A probabilistic intake model to estimate the impact of reformulation by the food industry among Irish consumers.

This project quantified the impact that voluntary reformulation efforts of the food industry had on the Irish population's nutrient intake. Nutrient composition data on reformulated products were collected from 14 major food companies for two years, 2005 and 2012. Probabilistic intake assessments were performed using the Irish national food consumption surveys as dietary intake data.

Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy.

Background: Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA).

Methods: We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age.

Normal interventricular differences in tissue architecture underlie right ventricular susceptibility to conduction abnormalities in a mouse model of Brugada syndrome.

Aims: Loss-of-function of the cardiac sodium channel NaV1.5 is a common feature of Brugada syndrome. Arrhythmias arise preferentially from the right ventricle (RV) despite equivalent NaV1.

Association of Opioid Usage with Spinal Cord Stimulation Outcomes.

Study Design: Observational study using insurance claims.

Objective: To quantify opioid usage leading up to spinal cord stimulation (SCS) and the potential impact on outcomes of SCS.

Setting: SCS is an interventional therapy that often follows opioid usage in the care continuum for chronic pain.

Multiplexed in vivo homology-directed repair and tumor barcoding enables parallel quantification of Kras variant oncogenicity.

Large-scale genomic analyses of human cancers have cataloged somatic point mutations thought to initiate tumor development and sustain cancer growth. However, determining the functional significance of specific alterations remains a major bottleneck in our understanding of the genetic determinants of cancer. Here, we present a platform that integrates multiplexed AAV/Cas9-mediated homology-directed repair (HDR) with DNA barcoding and high-throughput sequencing to simultaneously investigate multiple genomic alterations in de novo cancers in mice.

Natural history of infantile-onset spinal muscular atrophy.

Objective: Infantile-onset spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality, typically resulting in death preceding age 2. Clinical trials in this population require an understanding of disease progression and identification of meaningful biomarkers to hasten therapeutic development and predict outcomes.

Methods: A longitudinal, multicenter, prospective natural history study enrolled 26 SMA infants and 27 control infants aged <6 months.

Hi-fidelity discrimination of isomiRs using G-quadruplex gatekeepers.

Core microRNA (miRNA) sequences exist as populations of variants called isomiRs made up of different lengths and nucleotide compositions. In particular, the short sequences of miRNA make single-base isomiR mismatches very difficult to be discriminated. Non-specific hybridizations often arise when DNA probe-miRNA target hybridization is the primary, or initial, mode of detection.

Using Simulation to Hardwire Bedside Shift Report.

Numerous attempts to move nursing handoff to the bedside failed within our organization. Upon retrospect, previous attempts lacked standardization, coordination, and clear expectations. With emphasis on implementing patient- and family-centered care to increase patient experience scores, we developed a standardized staff training methodology using didactic and simulation to address staff barriers to adoption, a standardized implementation process, and a process to hardwire the practice.

Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy.

Background: Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein.

Methods: We conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy.

Diverse Peptide Hormones Affecting Root Growth Identified in the Secreted Peptidome.

Multigene families encoding diverse secreted peptide hormones play important roles in plant development. A need exists to efficiently elucidate the structures and post-translational-modifications of these difficult-to-isolate peptide hormones so that their biological functions can be determined. A mass spectrometry and bioinformatics approach was developed to comprehensively analyze the secreted peptidome of hairy root cultures and xylem sap.

Baseline Understanding of Urinary Incontinence and Prolapse in New Urogynecology Patients.

Objectives: Investigators sought to assess whether age was related to patient understanding of pelvic floor disorders; given studies show that increased age is associated with lower health literacy.

Methods: This was a cross-sectional survey of new urogynecology patients. Enrolled participants completed a survey including demographics, history of urinary incontinence (UI) and pelvic organ prolapse symptoms and treatment, the Prolapse and Incontinence Knowledge Questionnaire (PIKQ), self-assessment of UI and prolapse knowledge, and a pelvic anatomy diagram to label.

A hybrid type Ia supernova with an early flash triggered by helium-shell detonation.

Type Ia supernovae arise from the thermonuclear explosion of white-dwarf stars that have cores of carbon and oxygen. The uniformity of their light curves makes these supernovae powerful cosmological distance indicators, but there have long been debates about exactly how their explosion is triggered and what kind of companion stars are involved. For example, the recent detection of the early ultraviolet pulse of a peculiar, subluminous type Ia supernova has been claimed as evidence for an interaction between a red-giant or a main-sequence companion and ejecta from a white-dwarf explosion.

Highly trabeculated structure of the human endocardium underlies asymmetrical response to low-energy monophasic shocks.

