A Randomized, Placebo-Controlled, Respiratory Syncytial Virus Human Challenge Study of the Antiviral Efficacy, Safety, and Pharmacokinetics of RV521, an Inhibitor of the RSV-F Protein.

Effective treatments for respiratory syncytial virus (RSV) infection are lacking. Here, we report a human proof-of-concept study for RV521, a small-molecule antiviral inhibitor of the RSV-F protein. In this randomized, double-blind, placebo-controlled trial, healthy adults were challenged with RSV-A Memphis-37b.

Respiratory syncytial virus-A dynamics and the effects of lumicitabine, a nucleoside viral replication inhibitor, in experimentally infected humans.

Background: Respiratory syncytial virus (RSV) causes high morbidity, with mortality rates approaching or exceeding that of influenza in adult and infant patient populations, respectively. Lumicitabine (ALS-008176 or JNJ-64041575) is an oral nucleoside analogue prodrug in clinical development to treat RSV infections. This prodrug converts to plasma-circulating ALS-8112, and then to the 5'-active nucleoside triphosphate (NTP) form within host cells.

Comparison of antiviral resistance across acute and chronic viral infections.

Antiviral therapy can lead to drug resistance, but multiple factors determine the frequency of drug resistance mutations and the clinical consequences. When chronic infections caused by Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) are compared with acute infections such as influenza virus, respiratory syncytial virus (RSV), and other respiratory viruses, there are similarities in how and why antiviral resistance substitutions occur, but the clinical significance can be quite different. Emergence of resistant variants has implications for design of new therapeutics, treatment guidelines, clinical trial design, resistance monitoring, reporting, and interpretation.

Absolute Versus Relative Fracture Fixation: Impact on Fracture Healing.

The goals of all orthopaedic surgeons treating fractures are, and will remain, obtaining union of the fracture with a well-aligned and functional limb while minimizing the risk of complications. This requires us to understand how the biomechanical environment of the fracture affects healing and to be able to discern which mechanical environment is preferred over another. Understanding the spectrum of stability imparted by our current surgical devices is paramount to giving our patients the best opportunity to heal and recover from their injury.

Identifying Gaps in Respiratory Syncytial Virus Disease Epidemiology in the United States Prior to the Introduction of Vaccines.

Respiratory syncytial virus (RSV) causes lower respiratory tract illness frequently. No effective antivirals or vaccines for RSV are approved for use in the United States; however, there are at least 50 vaccines and monoclonal antibody products in development, with those targeting older adults and pregnant women (to protect young infants) in phase 2 and 3 clinical trials. Unanswered questions regarding RSV epidemiology need to be identified and addressed prior to RSV vaccine introduction to guide the measurement of impact and future recommendations.

A human challenge model for respiratory syncytial virus kinetics, the pharmacological effect of a novel fusion inhibitor, and the modelling of symptoms scores.

Respiratory syncytial virus (RSV) causes acute lower respiratory tract infections, and is a major cause of hospital admissions and death in young children. Limited treatments currently exist that can prevent or minimise exacerbation of the disease. The aims of this work were: 1) to develop a population pharmacodynamic model to describe RSV kinetics (RSVK) in nasal lavage, 2) evaluate the impact of an investigational fusion inhibitor, JNJ-53718678, on RSVK, and 3) determine the relationship between RSVK and symptoms scores.

Compassionate use experience with high-titer respiratory syncytical virus (RSV) immunoglobulin in RSV-infected immunocompromised persons.

Background: Respiratory syncytial virus (RSV) may cause fatal lower respiratory tract infection (LRTI) in immunocompromised patients. Ribavirin with or without standard intravenous immunoglobulin (IVIG) is frequently given although efficacy is debated. Infusion of IVIG with high levels of neutralizing antibody against RSV may offer benefit in these patients.

SENTINEL1: An Observational Study of Respiratory Syncytial Virus Hospitalizations among U.S. Infants Born at 29 to 35 Weeks' Gestational Age Not Receiving Immunoprophylaxis.

 SENTINEL1 characterized U.S. preterm infants 29 to 35 weeks' gestational age (wGA) < 12 months old hospitalized for laboratory-confirmed respiratory syncytial virus (RSV) disease and not receiving RSV immunoprophylaxis during the 2014 to 2015 RSV season.

ALN-RSV01 for prevention of bronchiolitis obliterans syndrome after respiratory syncytial virus infection in lung transplant recipients.

Background: Respiratory syncytial virus (RSV) infection in lung transplant (LTx) patients is associated with an increased incidence of bronchiolitis obliterans syndrome (BOS). ALN-RSV01 is a small interfering RNA targeting RSV replication that was shown in an earlier Phase 2a trial to be safe and to reduce the incidence of BOS when compared with placebo.

Methods: We performed a Phase 2b randomized, double-blind, placebo-controlled trial in RSV-infected LTx patients to examine the impact of ALN-RSV01 on the incidence of new or progressive BOS.

Growth in preterm infants fed either a partially hydrolyzed whey or an intact casein/whey preterm infant formula.

Objective: To compare feeding tolerance, nutrient intake and growth in preterm infants (< or =32 weeks, < or =1750 g) fed either a standard nonhydrolyzed whey-casein (nHWC) or a partially hydrolyzed whey (pHW) preterm infant formula.

Study Design: In this double-blind randomized controlled trial infants were fed either formula for at least 3 weeks. Intake was monitored daily, serum chemistries and growth weekly.

Memphis Girls health Enrichment Multi-site Studies (GEMS): Phase 2: design and baseline.

Obesity prevalence is increasing in the U.S., especially among children and minority populations.

Postdischarge nutrition of preterm infants: more questions than answers.

