NMR Precision Metabolomics: Dynamic Peak Sum Thresholding and Navigators for Highly Standardized and Reproducible Metabolite Profiling of Clinical Urine Samples.

Metabolomics, especially urine-based studies, offers incredible promise for the discovery and development of clinically impactful biomarkers. However, due to the unique challenges of urine, a highly precise and reproducible workflow for NMR-based urine metabolomics is lacking. Using 1D and 2D non-uniform sampled (NUS) H-C NMR spectroscopy, we systematically explored how changes in hydration or specific gravity (SG) and pH can impact biomarker discovery.

Modeling Heartland virus disease in mice and therapeutic intervention with 4'-fluorouridine.

Unlabelled: Heartland virus (HRTV) is an emerging tick-borne bandavirus that causes a febrile illness of varying severity in humans, with cases reported in eastern and midwestern regions of the United States. No vaccines or approved therapies are available to prevent or treat HRTV disease. Here, we describe the genetic changes, natural history of disease, and pathogenesis of a mouse-adapted HRTV (MA-HRTV) that is uniformly lethal in 7- to 8-week-old AG129 mice at low challenge doses.

A model for Scc2p stimulation of cohesin's ATPase and its inhibition by acetylation of Smc3p.

The evolutionarily conserved cohesin complex mediates sister chromatid cohesion and facilitates mitotic chromosome condensation, DNA repair, and transcription regulation. These biological functions require cohesin's two ATPases, formed by the Smc1p and Smc3p subunits. Cohesin's ATPase activity is stimulated by the Scc2p auxiliary factor.

Continuing Orthohantavirus Circulation in Deer Mice in Western Montana.

Hantavirus pulmonary syndrome (HPS) is an often-fatal disease caused by New World hantaviruses, such as (SNV). In the US, >800 cases of HPS have been confirmed since it was first discovered in 1993, of which 43 were reported from the state of Montana. The primary cause of HPS in the US is SNV, which is primarily found in the reservoir host (deer mouse).

Post-Transcriptional Genetic Silencing of to Treat Sickle Cell Disease.

Background: Sickle cell disease is characterized by hemolytic anemia, pain, and progressive organ damage. A high level of erythrocyte fetal hemoglobin (HbF) comprising α- and γ-globins may ameliorate these manifestations by mitigating sickle hemoglobin polymerization and erythrocyte sickling. is a repressor of γ-globin expression and HbF production in adult erythrocytes.

Host Competency of the Multimammate Rat Demonstrated by Prolonged Spirochetemias with the African Relapsing Fever Spirochete .

African multimammate rats, , are widely distributed in sub-Saharan Africa and live in close association with humans. In West Africa, numerous field studies have shown these animals may be naturally infected with the relapsing fever spirochete , the primary cause of tick-borne relapsing fever in this region of the continent. However, naturally infected individual rats have never been examined over time; therefore, the true host competency of these rats for this spirochete is unknown.

Impact of Department of Veterans Affairs Cooperative Studies Program clinical trials on practice guidelines for high blood pressure management.

Knowing the extent to which a clinical trial's findings translate into clinical practice can be challenging. One practical approach to estimating a trial's influence on clinical practice can be achieved by assessing how the trial informed relevant clinical practice guidelines (CPGs). Accordingly, the objectives of this study were to provide an overview of all the clinical trials involving the Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) that aimed at informing or resulted in informing the management of high blood pressure and to identify and describe the extent to which these trials informed CPGs for the management of high blood pressure.

Total integrated performance excellence system (TIPES): A true north direction for a clinical trial support center.

This paper presents the quality journey taken by a Federal organization over more than 20 years. These efforts have resulted in the implementation of a Total Integrated Performance Excellence System (TIPES) that combines key principles and practices of established quality systems. The Center has progressively integrated quality system frameworks including the Malcom Baldrige National Quality Award (MBNQA) Framework and Criteria for Performance Excellence, ISO 9001, and the Organizational Project Management Maturity Model (OPM3), as well as supplemental quality systems of ISO 15378 (packaging for medicinal products) and ISO 21500 (guide to project management) to systematically improve all areas of operations.

The role of ixazomib as an augmented conditioning therapy in salvage autologous stem cell transplant (ASCT) and as a post-ASCT consolidation and maintenance strategy in patients with relapsed multiple myeloma (ACCoRd [UK-MRA Myeloma XII] trial): study protocol for a Phase III randomised controlled trial.

Background: Multiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT).

Using Video Stimuli to Examine Judgments of Nonoffending and Offending Pedophiles: A Brief Communication.