Novel low-energy defibrillation therapies are thought to be driven by virtual-electrodes (VEs), due to the interaction of applied monophasic electric shocks with fine-scale anatomical structures within the heart. Significant inter-species differences in the cardiac (micro)-anatomy exist, however, particularly with respect to the degree of endocardial trabeculations, which may underlie important differences in response to low-energy defibrillation protocols. Understanding the interaction of monophasic electric fields with the specific human micro-anatomy is therefore imperative in facilitating the translation and optimisation of these promising experimental therapies to the clinic.

Surgical Skills Feedback and myTIPreport: Is There Construct Validity?

Objective: To initiate construct validity testing of myTIPreport for procedural skill assessment in a prospective multicenter evaluation study.

Methods: Teachers and learners from a convenience-based site selection of obstetrics and gynecology (OBGYN) and female pelvic medicine and reconstructive surgery (FPMRS) training programs performed procedural assessments in myTIPreport. The specifically defined 5-point Dreyfus rating scale describing ability levels from novice to expert was used.

Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics.

There is growing interest in using embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful.

Early Development of Right Ventricular Ischemic Lesions in a Novel Large Animal Model of Acute Right Heart Failure in Chronic Thromboembolic Pulmonary Hypertension.

Background: Our aim was to develop a model of acute right heart failure (ARHF) in the setting of pulmonary hypertension and to characterize acute right ventricular lesions that develop early after hemodynamic restoration.

Methods And Results: We used a described piglet model of chronic pulmonary hypertension (cPH) induced by pulmonary artery occlusions. We induced ARHF in animals with cPH (ARHF-cPH group, n = 9) by volume loading and iterative acute pulmonary embolism until hemodynamic compromise followed by dobutamine infusion for hemodynamic restoration before sacrifice for right ventricular tissue evaluation.

Overcoming Operational Challenges to Ebola Case Investigation in Sierra Leone.

The Ebola virus disease (EVD) epidemic that hit West Africa in 2013 was the worst outbreak of EVD in recorded history. While much has been published regarding the international and national-level EVD responses, there is a dearth of literature on district-level coordination and operational structures, successes, and failures. This article seeks to understand how the EVD response unfolded at the district level, namely the challenges to operationalizing EVD surveillance over the course of the outbreak in Port Loko and Kambia districts of Sierra Leone.

Exposure assessment using human biomonitoring for glyphosate and fluroxypyr users in amenity horticulture.

Background: Pesticides and their potential adverse health effects are of great concern and there is a dearth of knowledge regarding occupational exposure to pesticides among amenity horticulturalists.

Objective: This study aims to measure occupational exposures to amenity horticuturalists using pesticides containing the active ingredients, glyphosate and fluroxypyr by urinary biomonitoring.

Methods: A total of 40 work tasks involving glyphosate and fluroxypyr were surveyed over the period of June - October 2015.

Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary.

Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

Brief Report: External Beam Radiation Therapy for the Treatment of Human Pluripotent Stem Cell-Derived Teratomas.

Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs), have great potential as an unlimited donor source for cell-based therapeutics. The risk of teratoma formation from residual undifferentiated cells, however, remains a critical barrier to the clinical application of these cells. Herein, we describe external beam radiation therapy (EBRT) as an attractive option for the treatment of this iatrogenic growth.

Attention Selectively Reshapes the Geometry of Distributed Semantic Representation.

Humans prioritize different semantic qualities of a complex stimulus depending on their behavioral goals. These semantic features are encoded in distributed neural populations, yet it is unclear how attention might operate across these distributed representations. To address this, we presented participants with naturalistic video clips of animals behaving in their natural environments while the participants attended to either behavior or taxonomy.

PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity.

Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that is upregulated on activated T cells for the induction of immune tolerance. Tumour cells frequently overexpress the ligand for PD-1, programmed cell death ligand 1 (PD-L1), facilitating their escape from the immune system. Monoclonal antibodies that block the interaction between PD-1 and PD-L1, by binding to either the ligand or receptor, have shown notable clinical efficacy in patients with a variety of cancers, including melanoma, colorectal cancer, non-small-cell lung cancer and Hodgkin's lymphoma.

Newborn screening for Duchenne muscular dystrophy in China: follow-up diagnosis and subsequent treatment.

Background: Newborn screening for Duchenne muscular dystrophy (DMD) is currently being initiated in Zhejiang Province, China and is under consideration in other countries, including the United States. As China begins to implement DMD newborn screening (DMD-NBS), there is ongoing discussion regarding the steps forward for follow up care of positively identified patients as well as false positive and false negative results.

Data Sources: Relevant papers related to DMD-NBS, and NBS in China were reviewed in PubMed.

Long-term miR-29b suppression reduces aneurysm formation in a Marfan mouse model.

Aortic root aneurysm formation and subsequent dissection and/or rupture remain the leading cause of death in patients with Marfan syndrome. Our laboratory has reported that miR-29b participates in aortic root/ascending aorta extracellular matrix remodeling during early aneurysm formation in Marfan mice. Herein, we sought to determine whether miR-29b suppression can reduce aneurysm formation long-term.