Postnatal growth retardation is inevitable in preterm infants, the more immature the infant the greater the degree of postnatal growth retardation at hospital discharge. After hospital discharge, several studies have shown that growth is poorer in preterm infants fed a standard term formula than those fed a nutrient-enriched infant formula. This is not surprising because term formulas are designed to meet the requirements of the term infant, not the more rapidly growing preterm infant.

Amyloid contained in the knee joint meniscus is formed from apolipoprotein A-I.

Objective: To determine the chemical nature of amyloid deposits found in knee joint menisci.

Methods: Amyloid was extracted from the menisci of 3 adults who underwent knee joint replacement surgery. The primary structural features of the purified proteins were determined by sequential Edman degradation and tandem mass spectrometry (MS/MS).

CaM kinase IIalpha mediates norepinephrine-induced translocation of cytosolic phospholipase A2 to the nuclear envelope.

Several growth factors, hormones and neurotransmitters, including norepinephrine, increase cellular calcium levels, promoting the translocation of cytosolic phospholipase A(2) to the nuclear envelope. This study was conducted to investigate the contributions of the calcium-binding protein calmodulin and of calcium-calmodulin-dependent protein kinase II to cytosolic phospholipase A(2) translocation to the nuclear envelope elicited by norepinephrine in rabbit aortic smooth-muscle cells. Norepinephrine caused cytosolic phospholipase A(2) accumulation around the nuclear envelope as determined from its immunofluorescence; cytosolic phospholipase A(2) translocation was blocked by inhibitors of calmodulin and calcium-calmodulin-dependent protein kinase II or calcium-calmodulin-dependent protein kinase IIalpha antisense oligonucleotide.

Differences and similarities between patients with and without end-stage renal disease, with regard to location of intracardiac calcification.

It has been known for some time that mitral annulus calcification is common in end-stage renal disease (ESRD) patients on long-term dialysis, as well as in elderly patients without renal failure. However, a systematic comparison of cardiac calcification in these two types of patients has not yet been made. We examined two-dimensional echocardiograms in 33 patients with ESRD (mean age 66 +/- 10 years) and in 34 other patients with intracardiac calcification but no ESRD (mean age 69 +/- 9 years), with particular attention to precise anatomic location of calcification.

Characterization of outer membrane proteins in Chlamydia trachomatis LGV serovar L2.

We used a photoactivatable, lipophilic reagent, 3'-(trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine, to label proteins in the outer membrane of elementary bodies of Chlamydia trachomatis LGV serovar L2 and mass spectrometry to identify the labeled proteins. The identified proteins were polymorphic outer membrane proteins E, G, and H, which were made late in the developmental cycle, the major outer membrane protein, and a mixture of 46-kDa proteins consisting of the open reading frame 623 protein and possibly a modified form of the major outer membrane protein.

Identification of polymorphic outer membrane proteins of Chlamydia psittaci 6BC.

The genomes of Chlamydia spp. encode a family of putative outer membrane proteins, referred to as polymorphic outer membrane proteins (POMPs), which may play a role in the avoidance of host immune defenses. We analyzed avian strain 6BC of Chlamydia psittaci by polyacrylamide gel electrophoresis for the expression of POMPs.

20-Hydroxyeicosatetraenoic acid mediates calcium/calmodulin-dependent protein kinase II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells.

Norepinephrine (NE) and angiotensin II (Ang II), by promoting extracellular Ca2+ influx, increase Ca2+/calmodulin-dependent kinase II (CaMKII) activity, leading to activation of mitogen-activated protein kinase (MAPK) and cytosolic phospholipase A2 (cPLA2), resulting in release of arachidonic acid (AA) for prostacyclin synthesis in rabbit vascular smooth muscle cells. However, the mechanism by which CaMKII activates MAPK is unclear. The present study was conducted to determine the contribution of AA and its metabolites as possible mediators of CaMKII-induced MAPK activation by NE, Ang II, and epidermal growth factor (EGF) in vascular smooth muscle cells.

Cytochrome P-450 metabolites mediate norepinephrine-induced mitogenic signaling.

Norepinephrine (NE) stimulates release of arachidonic acid (AA) from tissue lipids in blood vessels, which is metabolized via cyclooxygenase, lipoxygenase (LO), and cytochrome P-450 (CYP-450) pathways to biologically active products. Moreover, NE and AA have been shown to stimulate proliferation of vascular smooth muscle cells (VSMCs) of rat aorta. The purpose of this study was to determine the possible contribution of AA and its metabolites to NE-induced mitogenesis in VSMCs of rat aorta and the underlying mechanism of their actions.

Signal transduction mechanisms involved in angiotensin-(1-7)-stimulated arachidonic acid release and prostanoid synthesis in rabbit aortic smooth muscle cells.

This study investigated the signal transduction mechanisms of angiotensin-(1-7) [Ang-(1-7)]- and Ang II-stimulated arachidonic acid (AA) release for prostaglandin (PG) production in rabbit aortic vascular smooth muscle cells. Ang II and Ang-(1-7) enhanced AA release in cells prelabeled with [3H]AA. However, 6-keto-PGF1 alpha synthesis produced by Ang II was much less than that caused by Ang-(1-7).

The National Cancer Data Base report on recent hospital cancer program progress toward complete American Joint Committee on Cancer/TNM staging.

Background: American Joint Committee on Cancer (AJCC) staging procedures were first published in 1977. Since 1991 the Commission on Cancer (COC) has required AJCC staging of all nonpediatric cancers. The National Cancer Data Base (NCDB) encouraged recording of AJCC staging through analyses of selected aspects of staging completeness.