Efficacy and Safety of OnabotulinumtoxinA for the Treatment of Pediatric Upper and Lower Limb Spasticity: Results From 2 Open-Label, Long-term Extension Trials.

Aim: To evaluate the efficacy and safety of onabotulinumtoxinA for treating upper and lower limb spasticity among pediatric patients in 2 open-label extension trials.

Methods: Patients aged <18 years received ≤5 doses of onabotulinumtoxinA (maximum: 8 U/kg [300 U], cycle 1; 10 U/kg [340 U], cycles 2-5) over 60 weeks. Week 6 efficacy endpoints included mean change from baseline in Modified Ashworth Scale-Bohannon and Modified Tardieu Scale scores, and mean Clinical Global Impression of Overall Change score.

Safety of OnabotulinumtoxinA with Concomitant Antithrombotic Therapy in Patients with Muscle Spasticity: A Retrospective Pooled Analysis of Randomized Double-Blind Studies.

Background: OnabotulinumtoxinA is approved as a treatment across multiple indications. For the treatment of spasticity, onabotulinumtoxinA is injected directly into affected muscles. Intramuscular injections may result in local bleeding and related complications, especially in patients receiving anticoagulant therapy.

OnabotulinumtoxinA for the treatment of major depressive disorder: a phase 2 randomized, double-blind, placebo-controlled trial in adult females.

This 24-week double-blind placebo-controlled multicenter randomized phase 2 trial evaluated efficacy and safety of onabotulinumtoxinA (onabotA; BOTOX) vs. placebo for major depressive disorder (MDD) [NCT02116361]. Primary endpoint was the change in Montgomery-Åsberg Depression Rating Scale (MADRS); secondary endpoints were Clinical Global Impressions-Severity and 17-item Hamilton Depression Rating Scale at week 6.

Trait analysis reveals DOG1 determines initial depth of seed dormancy, but not changes during dormancy cycling that result in seedling emergence timing.

Seedling emergence timing is crucial in competitive plant communities and so contributes to species fitness. To understand the mechanistic basis of variation in seedling emergence timing, we exploited the contrasting behaviour of two Arabidopsis thaliana ecotypes: Cape Verde Islands (Cvi) and Burren (Bur-0). We used RNA-Seq analysis of RNA from exhumed seeds and quantitative trait loci (QTL) analyses on a mapping population from crossing the Cvi and Bur-0 ecotypes.

Outcomes and Economic Benefits of Penn State Extension's Dining With Diabetes Program.

Introduction: Many diabetes education programs address the problem of diabetes, but little attention is given to the economic impact of such programs. Our objective was to assess the effectiveness of a community-based education program in improving diabetes-related lifestyle behaviors and biomarkers and ascertain the economic benefits of the program for adults aged 18 years or older with type 2 diabetes, prediabetes, or no diagnosis of diabetes in Pennsylvania.

Methods: From October 2012 through June 2015, Pennsylvania State University Extension's Dining with Diabetes program collected data on 2,738 adults with type 2 diabetes or prediabetes and adult family members without diabetes.

Trait to gene analysis reveals that allelic variation in three genes determines seed vigour.

Predictable seedling establishment is essential for resource-efficient and cost-effective crop production; it is widely accepted as a critically important trait determining yield and profitability. Seed vigour is essential to this, but its genetic basis is not understood. We used natural variation and fine mapping in the crop Brassica oleracea to show that allelic variation at three loci influence the key vigour trait of rapid germination.

An intra-specific linkage map of lettuce (Lactuca sativa) and genetic analysis of postharvest discolouration traits.

Minimally processed salad packs often suffer from discolouration on cut leaf edges within a few days after harvest. This limits shelf life of the product and results in high wastage. Recombinant inbred lines (RILs) derived from a cross between lettuce cvs.

High-resolution mapping of a fruit firmness-related quantitative trait locus in tomato reveals epistatic interactions associated with a complex combinatorial locus.

Fruit firmness in tomato (Solanum lycopersicum) is determined by a number of factors including cell wall structure, turgor, and cuticle properties. Firmness is a complex polygenic trait involving the coregulation of many genes and has proved especially challenging to unravel. In this study, a quantitative trait locus (QTL) for fruit firmness was mapped to tomato chromosome 2 using the Zamir Solanum pennellii interspecific introgression lines (ILs) and fine-mapped in a population consisting of 7,500 F2 and F3 lines from IL 2-3 and IL 2-4.

