Radioiodinated Capsids Facilitate In Vivo Non-Invasive Tracking of Adeno-Associated Gene Transfer Vectors.

Viral vector mediated gene therapy has become commonplace in clinical trials for a wide range of inherited disorders. Successful gene transfer depends on a number of factors, of which tissue tropism is among the most important. To date, definitive mapping of the spatial and temporal distribution of viral vectors in vivo has generally required postmortem examination of tissue.

The quality and effectiveness of interventions that target multiple risk factors among young people: a systematic review.

Objective: To identify evaluations of interventions that target multiple risk factors in high-risk young people, describe their characteristics, critique their methodological quality and summarise their effectiveness.

Methods: A search of the literature published between 2009 and 2014 identified 13 evaluations of interventions that targeted multiple risk factors, compared to 95 evaluations that targeted single risk factors. The methodological adequacy of the 13 evaluation studies was analysed using the Quality Assessment Tool for Quantitative Studies and information regarding characteristics and intervention effectiveness was extracted and summarised.

Matrix-Assisted Ionization on a Portable Mass Spectrometer: Analysis Directly from Biological and Synthetic Materials.

Matrix-assisted ionization (MAI)-mass spectrometry (MS) eliminates the need for high voltage, a heat source, lasers, and compressed gases in the ionization process and uses minimal solvents in sample preparation, thus making MAI ideal for field-portable mass spectrometers. The broad applicability of MAI is demonstrated by simple, rapid, and robust positive and negative detection mode analyses of low and high mass compounds including some pesticides, dyes, drugs, lipids, and proteins (186 Da to 8.5 kDa) from various materials including urine, biological tissue sections, paper, and plant material on a low pumping capacity, single-quadrupole mass spectrometer.

Patient-Reported Outcomes in Oncology Drug Labeling in the United States: A Framework for Navigating Early Challenges.

Background: Despite an increased use of patient-reported outcomes (PROs) in oncology clinical trials, integrating the patient perspective into drug approval decisions and documentation has been challenging.

Objectives: To review important regulatory and measurement terminology, and to provide oncology outcomes researchers and those involved with building oncology programs with tools to plan PRO data collection, particularly in relation to drug efficacy claims for drug labeling in the United States.

Discussion: When contemplating a PRO measurement strategy for oncology clinical trials, outcomes researchers are challenged in several ways.

Two-Step Route to Diverse N-Functionalized Peptidomimetic-like Isatins through an Oxidation/Intramolecular Oxidative-Amidation Cascade of Ugi Azide and Ugi Three-Component Reaction Products.

Two-step methodology described herein showcases the first example of an oxidation/oxidative amidation cyclization cascade of MCR products toward diverse N-functionalized isatins. Products of both the Ugi 3CR and the Ugi azide reactions are oxidatively cyclized through a postcondensation process utilizing selenium dioxide. This methodology was found to be applicable for the generation of bis-peptidomimetic-like isatins containing multiple points of diversification.

A synthetic review of notoedres species mites and mange.

Notoedric mange, caused by obligately parasitic sarcoptiform Notoedres mites, is associated with potentially fatal dermatitis with secondary systemic disease in small mammals, felids and procyonids among others, as well as an occasional zoonosis. We describe clinical spectra in non-chiropteran hosts, review risk factors and summarize ecological and epidemiological studies. The genus is disproportionately represented on rodents.

Myelin-targeted, texaphyrin-based multimodal imaging agent for magnetic resonance and optical imaging.

Reliable methods of imaging myelin are essential to investigate the causes of demyelination and to study drugs that promote remyelination. Myelin-specific compounds can be developed into imaging probes to detect myelin with various imaging techniques. The development of multimodal myelin-specific imaging probes enables the use of orthogonal imaging techniques to accurately visualize myelin content and validate experimental results.

Patient-Reported Outcomes in Metastatic Breast Cancer: A Review of Industry-Sponsored Clinical Trials.

Introduction: Patient-reported outcome (PRO) measures serve to capture vital patient information not otherwise obtained by primary study endpoints. This paper examines how PROs are utilized as endpoints in industry-sponsored metastatic breast cancer clinical trials.

Methods: A search was conducted in the clinicaltrials.

Investment appraisal of automatic milking and conventional milking technologies in a pasture-based dairy system.

The successful integration of automatic milking (AM) systems and grazing has resulted in AM becoming a feasible alternative to conventional milking (CM) in pasture-based systems. The objective of this study was to identify the profitability of AM in a pasture-based system, relative to CM herringbone parlors with 2 different levels of automation, across 2 farm sizes, over a 10-yr period following initial investment. The scenarios which were evaluated were (1) a medium farm milking 70 cows twice daily, with 1 AM unit, a 12-unit CM medium-specification (MS) parlor and a 12-unit CM high-specification (HS) parlor, and (2) a large farm milking 140 cows twice daily with 2 AM units, a 20-unit CM MS parlor and a 20-unit CM HS parlor.

