Army and Navy ECHO Pain Telementoring Improves Clinician Opioid Prescribing for Military Patients: an Observational Cohort Study.

Background: Opioid overdose deaths occur in civilian and military populations and are the leading cause of accidental death in the USA.

Objective: To determine whether ECHO Pain telementoring regarding best practices in pain management and safe opioid prescribing yielded significant declines in opioid prescribing.

Design: A 4-year observational cohort study at military medical treatment facilities worldwide.

Persistent hepatitis C viral replication despite priming of functional CD8+ T cells by combined therapy with a vaccine and a direct-acting antiviral.

Unlabelled: Exhaustion of antiviral CD8(+) T cells contributes to persistence of hepatitis C viral (HCV) infection. This immune response has proved difficult to restore by therapeutic vaccination, even when HCV replication is suppressed using antiviral regimens containing type I interferon. Because immunomodulatory effects of type I interferon may be a factor in poor T-cell priming, we undertook therapeutic vaccination in two chronically infected chimpanzees during treatment with a direct-acting antiviral (DAA) targeting the HCV NS5b polymerase protein.

T-cell immunity and hepatitis C virus reinfection after cure of chronic hepatitis C with an interferon-free antiviral regimen in a chimpanzee.

Unlabelled: Memory CD8+ T cells generated by spontaneous resolution of hepatitis C virus (HCV) infection rapidly control secondary infections and reduce the risk of virus persistence. Here, CD8+ T-cell immunity and response to reinfection were assessed in a chimpanzee cured of an earlier chronic infection with an interferon (IFN)-free antiviral regimen. CD8+ T cells expanded from liver immediately before and 2 years after cure of chronic infection with two direct-acting antivirals (DAAs) targeted epitopes in the E2, nonstructural (NS)5a, and NS5b proteins.

Immunotherapy of chronic hepatitis C virus infection with antibodies against programmed cell death-1 (PD-1).

Hepatitis C virus (HCV) persistence is facilitated by exhaustion of CD8+ T cells that express the inhibitory receptor programmed cell death 1 (PD-1). Blockade of PD-1 signaling improves in vitro proliferation of HCV-specific T lymphocytes, but whether antiviral function can be restored in infected individuals is unknown. To address this question, chimpanzees with persistent HCV infection were treated with anti-PD-1 antibodies.

Obstructive uropathy secondary to uterine leiomyoma in a chimpanzee (Pan troglodytes).

Complications due to uterine leiomyomata in chimpanzees have rarely been documented. Here we describe a female chimpanzee that developed severe hydronephrosis in the right kidney due to leiomyoma. Because hysterectomy did not alleviate the hydronephrosis, nephrectomy was elected.

Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models.

Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1-6 and determined the infectivity titer of acute-phase plasma pools in additional animals. The courses of first- and second-passage infections were similar, with early appearance of viremia, HCV RNA titers of >10(4.

Novel infectious cDNA clones of hepatitis C virus genotype 3a (strain S52) and 4a (strain ED43): genetic analyses and in vivo pathogenesis studies.

Previously, RNA transcripts of cDNA clones of hepatitis C virus (HCV) genotypes 1a (strains H77, HCV-1, and HC-TN), 1b (HC-J4, Con1, and HCV-N), and 2a (HC-J6 and JFH1) were found to be infectious in chimpanzees. However, only JFH1 was infectious in human hepatoma Huh7 cells. We performed genetic analysis of HCV genotype 3a (strain S52) and 4a (strain ED43) prototype strains and generated full-length consensus cDNA clones (pS52 and pED43).

In vivo bone formation in silk fibroin and chitosan blend scaffolds via ectopically grafted periosteum as a cell source: a pilot study.

Reconstruction of a critical size bone defect in the head and neck after trauma or tumor resection remains challenging. While certain defects, such as isolated orbital floor fractures, may be reconstructed with alloplastic biomaterials, larger defects or those involving load bearing bones usually require autologous tissue reconstruction. Vascularized bone free flaps remain the gold standard for large bone defects of the head and neck.