A new broccoli × broccoli immortal mapping population and framework genetic map: tools for breeders and complex trait analysis.

A unique broccoli × broccoli doubled haploid (DH) population has been created from the F(1) of a cross between two DH broccoli lines derived from cultivars Green Duke and Marathon. We genotyped 154 individuals from this population with simple sequence repeat and amplified fragment length polymorphism markers to create a B. oleracea L.

Genotype and environment effects on nitrate accumulation in a diversity set of lettuce accessions at commercial maturity: the influence of nitrate uptake and assimilation, osmotic interactions and shoot weight and development.

Background: The causes of the natural variation in nitrate accumulation and associated traits are studied using a diverse population of 48 mature lettuce accessions grown hydroponically in winter and summer seasons. Information on the effects of genotype, environment and their interactions will inform future selection strategies for the production of low-nitrate varieties more suited to meeting EU requirements for harvested produce.

Results: The effects of genotype (G), environment (E) and G × E interactions were all significant, with nitrate concentrations lower but covering a wider range in summer.

Regulation of seed germination in the close Arabidopsis relative Lepidium sativum: a global tissue-specific transcript analysis.

The completion of germination in Lepidium sativum and other endospermic seeds (e.g. Arabidopsis [Arabidopsis thaliana]) is regulated by two opposing forces, the growth potential of the radicle (RAD) and the resistance to this growth from the micropylar endosperm cap (CAP) surrounding it.

Screening for genotype and environment effects on nitrate accumulation in 24 species of young lettuce.

Background: Nitrate accumulates in plants in response to N supply, aerial environment (predominantly light), and genotype. This paper characterises the effects of genotype, environment, and their interactions on nitrate accumulation by 24 cultivated and wild lettuce accessions grown hydroponically in winter and summer. The results will inform future strategies for selecting for low-nitrate varieties.

Meta-analysis of neutralizing antibody conversion with onabotulinumtoxinA (BOTOX®) across multiple indications.

This meta-analysis evaluated the frequency of neutralizing antibody (nAb) conversion with onabotulinumtoxinA (BOTOX®; Allergan) across five studied indications. The analysis was based on large, controlled or prospective, open-label trials (durations 4 months to ≥2 years). Serum samples were analyzed for nAbs using the Mouse Protection Assay.

Ethylene interacts with abscisic acid to regulate endosperm rupture during germination: a comparative approach using Lepidium sativum and Arabidopsis thaliana.

The micropylar endosperm cap covering the radicle in the mature seeds of most angiosperms acts as a constraint that regulates seed germination. Here, we report on a comparative seed biology study with the close Brassicaceae relatives Lepidium sativum and Arabidopsis thaliana showing that ethylene biosynthesis and signaling regulate seed germination by a mechanism that requires the coordinated action of the radicle and the endosperm cap. The larger seed size of Lepidium allows direct tissue-specific biomechanical, biochemical, and transcriptome analyses.

Safety and tolerability of onabotulinumtoxinA in the treatment of facial lines: a meta-analysis of individual patient data from global clinical registration studies in 1678 participants.

Background: OnabotulinumtoxinA for the treatment of facial lines is a widely used cosmetic medical procedure and, as such, the safety and tolerability profile is of interest to health care providers and patients. Based on data from individual studies that were conducted according to regulatory guidelines to provide adequate safety and efficacy data to support product licensure (registration studies), the overall benefit:risk profile of onabotulinumtoxinA for facial lines has been favorable.

Objective: Our objective was to increase statistical power through meta-analysis to detect treatment group differences in adverse event (AE) incidence that may not have been evident in individual registration studies.

Phytochemicals: the good, the bad and the ugly?

Phytochemicals are constitutive metabolites that enable plants to overcome temporary or continuous threats integral to their environment, while also controlling essential functions of growth and reproduction. All of these roles are generally advantageous to the producing organisms but the inherent biological activity of such constituents often causes dramatic adverse consequences in other organisms that may be exposed to them. Nevertheless, such effects may be the essential indicator of desirable properties, such as therapeutic potential, especially when the mechanism of bioactivity can be delineated.

Novel insights into seed fatty acid synthesis and modification pathways from genetic diversity and quantitative trait Loci analysis of the Brassica C genome.

