Colonoscopy-based colorectal cancer modeling in mice with CRISPR-Cas9 genome editing and organoid transplantation.

Most genetically engineered mouse models (GEMMs) of colorectal cancer are limited by tumor formation in the small intestine, a high tumor burden that limits metastasis, and the need to generate and cross mutant mice. Cell line or organoid transplantation models generally produce tumors in ectopic locations-such as the subcutaneous space, kidney capsule, or cecal wall-that do not reflect the native stromal environment of the colon mucosa. Here, we describe detailed protocols to rapidly and efficiently induce site-directed tumors in the distal colon of mice that are based on colonoscopy-guided mucosal injection.

Fine-tuning the normal tissue objective in eclipse for lung stereotactic body radiation therapy.

The purpose of this study was to characterize the effects of the normal tissue objective (NTO) on lung stereotactic body radiation therapy (SBRT) dose distributions. The NTO is a spatially varying constraint used in Eclipse to limit dose to normal tissues by steepening the dose gradient. However, the multitude of potential NTO setting combinations challenges optimal NTO tuning.

Association of prehospital intubation with decreased survival among pediatric trauma patients in Iraq and Afghanistan.

Introduction: Airway compromise is the second leading cause of preventable death on the battlefield among US military casualties. Airway management is an important component of pediatric trauma care. Yet, intubation is a challenging skill with which many prehospital providers have limited pediatric experience.

Corrigendum: In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis.

This corrects the article DOI: 10.1038/nbt.3836.

PKM2 is not required for colon cancer initiated by APC loss.

Background: Cancer cells express the M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2). PKM2 expression is not required for some cancers, and PKM2 loss can promote cancer progression; however, PKM2 has been reported to be essential in other tumor contexts, including a proposed non-metabolic role in β-catenin nuclear translocation. PKM2 is expressed in colon cancers where loss of the tumor suppressor results in β-catenin nuclear translocation and aberrant activation of the canonical Wnt signaling pathway.

An Inexpensive Esophageal Balloon Tamponade Trainer.

Background: Emergency medicine practitioners must be able to perform rare, life-saving procedures. One such example is esophageal balloon tamponade, which is complex, fraught with complications, and difficult to demonstrate and practice.

Discussion: We constructed a simple, inexpensive model esophagus and stomach that we attached to a mannequin, allowing emergency medicine residents to visualize and practice esophageal balloon tamponade device placement.

Square biphasic pulse deep brain stimulation for essential tremor: The BiP tremor study.

Background: Conventional deep brain stimulation (DBS) utilizes regular, high frequency pulses to treat medication-refractory symptoms in essential tremor (ET). Modifications of DBS pulse shape to achieve improved effectiveness is a promising approach.

Objectives: The current study assessed the safety, tolerability and effectiveness of square biphasic pulse shaping as an alternative to conventional ET DBS.

Gait Retraining From Rearfoot Strike to Forefoot Strike does not change Running Economy.

Gait retraining is a method for management of patellofemoral pain, which is a common ailment among recreational runners. The present study investigated the effects of gait retraining from rearfoot strike to forefoot strike on running economy, heart rate, and respiratory exchange ratio immediately post-retraining and one-month post-retraining in recreational runners with patellofemoral pain. Knee pain was also measured.

Safety evaluation of HOWARU Restore (Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-37, Bifidobacterium animalis subsp. lactis Bl-04 and B. lactis Bi-07) for antibiotic resistance, genomic risk factors, and acute toxicity.

Although probiotic lactobacilli and bifidobacteria are generally considered safe by various regulatory agencies, safety properties, such as absence of transferable antibiotic resistance, must still be determined for each strain prior to market introduction as a probiotic. Safety requirements for probiotics vary regionally and evaluation methods are not standardized, therefore methodologies are often adopted from food ingredients or chemicals to assess microbial safety. Four individual probiotic strains, Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-37, Bifidobacterium animalis subsp.

Freezing-of-Gait detection using temporal, spatial, and physiological features with a support-vector-machine classifier.

Freezing-of-Gait (FoG) is a syndrome of Parkinson's disease defined by episodes when patients show a complete inability to take a step or continue with their locomotion. In order to develop closed-loop therapeutic strategies, including deep brain stimulation, a reliable means of detecting freezing episodes is required. By using wearable accelerometers, freezing episodes can be detected with energy-based algorithms when the ratio of the energy in the freeze band (3 to 8 Hz) to that of the locomotion band (0.

Myasthenia Gravis and Crisis: Evaluation and Management in the Emergency Department.

Background: Myasthenia gravis (MG) is an uncommon autoimmune disorder affecting the neuromuscular junction and manifesting as muscle weakness. A multitude of stressors can exacerbate MG. When symptoms are exacerbated, muscle weakness can be severe enough to result in respiratory failure, a condition known as myasthenic crisis (MC).

Succeeding in New Vaccine Introduction: Lessons Learned From the Introduction of Inactivated Poliovirus Vaccine in Cameroon, Kenya, and Nigeria.

Introducing a new vaccine is a large-scale endeavor that can face many challenges, resulting in introduction delays and inefficiencies. The development of national task teams and tools, such as prelaunch trackers, for the introduction of new vaccines (hereafter, "new vaccine introductions" [NVIs]) can help countries implement robust project management systems, front-load critical preparatory activities, and ensure continuous communication around vaccine supply and financing. In addition, implementing postlaunch assessments to take rapid corrective action accelerates the uptake of the new vaccines.

Incorporation of in vitro digestive enzymes in an intestinal epithelial cell line model for protein hazard identification.