In this experimental study, 89 participants were allocated to an offending pedophile, nonoffending pedophile, or control video condition. They then watched two short help-seeking video clips of an older male and a younger male (counterbalanced). Judgments about each male were assessed, as were general attitudes toward pedophiles and sexual offenders.

Colonoscopy vs. Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM): Rationale for Study Design.

Rationale: Colorectal cancer (CRC) is preventable through screening, with colonoscopy and fecal occult blood testing comprising the two most commonly used screening tests. Given the differences in complexity, risk, and cost, it is important to understand these tests' comparative effectiveness.

Study Design: The CONFIRM Study is a large, pragmatic, multicenter, randomized, parallel group trial to compare screening with colonoscopy vs.

Evaluating the Wizards of Motion Cardiovascular Disease Prevention Module.

This study evaluated the level of change in students' knowledge of and attitudes toward healthy lifestyle behaviors and prevention of cardiovascular disease (CVD) following implementation of a Cardiovascular Disease Prevention Module in Grade 5 science classes. Two classes of students ( n = 39) were identified as the intervention group and two classes ( n = 31) were designated as controls. The intervention group participated in the module initially, whereas the control groups participated after the data collection was completed.

Long-term persistence of zoster vaccine efficacy.

Background: The Shingles Prevention Study (SPS) demonstrated zoster vaccine efficacy through 4 years postvaccination. A Short-Term Persistence Substudy (STPS) demonstrated persistence of vaccine efficacy for at least 5 years. A Long-Term Persistence Substudy (LTPS) was undertaken to further assess vaccine efficacy in SPS vaccine recipients followed for up to 11 years postvaccination.

Safety of zoster vaccine in elderly adults following documented herpes zoster.

Background: After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational zoster vaccine without charge. This provided an opportunity to determine the relative safety of zoster vaccine in older adults following documented herpes zoster (HZ).

Methods: A total of 13 681 SPS placebo recipients who elected to receive zoster vaccine were followed for serious adverse events (SAE) for 28 days after vaccination.

Integrating tobacco cessation into mental health care for posttraumatic stress disorder: a randomized controlled trial.

Context: Most smokers with mental illness do not receive tobacco cessation treatment.

Objective: To determine whether integrating smoking cessation treatment into mental health care for veterans with posttraumatic stress disorder (PTSD) improves long-term smoking abstinence rates.

Design, Setting, And Patients: A randomized controlled trial of 943 smokers with military-related PTSD who were recruited from outpatient PTSD clinics at 10 Veterans Affairs medical centers and followed up for 18 to 48 months between November 2004 and July 2009.

Falls assessment and prevention: a multidisciplinary teaching intervention.

Background: Falls are a common and important clinical problem, and with ageing populations worldwide it is important for health care professionals to learn about falls management. The multidisciplinary nature of falls teams also provides an ideal opportunity for interprofessional collaboration in teaching.

Context: In this article, we describe a pilot multidisciplinary falls assessment and prevention workshop for second-year medical students at a London medical school.

Safety of herpes zoster vaccine in the shingles prevention study: a randomized trial.

Background: The herpes zoster vaccine is effective in preventing herpes zoster and postherpetic neuralgia in immunocompetent older adults. However, its safety has not been described in depth.

Objective: To describe local adverse effects and short- and long-term safety profiles of herpes zoster vaccine in immunocompetent older adults.

Clinical features of pulmonary arterial hypertension in young people with an ALK1 mutation and hereditary haemorrhagic telangiectasia.

Background: Pulmonary arterial hypertension (PAH) has been linked to mutations in genes encoding two members of the transforming growth factor-beta family, BMPR2 and ALK1, the latter of which is also associated with hereditary haemorrhagic telangiectasia (HHT). Relatively little is known about the genetics of childhood PAH, or about the clinical features of PAH in young patients with an ALK1 mutation.

Methods And Results: Three individuals diagnosed with PAH at 4, 16 and 17 years of age were found on subsequent genetic screening to have non-synonymous mutations of ALK1.

A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal.

Context: Lofexidine is an alpha-2-adrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine.

Objective: To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally defined opioid withdrawal symptoms in opioid dependent individuals undergoing medically supervised opioid detoxification as compared to placebo.

Characterisation of recombinant human fatty aldehyde dehydrogenase: implications for Sjögren-Larsson syndrome.

Fatty aldehyde dehydrogenase (FALDH) is an NAD+-dependent oxidoreductase involved in the metabolism of fatty alcohols. Enzyme activity has been implicated in the pathology of diabetes and cancer. Mutations in the human gene inactivate the enzyme and cause accumulation of fatty alcohols in Sjögren-Larsson syndrome, a neurological disorder resulting in physical and mental handicaps.