Development of the multiple sclerosis (MS) early mobility impairment questionnaire (EMIQ).

The Early Mobility Impairment Questionnaire (EMIQ) was developed to facilitate early identification of mobility impairments in multiple sclerosis (MS) patients. We describe the initial development of the EMIQ with a focus on the psychometric evaluation of the questionnaire using classical and item response theory methods. The initial 20-item EMIQ was constructed by clinical specialists and qualitatively tested among people with MS and physicians via cognitive interviews.

Microphthalmia-associated transcription factor suppresses invasion by reducing intracellular GTP pools.

Melanoma progression is associated with increased invasion and, often, decreased levels of microphthalmia-associated transcription factor (MITF). Accordingly, downregulation of MITF induces invasion in melanoma cells; however, little is known about the underlying mechanisms. Here, we report for the first time that depletion of MITF results in elevation of intracellular GTP levels and increased amounts of active (GTP-bound) RAC1, RHO-A and RHO-C.

Can Community and School-Based Supports Improve the Achievement of First-Generation Immigrant Children Attending High-Poverty Schools?

Using a quasi-experimental design, the effects of a student support intervention were estimated for the math and reading achievement of first-generation immigrant children (n = 667, M = 11.05 years of age) attending high-poverty, urban elementary schools. The intervention was designed to help schools identify developmental strengths and barriers to learning and, in turn, connect children to community and school supports aligned with their strengths and needs.

A new minimally invasive treatment for cesarean scar pregnancy and cervical pregnancy.

Background: Cesarean scar pregnancy and cervical pregnancy are unrelated forms of pathological pregnancies carrying significant diagnostic and treatment challenges, with a wide range of treatment effectiveness and complication rates ranging from 10% to 62%. At times, life-saving hysterectomy and uterine artery embolization are required to treat complications. Based on our previous success with using a single-balloon catheter for the treatment of cesarean scar pregnancy after local injection of methotrexate, we evaluated the use of a double-balloon catheter to terminate the pregnancy while preventing bleeding without any additive treatment.

Correlates of Subjective Caregiver Strain in Caregivers of Youth Evaluated in a Pediatric Psychiatric Emergency Room.

Background: Although caregiver burden is relevant to the outcome for psychiatrically ill youth, most studies have focused on caregiver burden in the community or research settings. Therefore, we aimed at evaluating the subjective caregiver strain (SCS) at the time of presentation of youth to a pediatric psychiatric emergency room (PPER), assessing potential correlates to provide leads for improvements in formal support systems.

Methods: In this retrospective cohort study, the internalized, externalized, and total SCS were assessed in caregivers of youth <18 years of age consecutively evaluated at a PPER during a 1 year period using the Caregiver Strain Questionnaire.

Evaluating Permeability Surface-Area Product as a Measure of Blood-Brain Barrier Permeability in a Murine Model.

Background And Purpose: Permeability surface-area product has been suggested as a marker for BBB permeability with potential applications in clinical care and research. However, few studies have demonstrated its correlation with actual quantitative measurements of BBB permeability. Our aim was to demonstrate the correlation of quantitative permeability surface-area product and BBB permeability in a murine model by histologic confirmation.

Rapid high mass resolution mass spectrometry using matrix-assisted ionization.

Matrix-assisted ionization (MAI) is demonstrated to be a robust and sensitive analytical method capable of analyzing proteins such as cholera toxin B-subunit and pertussis toxin mutant from conditions containing relatively high amounts of inorganic salts, buffers, and preservatives without the need for prior sample clean-up or concentration. By circumventing some of the sample preparation steps, MAI simplifies and accelerates the analytical workflow for biological samples in complex media. The benefits of multiply charged ions characteristic of electrospray ionization (ESI) and the robustness of matrix-assisted laser desorption/ionization (MALDI) can be obtained from a single method, making it well suited for analysis of proteins and other biomolecules at ultra-high resolution as demonstrated on an Orbitrap Fusion where protein subunits were resolved for which MALDI-time-of-flight failed.

Prevalence and Treatment Outcomes of Persistent Negative Mood Among Children with Attention-Deficit/Hyperactivity Disorder and Aggressive Behavior.

Objective: Diagnostic criteria for disruptive mood dysregulation disorder (DMDD) require 1) periodic rageful outbursts and 2) disturbed mood (anger or irritability) that persists most of the time in between outbursts. Stimulant monotherapy, methodically titrated, often culminates in remission of severe aggressive behavior, but it is unclear whether those with persistent mood symptoms benefit less.This study examined the association between the presence of persistent mood disturbances and treatment outcomes among children with attention-deficit/hyperactivity disorder (ADHD) and periodic aggressive, rageful outbursts.