Phosphoproteomic Analyses of NRAS(G12) and NRAS(Q61) Mutant Melanocytes Reveal Increased CK2α Kinase Levels in NRAS(Q61) Mutant Cells.

In melanoma, mutant and thereby constantly active neuroblastoma rat sarcoma (NRAS) affects 15-20% of tumors, contributing to tumor initiation, growth, invasion, and metastasis. Recent therapeutic approaches aim to mimic RAS extinction by interfering with critical signaling pathways downstream of the mutant protein. This study investigates the phosphoproteome of primary human melanocytes bearing mutations in the two hot spots of NRAS, NRAS(G12) and NRAS(Q61).

Creating a hyperpolarised pseudo singlet state through polarisation transfer from parahydrogen under SABRE.

The creation of magnetic states that have long lifetimes has been the subject of intense investigation, in part because of their potential to survive the time taken to travel from the point of injection in a patient to the point where a clinically diagnostic MRI trace is collected. We show here that it is possible to harness the signal amplification by reversible exchange (SABRE) process to create such states in a hyperpolarised form that improves their detectability in seconds without the need for any chemical change by reference to the model substrate 2-aminothiazole. We achieve this by transferring Zeeman derived polarisation that is 1500 times larger than that normally available at 400 MHz with greater than 90% efficiency into the new state, which in this case has a 27 second lifetime.

Molecular MRI in the Earth's Magnetic Field Using Continuous Hyperpolarization of a Biomolecule in Water.

In this work, we illustrate a method to continuously hyperpolarize a biomolecule, nicotinamide, in water using parahydrogen and signal amplification by reversible exchange (SABRE). Building on the preparation procedure described recently by Truong et al. [ J.

Barriers and Facilitators to Adoption of Genomic Services for Colorectal Care within the Veterans Health Administration.

We examined facilitators and barriers to adoption of genomic services for colorectal care, one of the first genomic medicine applications, within the Veterans Health Administration to shed light on areas for practice change. We conducted semi-structured interviews with 58 clinicians to understand use of the following genomic services for colorectal care: family health history documentation, molecular and genetic testing, and genetic counseling. Data collection and analysis were informed by two conceptual frameworks, the Greenhalgh Diffusion of Innovation and Andersen Behavioral Model, to allow for concurrent examination of both access and innovation factors.

ACEMg Diet Supplement Modifies Progression of Hereditary Deafness.

Dietary supplements consisting of beta-carotene (precursor to vitamin A), vitamins C and E and the mineral magnesium (ACEMg) can be beneficial for reducing hearing loss due to aminoglycosides and overstimulation. This regimen also slowed progression of deafness for a boy with GJB2 (CONNEXIN 26) mutations. To assess the potential for treating GJB2 and other forms of hereditary hearing loss with ACEMg, we tested the influence of ACEMg on the cochlea and hearing of mouse models for two human mutations: GJB2, the leading cause of childhood deafness, and DIAPH3, a cause of auditory neuropathy.

Improved Method to Stratify Elderly Patients With Cancer at Risk for Competing Events.

Purpose: To compare a novel generalized competing event (GCE) model versus the standard Cox proportional hazards regression model for stratifying elderly patients with cancer who are at risk for competing events.

Methods: We identified 84,319 patients with nonmetastatic prostate, head and neck, and breast cancers from the SEER-Medicare database. Using demographic, tumor, and clinical characteristics, we trained risk scores on the basis of GCE versus Cox models for cancer-specific mortality and all-cause mortality.

Developing and Implementing Major League Baseball's Health and Injury Tracking System.

In 2010, Major League Baseball and the Major League Baseball Players Association reached an agreement regarding the development and implementation of an electronic medical record system and a new league-wide injury surveillance system. The systems were developed to create a more efficient method to track medical histories of players longitudinally as they move across Major and Minor league affiliates, as well as to identify and monitor injury trends in the sport, identify areas of specific concern, and conduct epidemiologic research to better optimize player health and safety. The resulting injury surveillance system, the Health and Injury Tracking System (HITS), is a robust system that includes all players from the both the Major and Minor Leagues.

Duplication 2p25 in a child with clinical features of CHARGE syndrome.

CHARGE syndrome is a dominant disorder characterized by ocular colobomata, heart defects, choanal atresia, retardation of growth and development, genital hypoplasia, and ear abnormalities including deafness and vestibular disorders. The majority of individuals with CHARGE have pathogenic variants in the gene encoding CHD7, a chromatin remodeling protein. Here, we present a 15-year-old girl with clinical features of CHARGE syndrome and a de novo 6.

The epidemiology of failure in total knee arthroplasty: avoiding your next revision.

Total knee arthroplasty (TKA) is a cost effective and extremely successful operation. As longevity increases, the demand for primary TKA will continue to rise. The success and survivorship of TKAs are dependent on the demographics of the patient, surgical technique and implant-related factors.

Setting, Structure, and Timing of the Preparticipation Examination: The Wilderness Adventure Consultation.

Patients pursue wilderness experiences throughout the entire life cycle, and while outdoor pursuits are relatively safe, injuries do occur. Many of these adverse events can be anticipated, identified, and prevented through a wilderness preparticipation examination (PPE). To accomplish this, it is incumbent on the physician to assess the extrinsic and intrinsic factors faced by the patient and attempt to correct them to ensure an enjoyable experience in the outdoors.

Atypical phenotypes associated with pathogenic CHD7 variants and a proposal for broadening CHARGE syndrome clinical diagnostic criteria.

CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital and/or urinary anomalies, and Ear malformations, including deafness and vestibular disorders) is a genetic condition characterized by a specific and recognizable pattern of features. Heterozygous pathogenic variants in the chromodomain helicase DNA-binding protein 7 (CHD7) are the major cause of CHARGE syndrome, and have been identified in 70-90% of individuals fulfilling clinical diagnostic criteria. Since 2004, when CHD7 was discovered as the causative gene for CHARGE syndrome, the phenotypic spectrum associated with pathogenic CHD7 variants has expanded.

MEG Adaptation Resolves the Spatiotemporal Characteristics of Face-Sensitive Brain Responses.

Unlabelled: An unresolved goal in face perception is to identify brain areas involved in face processing and simultaneously understand the timing of their involvement. Currently, high spatial resolution imaging techniques identify the fusiform gyrus as subserving processing of invariant face features relating to identity. High temporal resolution imaging techniques localize an early latency evoked component-the N/M170-as having a major generator in the fusiform region; however, this evoked component is not believed to be associated with the processing of identity.

Antenatal Three-Dimensional Printing of Aberrant Facial Anatomy.

Congenital airway obstruction poses a life-threatening challenge to the newborn. We present the first case of three-dimensional (3D) modeling and 3D printing of complex fetal maxillofacial anatomy after prenatal ultrasound indicated potential upper airway obstruction from a midline mass of the maxilla. Using fetal MRI and patient-specific computer-aided modeling, the craniofacial anatomy of the fetus was manufactured using a 3D printer.

Setting, Structure, and Timing of the Preparticipation Examination: The Wilderness Adventure Consultation.

Patients pursue wilderness experiences throughout the entire life cycle, and while outdoor pursuits are relatively safe, injuries do occur. Many of these adverse events can be anticipated, identified, and prevented through a wilderness preparticipation examination (PPE). To accomplish this, it is incumbent on the physician to assess the extrinsic and intrinsic factors faced by the patient and attempt to correct them to ensure an enjoyable experience in the outdoors.

Evaluating the Quality of Behavior Analytic Practitioner Training Programs.

Dixon and colleagues (2015) asserted that faculty research productivity is a key indicator of the quality of university programs that train future practitioners of behavior analysis. Based on their analysis of publications in select journals, the authors concluded that many faculty in such programs have published little to no research. Some alternative measures of both faculty research productivity and the quality of practitioner training programs are suggested here.

Regulatory Considerations in the Design and Manufacturing of Implantable 3D-Printed Medical Devices.

Three-dimensional (3D) printing, or additive manufacturing, technology has rapidly penetrated the medical device industry over the past several years, and innovative groups have harnessed it to create devices with unique composition, structure, and customizability. These distinctive capabilities afforded by 3D printing have introduced new regulatory challenges. The customizability of 3D-printed devices introduces new complexities when drafting a design control model for FDA consideration of market approval.

Investigating pyridazine and phthalazine exchange in a series of iridium complexes in order to define their role in the catalytic transfer of magnetisation from -hydrogen.

The reaction of [Ir(IMes)(COD)Cl], [IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene, COD = 1,5-cyclooctadiene] with pyridazine (pdz) and phthalazine (phth) results in the formation of [Ir(COD)(IMes)(pdz)]Cl and [Ir(COD)(IMes)(phth)]Cl. These two complexes are shown by nuclear magnetic resonance (NMR) studies to undergo a haptotropic shift which interchanges pairs of protons within the bound ligands. When these complexes are exposed to hydrogen, they react to form [Ir(H)(COD)(IMes)(pdz)]Cl and [Ir(H)(COD)(IMes)(phth)]Cl, respectively, which ultimately convert to [Ir(H)(IMes)(pdz)]Cl and [Ir(H)(IMes)(phth)]Cl, as the COD is hydrogenated to form cyclooctane.

Catalytic Transfer of Magnetism using a Neutral Iridium Phenoxide Complex.

A novel neutral iridium carbene complex Ir(κC,O-L)(COD) () [where COD = cyclooctadiene and L = 3-(2-methylene-4-nitrophenolate)-1-(2,4,6-trimethylphenyl) imidazolylidene] with a pendant alkoxide ligand has been prepared and characterized. It contains a strong Ir-O bond and X-ray analysis reveals a distorted square planar structure. NMR spectroscopy reveals dynamic solution state behavior commensurate with rapid seven-membered ring flipping.

Healthy cities as catalysts for caring and supportive environments.

'Caring and Supportive Environments' are fundamental to a social model of health and were a core theme of Phase V (2009-13) of the WHO European Healthy Cities Network. Deploying the methodology of realist evaluation, this article synthesizes qualitative evidence from 112 highly structured case studies from 68 Network cities and 71 responses to a General Evaluation Questionnaire, which asked cities to analyze city attributes and trends. A schematic model was developed to describe the interaction between action targeted toward children, migrants, older people and action on social and health services, health literacy and active citizenship-the six subtopics clustered within the theme Caring and Supportive Environments.

European Healthy Cities evaluation: conceptual framework and methodology.

This paper presents the methodology, programme logic and conceptual framework that drove the evaluation of the Fifth Phase of the WHO European Healthy Cities Network. Towards the end of the phase, 99 cities were designated progressively through the life of the phase (2009-14). The paper establishes the values, systems and aspirations that these cities sign up for, as foundations for the selection of methodology.