Natural genetic variation in fatty acid synthesis and modification pathways determine the composition of vegetable oils, which are major components of human diet and renewable products. Based on known pathways we combined diversity and genetic analysis of metabolites to infer the existence of enzymes encoded by distinct loci, and associated these with specific elongation steps or subpathways. A total of 107 lines representing different Brassica genepools revealed considerable variation for 18 seed fatty acid products.

Seed dormancy release in Arabidopsis Cvi by dry after-ripening, low temperature, nitrate and light shows common quantitative patterns of gene expression directed by environmentally specific sensing.

The depth of seed dormancy can be influenced by a number of different environmental signals, but whether a common mechanism underlies this apparently similar response has yet to be investigated. Full-genome microarrays were used for a global transcript analysis of Arabidopsis thaliana Cape Verde Island accession seeds exposed to dry after-ripening (AR), or low temperature, nitrate and light when imbibed. Germination studies showed that the sensitivity of imbibed seeds to low temperature, nitrate and light was dependent upon the length of time spent AR following harvest.

Identification and characterization of QTL controlling Agrobacterium-mediated transient and stable transformation of Brassica oleracea.

A commonly encountered difficulty with the genetic engineering of crop plants is that different varieties of a particular species can show great variability in the efficiency with which they can be transformed. This increases the effort required to introduce transgenes into particular genetic backgrounds. The use of Substitution Lines has allowed the finer mapping of three Quantitative Trait Loci (tf1, tf2 and tf3) that explain 26% of the variation in the efficiency of Agrobacterium-mediated transformation in Brassica oleracea.

Detection and resolution of genetic loci affecting circadian period in Brassica oleracea.

Circadian rhythms regulate many aspects of plant growth, fitness and vigour. The components and detailed mechanism of circadian regulation to date have been dissected in the reference species Arabidopsis thaliana. To determine the genetic basis and range of natural allelic variation for intrinsic circadian period in the closest crop relatives, we used an accurate and high throughput data capture system to record rhythmic cotyledon movement in two immortal segregating populations of Brassica oleracea, derived from parent lines representing different crop types.

Intergenerational family conversations and decision making about eating healthfully.

Objective: To explore how youth, parents, and grandparents discuss issues related to eating healthfully and unhealthfully and to identify intergenerational strategies for educators to improve this communication.

Design: In three intergenerational focus groups, each with 4-8 families, a trained moderator asked questions about family practices and conversations for eating healthfully and unhealthfully.

Setting: Three focus group sites, each with Pennsylvania Nutrition Education Program sites (PANEP) programs serving low-income populations and multigenerational clientele, based in geographically and culturally diverse communities in Pennsylvania.

FLOWERING LOCUS C-dependent and -independent regulation of the circadian clock by the autonomous and vernalization pathways.

Background: The circadian system drives pervasive biological rhythms in plants. Circadian clocks integrate endogenous timing information with environmental signals, in order to match rhythmic outputs to the local day/night cycle. Multiple signaling pathways affect the circadian system, in ways that are likely to be adaptively significant.

Comparative toxicosis of sodium selenite and selenomethionine in lambs.

Excess consumption of selenium (Se) accumulator plants can result in selenium intoxication. The objective of the study reported here was to compare the acute toxicosis caused by organic selenium (selenomethionine) found in plants with that caused by the supplemental, inorganic form of selenium (sodium selenite). Lambs were orally administered a single dose of selenium as either sodium selenite or selenomethionine and were monitored for 7 days, after which they were euthanized and necropsied.

FLOWERING LOCUS C mediates natural variation in the high-temperature response of the Arabidopsis circadian clock.

Temperature compensation contributes to the accuracy of biological timing by preventing circadian rhythms from running more quickly at high than at low temperatures. We previously identified quantitative trait loci (QTL) with temperature-specific effects on the circadian rhythm of leaf movement, including a QTL linked to the transcription factor FLOWERING LOCUS C (FLC). We have now analyzed FLC alleles in near-isogenic lines and induced mutants to eliminate other candidate genes.

Evaluation of the respiratory elimination kinetics of selenium after oral administration in sheep.

Objective: To evaluate the respiratory excretion and elimination kinetics of organic and inorganic selenium after oral administration in sheep.

Animals: 38 crossbred sheep.

Procedures: Selenium was administered PO to sheep as a single dose of 0, 1, 2, 3, or 4 mg/kg as sodium selenite or selenomethionine.