rFVIIa), an intravascular strategy to promote clotting, is being used as an adjunct to surgical control of bleeding in combat trauma patients.
Objective: To describe the initial experiences with rFVIIa administered to combat casualties at US Navy-Marine Corps medical treatment facilities in Iraq, and to compare survival outcomes of those treated with rFVIIa to controls not receiving rFVIIa.
Methods: Medical encounter data from the US Navy-Marine Corps Combat Trauma Registry were retrospectively reviewed to identify all battle-injured patients documented as having received rFVIIa during the period May 2004 to January 2006 of Operation Iraqi Freedom.
Study Design: Case report.
Objective: To describe an alternative treatment approach for piriformis syndrome using a hip muscle strengthening program with movement reeducation.
Background: Interventions for piriformis syndrome typically consist of stretching and/or soft tissue massage to the piriformis muscle.
Background: Post-traumatic stress disorder (PTSD) is a common adverse mental health outcome among seriously injured civilians and military personnel who are survivors of trauma. Pharmacotherapy in the aftermath of serious physical injury or exposure to traumatic events may be effective for the secondary prevention of PTSD.
Methods: We identified 696 injured U.