Use of vascularized periosteum or bone to improve healing of segmental allografts after tumor resection: an ovine rib model.

Background: Despite technical advances, nonunion or delayed union remains an important clinical problem when segmental allografts are used to repair diaphyseal defects after bone tumor resection. Using an ovine rib model, the authors studied whether the addition of a vascularized periosteum or bone flap improved healing compared with a segmental allograft alone.

Methods: A 4-cm segment of rib was resected from four consecutive ribs of 15 sheep.

Previously infected chimpanzees are not consistently protected against reinfection or persistent infection after reexposure to the identical hepatitis C virus strain.

Protective immunity after resolved hepatitis C virus (HCV) infection has been reported. However, the breadth of this immunity has remained controversial, and the role of neutralizing antibodies has not been well-defined. In the present study, two chimpanzees (CH96A008 and CH1494) with resolved monoclonal H77C (genotype 1a) infection were rechallenged with low-dose homologous H77C virus about 12 months after viral clearance; CH96A008 became persistently infected, and CH1494 had transient viremia lasting 2 weeks.

Sleep disturbance during military deployment.

This preliminary investigation evaluated symptoms of sleep disturbance and insomnia in a group of 156 deployed military personnel. A 21-item Military Deployment Survey of Sleep was administered to provide self-reported estimates of a variety of sleep parameters. The results indicated that 74% of participants rated their quality of sleep as significantly worse in the deployed environment, 40% had a sleep efficiency of < 85%, and 42% had a sleep onset latency of > 30 minutes.

Sheep stromal-epithelial cell interactions and ovarian tumor progression.

Previous studies suggest that underlying ovarian stromal cues may regulate the ovarian surface epithelium. However, little is known about the interaction between ovarian stromal cells (OSC) and ovarian surface epithelial cells (OSE) under normal physiologic and pathologic conditions, largely because of the lack of a suitable model. In the current study, the OSC obtained from a sheep were immortalized with SV-40 T/t antigen (designated IOSC) and telomerase reverse transcriptase (designated IOSCH), followed by transfection with the oncogenic allele of the human H-Ras oncogene (designated IOSChR).

Characterization of chimpanzee/human monoclonal antibodies to vaccinia virus A33 glycoprotein and its variola virus homolog in vitro and in a vaccinia virus mouse protection model.

Three distinct chimpanzee Fabs against the A33 envelope glycoprotein of vaccinia virus were isolated and converted into complete monoclonal antibodies (MAbs) with human gamma 1 heavy-chain constant regions. The three MAbs (6C, 12C, and 12F) displayed high binding affinities to A33 (K(d) of 0.14 nM to 20 nM) and may recognize the same epitope, which was determined to be conformational and located within amino acid residues 99 to 185 at the C terminus of A33.

Comparison of guided bone formation from periosteum and muscle fascia.

Background: Muscle fascia and periosteum have been used clinically to guide prefabrication of vascularized bone flaps for reconstruction of complex three-dimensional tissues. Although it seems that both locations have the capacity to generate vascularized bone, there have been no studies that directly compare different implantation sites. The authors performed a rigorous, quantitative, histomorphometric comparison of bone prefabrication in a large-animal model comparing graft implanted against muscle fascia and periosteum.

Combination of 4-HPR and oral contraceptive in monkey model of chemoprevention of ovarian cancer.

4-(N-hydroxyphenyl) retinamide (4-HPR) and the oral contraceptives (OCP) are currently being used alone, and in combination, for the prevention of ovarian cancer. However, the mechanism of their effects has not been studied. Non-human primate models are ideal for studying the role of these and other drugs for cancer chemoprevention because of the genetic similarity between primates and humans in respect to hormone regulation and menstrual cycle.

Assessment of cyclic changes of microvessels in ovine ovaries using Sonovue contrast-enhanced ultrasound.