Relatively few proteins in nature produce adverse effects following oral exposure. Of those that do, effects are often observed in the gut, particularly on intestinal epithelial cells (IEC). Previous studies reported that addition of protein toxins to IEC lines disrupted monolayer integrity but innocuous dietary proteins did not.

Safety Assessment of Food and Feed from GM Crops in Europe: Evaluating EFSA's Alternative Framework for the Rat 90-day Feeding Study.

Regulatory-compliant rodent subchronic feeding studies are compulsory regardless of a hypothesis to test, according to recent EU legislation for the safety assessment of whole food/feed produced from genetically modified (GM) crops containing a single genetic transformation event (European Union Commission Implementing Regulation No. 503/2013). The Implementing Regulation refers to guidelines set forth by the European Food Safety Authority (EFSA) for the design, conduct, and analysis of rodent subchronic feeding studies.

Metabolic Teamwork in the Stem Cell Niche.

Nearby cells can support stem cell differentiation, but the metabolic activities in stem cell niches are unknown. A recent study (Rodríguez-Colman et al., 2017) reveals a metabolic partnership in the intestinal stem cell niche: glycolysis in niche Paneth cells provides lactate to drive mitochondrial oxidative phosphorylation in intestinal stem cells.

In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis.

In vivo interrogation of the function of genes implicated in tumorigenesis is limited by the need to generate and cross germline mutant mice. Here we describe approaches to model colorectal cancer (CRC) and metastasis, which rely on in situ gene editing and orthotopic organoid transplantation in mice without cancer-predisposing mutations. Autochthonous tumor formation is induced by CRISPR-Cas9-based editing of the Apc and Trp53 tumor suppressor genes in colon epithelial cells and by orthotopic transplantation of Apc-edited colon organoids.

The bear in Eurasian plant names: motivations and models.

Ethnolinguistic studies are important for understanding an ethnic group's ideas on the world, expressed in its language. Comparing corresponding aspects of such knowledge might help clarify problems of origin for certain concepts and words, e.g.

Bariatric Surgery Prior to Index Screening Colonoscopy Is Associated With a Decreased Rate of Colorectal Adenomas in Obese Individuals.

Objectives: Obesity is an important risk factor for the development of colorectal cancer (CRC). Although the impact of bariatric surgery on CRC is conflicting, its impact on precursor lesions is unknown. The aim of this study was to determine whether bariatric surgery before index screening colonoscopy is associated with decreased development of colorectal adenomas.

Mechanotransductive cascade of Myo-II-dependent mesoderm and endoderm invaginations in embryo gastrulation.

Animal development consists of a cascade of tissue differentiation and shape change. Associated mechanical signals regulate tissue differentiation. Here we demonstrate that endogenous mechanical cues also trigger biochemical pathways, generating the active morphogenetic movements shaping animal development through a mechanotransductive cascade of Myo-II medio-apical stabilization.

Split-Belt Treadmill Walking Alters Lower Extremity Frontal Plane Mechanics.

Interventions that manipulate gait speed may also affect the control of frontal plane mechanics. Expanding the current knowledge of frontal plane adaptations during split-belt treadmill walking could advance our understanding of the influence of asymmetries in gait speed on frontal plane mechanics and provide insight into the breadth of adaptations required by split-belt walking (SBW). Thirteen young, healthy participants, free from lower extremity injury walked on a split-belt treadmill with belts moving simultaneously at different speeds.

Perception of symmetry and asymmetry in individuals with anterior cruciate ligament reconstruction.

Background: Changes in the quantity, quality and integration of sensory information are thought to persist long after anterior cruciate ligament reconstruction and completion of physical therapy. Our purpose was to investigate the ability of individuals with anterior cruciate ligament reconstruction to perceive imposed asymmetry and symmetry while walking.

Methods: Twenty participants with anterior cruciate ligament reconstruction and 20 controls walked on a split-belt treadmill while we assessed the ability to detect symmetry and asymmetry at fast and slow speeds.

The Surface-Associated Exopolysaccharide of Bifidobacterium longum 35624 Plays an Essential Role in Dampening Host Proinflammatory Responses and Repressing Local TH17 Responses.

Unlabelled: The immune-modulating properties of certain bifidobacterial strains, such as Bifidobacterium longum subsp. longum 35624 (B. longum 35624), have been well described, although the strain-specific molecular characteristics associated with such immune-regulatory activity are not well defined.

Fungicide treatment and clipping of Oxytropis sericea does not disrupt swainsonine concentrations.

Swainsonine, an indolizidine alkaloid, is an α-mannosidase and mannosidase II inhibitor that causes lysosomal storage disease and alters glycoprotein processing. Swainsonine is found in a number of plant species worldwide, and is produced by associated endophytic fungi. Prolonged consumption of swainsonine-containing plants by livestock causes a condition characterized by weight loss, depression, altered behavior, decreased libido, infertility, and death.

Intraindividual Variability in Test-Retest Air Displacement Plethysmography Measurements of Body Density for Men and Women.

Air displacement plethysmography (ADP) is a popular method for estimating body density (Db). Most ADP tests are performed once, with test-retest investigations scarce. Therefore, we investigated test-retest reliability of ADP.

Genome Analysis and Characterisation of the Exopolysaccharide Produced by Bifidobacterium longum subsp. longum 35624™.

The Bifibobacterium longum subsp. longum 35624™ strain (formerly named Bifidobacterium longum subsp. infantis) is a well described probiotic with clinical efficacy in Irritable Bowel Syndrome clinical trials and induces immunoregulatory effects in mice and in humans.