Reverse engineering of Onivyde® - Irinotecan liposome injection.

Onivyde® is an intravenous irinotecan liposomal injection approved by the FDA for the treatment of gemcitabine-refractory metastatic adenocarcinoma of the pancreas in combination with fluorouracil and leucovorin. In the Onivyde® formulation, irinotecan is encapsulated in the inner compartment of the liposome using sucrose octasulfate as a trapping agent, and stabilized by a pegylated lipid membrane, resulting in prolonged circulation in the body. Due to its complex formulation design, there is limited information available regarding the critical quality attributes (CQAs) of Onivyde® and suitable methods for evaluating these attributes.

Processed Food as a Risk Factor for the Development and Perpetuation of Crohn's Disease-The ENIGMA Study.

(1) Background: Developing countries have experienced a rapid recent rise in Inflammatory Bowel Disease (IBD) incidence and emerging evidence suggests processed foods and food additives may predispose one to the development and perpetuation of Crohn's disease (CD). The aim of this study was to evaluate processed food and food additive intake in CD patients and controls, in Australia (high CD incidence), Hong Kong (intermediate incidence) and mainland China (emerging incidence). (2) Methods: In 274 CD patients (CD), 82 first-degree relatives (FDR), 83 household members (HM) and 92 healthy unrelated controls (HC) from Australia (n = 180), Hong Kong (HK) (n = 160) and mainland China (n = 191) we estimated early life (0-18 years), recent (12 months), and current processed and food additive intake, using validated questionnaires and a 3-day-food diary.

Childhood antibiotics as a risk factor for Crohn's disease: The ENIGMA International Cohort Study.

Background And Aim: Environmental factors play a key role in development of Crohn's disease (CD), thought to be mediated by changes in the gut microbiota. We aimed to delineate the potential contribution of antibiotic exposure to subsequent development of CD, across diverse geographical populations.

Methods: This case-control study in Australia and three cities in China (Hong Kong, Guangzhou, and Kunming) included four groups: patients with CD, at-risk individuals including non-affected first-degree relatives (FDRs) and household members of CD patients (HM), and unrelated healthy controls (HCs).

OzTracs: Optical Osmolality Reporters Engineered from Mechanosensitive Ion Channels.

Interactions between physical forces and membrane proteins underpin many forms of environmental sensation and acclimation. Microbes survive osmotic stresses with the help of mechanically gated ion channels and osmolyte transporters. Plant mechanosensitive ion channels have been shown to function in defense signaling.

Cell-Selective Adeno-Associated Virus-Mediated Gene Regulation Therapy Rescues Mortality and Seizure Phenotypes in a Dravet Syndrome Mouse Model and Is Well Tolerated in Nonhuman Primates.

Dravet syndrome (DS) is a developmental and epileptic encephalopathy caused by monoallelic loss-of-function variants in the gene. encodes for the alpha subunit of the voltage-gated type I sodium channel (Na1.1), the primary voltage-gated sodium channel responsible for generation of action potentials in GABAergic inhibitory interneurons.

Review article: Probiotics, prebiotics and dietary approaches during COVID-19 pandemic.

Background: Patients with COVID-19 caused by SARS-CoV-2 exhibit diverse clinical manifestations and severity including enteric involvement. Commensal gut bacteria can contribute to defense against potential pathogens by promoting beneficial immune interactions. Interventions targeting the gut microbiome may have systemic anti-viral effects in SARS-CoV-2 infection.

Development and Validation of Surveys to Estimate Food Additive Intake.

(1) Background: The Food Agricultural Organization/World Health Organization (FAO/WHO) International Food Standards (hereafter, CODEX) declares additives non-toxic, but they have been associated with changes to the microbiota changes and thinning of the mucus layer of the gut. Their widespread use has occurred in parallel with increased inflammatory bowel disease (IBD) incidence. This paper reports on the development and validation of surveys to estimate additive intake.

Quality Improvement Initiative to Improve Abuse Screening Among Infants With Extremity Fractures.

Objectives: The aim of this study was to evaluate the effectiveness of clinical pathway implementation and quality improvement (QI) interventions to increase the percentage of infants with extremity fractures undergoing evaluation for suspected physical abuse, including skeletal survey (SS), and consultation with social work, and/or Child Protection Team.

Methods: Charts were retrospectively reviewed to establish percentage of infants less than 12 months old with extremity fractures undergoing an SS and consultation during the prepathway (January 1, 2012 to December 31, 2013) and postpathway (January 1, 2014 to June 30, 2015) periods. Using an Ishikawa framework, key process drivers were identified and additional QI interventions (clinical decision support and provider education) were developed and implemented.

Real-Time Interactive Tree Animation.

We present a novel method for posing and animating botanical tree models interactively in real time. Unlike other state of the art methods which tend to produce trees that are overly flexible, bending and deforming as if they were underwater plants, our approach allows for arbitrarily high stiffness while still maintaining real-time frame rates without spurious artifacts, even on quite large trees with over ten thousand branches. This is accomplished by using an articulated rigid body model with as-stiff-as-desired rotational springs in conjunction with our newly proposed simulation technique, which is motivated both by position based dynamics and the typical algorithms for articulated rigid bodies.

Sweet potato NAC transcription factor, IbNAC1, upregulates sporamin gene expression by binding the SWRE motif against mechanical wounding and herbivore attack.

Sporamin is a tuberous storage protein with trypsin inhibitory activity in sweet potato (Ipomoea batatas Lam.), which accounts for 85% of the soluble protein in tubers. It is constitutively expressed in tuberous roots but is expressed in leaves only after wounding.

A cascade of sequentially expressed sucrose transporters in the seed coat and endosperm provides nutrition for the Arabidopsis embryo.

Developing plant embryos depend on nutrition from maternal tissues via the seed coat and endosperm, but the mechanisms that supply nutrients to plant embryos have remained elusive. Sucrose, the major transport form of carbohydrate in plants, is delivered via the phloem to the maternal seed coat and then secreted from the seed coat to feed the embryo. Here, we show that seed filling in Arabidopsis thaliana requires the three sucrose transporters SWEET11, 12, and 15.

Nectar secretion requires sucrose phosphate synthases and the sugar transporter SWEET9.

Angiosperms developed floral nectaries that reward pollinating insects. Although nectar function and composition have been characterized, the mechanism of nectar secretion has remained unclear. Here we identify SWEET9 as a nectary-specific sugar transporter in three eudicot species: Arabidopsis thaliana, Brassica rapa (extrastaminal nectaries) and Nicotiana attenuata (gynoecial nectaries).

Release of retinal growth hormone in the chick embryo: local regulation?

The neural retina is an extrapituitary site of growth hormone (GH) production and an autocrine or paracrine site of retinal GH action. Retinal GH is released from retinal tissue and may be secreted into the vitreous. Ontogenetic changes in the abundance of retinal GH during embryogenesis indicate that the amount of GH released may be regulated.