Our objective was to detect variations of ovarian vascularization that occur in the estrus cycle of the ewe using an IV contrast agent. Five ewes were investigated using contrast-enhanced power Doppler after Sonovue injection at day 0, 3, 5, 10 and 13 of the cycle in two successive estrus cycles. Transvaginal ultrasound monitoring of each ewe was performed after a dose of Sonovue.

Chimpanzee/human mAbs to vaccinia virus B5 protein neutralize vaccinia and smallpox viruses and protect mice against vaccinia virus.

Chimpanzee Fabs against the B5 envelope glycoprotein of vaccinia virus were isolated and converted into complete mAbs with human gamma 1 heavy chain constant regions. The two mAbs (8AH8AL and 8AH7AL) displayed high binding affinities to B5 (Kd of 0.2 and 0.

Immune responses to repetitive adenovirus-mediated gene transfer and restoration of gene expression by cyclophosphamide or etoposide.

Background: One major concern about adenoviral vectors for repetitive gene delivery is the induction of an immune response to the vector, thus impeding effective gene transduction.

Methods: To assess the immune response to the adenoviral vector, repetitive gene dosing was performed into rhesus monkey cervix and C3H mouse skin using the adenoviral vector carrying the lacZ gene. Three repetitive intracervical injections of adenovirus-lacZ were done in the rhesus monkey at the intervals of 4 weeks.

Arthroscopic patellar "bankart" repair after acute dislocation.

We present a case of acute patellar dislocation in a skeletally immature patient treated with arthroscopic medial patellofemoral ligamentous complex repair using suture anchors with a horizontal mattress suture technique. Patellar dislocation is a common problem in the skeletally immature. Treatment is controversial for first-time dislocators because of the high rate of recurrent instability and functional disability in these patients.

Ovine model to evaluate ovarian vascularization by using contrast-enhanced sonography.

This project was designed to evaluate an ovine model for the use of contrast agent to visualize the microcirculation of normal ovaries. Intraovarian vascularization was investigated in eight ewes by using contrast-enhanced power Doppler after intravenous injection of Sonovue at five different times during each of ten normal estrous cycles. Sheep under general anesthesia underwent transvaginal B mode and power Doppler ultrasound examination of both ovaries, then received two successive doses of 5 ml of Sonovue, one dose for each ovary.

Ovine model for engineering bone segments.

We propose a large animal model for bone tissue engineering that yields quantitative data and simulates clinical methods and tissue needs. Skeletally mature domestic sheep (n = 20) were each implanted with three rectangular (1 x 1 x 4 cm), hollow tissue-molding chambers that were empty (control) or filled with equal weights (6.71-6.

Safety of continuous intrathecal midazolam infusion in the sheep model.

Unlabelled: We investigated the safety of midazolam administered by continuous intrathecal infusion in relevant animal models. Preservative-free midazolam was delivered to sheep and pigs by using implanted infusion systems (SynchroMed pumps plus silicone catheters). Sheep received midazolam 5 mg/d (n = 4) or 15 mg/d (n = 7) or saline (n = 2) for 43 days at 125 micro L/h.

Continuous intrathecal infusion of hydromorphone: safety in the sheep model and clinical implications.

Objective: To determine the safety of hydromorphone delivered by continuous intrathecal infusion via implanted delivery systems in sheep.

Design: Sheep implanted with intrathecal infusion systems were randomly assigned to receive either 1.5, 3, or 6 mg/day hydromorphone HCl or saline control (3 sheep/dose level) at a fixed infusion rate of 1.

Safety of chronic intrathecal morphine infusion in a sheep model.

Background: The safety of chronically administered intrathecal morphine has been questioned. Therefore, the authors examined the behavioral and neurologic effects and neurotoxicity of continuous intrathecal morphine administration in sheep.

Methods: Groups of three sheep were implanted with intrathecal infusion systems for the continuous administration of morphine (3, 6, 9, 12, or 18 mg/day) or saline at a fixed infusion rate of 1.