Targeted delivery of TGF-β mRNA to lung parenchyma using one-component ionizable amphiphilic Janus Dendrimers.

Current clinical strategies for the delivery of pulmonary therapeutics to the lung are primarily targeted to the upper portions of the airways. However, targeted delivery to the lower regions of the lung is necessary for the treatment of parenchymal lung injury and disease. Here, we have developed an mRNA therapeutic for the lower lung using one-component Ionizable Amphiphilic Janus Dendrimers (IAJDs) as a delivery vehicle.

Dynamic diagnosis of metamaterials through laser-induced vibrational signatures.

Mechanical metamaterials at the microscale exhibit exotic static properties owing to their engineered building blocks, but their dynamic properties have remained substantially less explored. Their design principles can target frequency-dependent properties and resilience under high-strain-rate deformation, making them versatile materials for applications in lightweight impact resistance, acoustic waveguiding or vibration damping. However, accessing dynamic properties at small scales has remained a challenge owing to low-throughput and destructive characterization or lack of existing testing protocols.

Differential effects of healthcare worker burnout on psychotropic medication use and misuse by occupational level.

Purpose: Burnout has been well examined among physicians and other high-wage, high-autonomy healthcare positions. However, lower-wage healthcare workers with less workplace autonomy (e.g.

Tunable Mechanical Response of Self-Assembled Nanoparticle Superlattices.

Self-assembled nanoparticle superlattices (NPSLs) are an emergent class of self-architected nanocomposite materials that possess promising properties arising from precise nanoparticle ordering. Their multiple coupled properties make them desirable as functional components in devices where mechanical robustness is critical. However, questions remain about NPSL mechanical properties and how shaping them affects their mechanical response.

Suppression of Lung Oxidative Stress, Inflammation, and Fibrosis following Nitrogen Mustard Exposure by the Selective Farnesoid X Receptor Agonist Obeticholic Acid.

Nitrogen mustard (NM) is a cytotoxic vesicant known to cause pulmonary injury that can progress to fibrosis. NM toxicity is associated with an influx of inflammatory macrophages in the lung. Farnesoid X receptor (FXR) is a nuclear receptor involved in bile acid and lipid homeostasis that has anti-inflammatory activity.

Growth rules for irregular architected materials with programmable properties.

Biomaterials display microstructures that are geometrically irregular and functionally efficient. Understanding the role of irregularity in determining material properties offers a new path to engineer materials with superior functionalities, such as imperfection insensitivity, enhanced impact absorption, and stress redirection. We uncover fundamental, probabilistic structure-property relationships using a growth-inspired program that evokes the formation of stochastic architectures in natural systems.

Promoting simulation-based training in radiology: a homemade phantom for the practice of ultrasound-guided procedures.

Objective: Ultrasound-guided intervention is an essential skill for many radiologists and critical for accurate diagnosis and treatment in many radiology subspecialties. Simulation using phantoms have demonstrated statistically significant benefits for trainees within the literature. We propose a novel phantom model which the authors feel is ideal for training clinical radiology trainees in the performance of ultrasound-guided procedures.

Effectiveness of percutaneous vacuum-assisted excision (VAE) of breast lesions of uncertain malignant potential (B3 lesions) as an alternative to open surgical biopsy.

Objectives: Traditionally B3 breast lesions are treated surgically, but overtreatment is a concern, as the majority have a final benign diagnosis. A national screening program introduced vacuum-assisted excision (VAE) for managing B3 lesions in late 2016. This retrospective study aimed to assess the outcomes associated with this approach.

Recommendations for the content and management of Certificates of Analysis for reference standards from the GCC for bioanalysis.

The 13th Global CRO Council (GCC) closed forum for bioanalysis was held in New Orleans, LA, USA on 5 April 2019. This GCC meeting was organized to discuss the contents of the 2019 ICH M10 Bioanalytical Method Validation Draft Guideline published in February 2019 and consolidate the feedback of the GCC members. While ICH M10 will cover requirements for reference standards, one of the biggest challenges facing the CRO community is the lack of consistency and completeness of Certificates of Analysis for reference standards used in regulated bioanalysis.

Combined Intranasal Nanoemulsion and RIG-I Activating RNA Adjuvants Enhance Mucosal, Humoral, and Cellular Immunity to Influenza Virus.

Current influenza virus vaccines are focused on humoral immunity and are limited by the short duration of protection, narrow cross-strain efficacy, and suboptimal immunogenicity. Here, we combined two chemically and biologically distinct adjuvants, an oil-in-water nanoemulsion (NE) and RNA-based agonists of RIG-I, to determine whether the diverse mechanisms of these adjuvants could lead to improved immunogenicity and breadth of protection against the influenza virus. NE activates TLRs, stimulates immunogenic apoptosis, and enhances cellular antigen uptake, leading to a balanced T1/T2/T17 response when administered intranasally.

Targeting interferon signaling and CTLA-4 enhance the therapeutic efficacy of anti-PD-1 immunotherapy in preclinical model of HPV oral cancer.

Background: The US is experiencing an epidemic of HPV oropharyngeal cancers (OPC), the rates and burden of which now exceed that for cervical cancer. Immunotherapy targeting programmed death 1 (PD-1) on tumor-infiltrating lymphocytes and/or its ligand PD-L1 on tumor cells, which was effective in several cancers has however, showed efficacy in only less than 15% of patients.

Methods: We used a preclinical HPV oral tumor model, mEER, consisting of mouse tonsil derived epithelial cells expressing HPV-16 E6 and E7 genes, along with the H-ras oncogene to test strategies for enhancing the efficacy of anti-PD-1 therapy.

Steric Inhibition of 5' UTR Regulatory Elements Results in Upregulation of Human CFTR.

Cystic fibrosis (CF) is an autosomal recessive monogenic disease caused by mutations in the CFTR gene. Therapeutic approaches that are focused on correcting CFTR protein face the challenge of the heterogeneity in CFTR mutations and resulting defects. Thus, while several small molecules directed at CFTR show benefit in the clinic for subsets of CF patients, these drugs cannot treat all CF patients.

Photocontrolled Release of Doxorubicin Conjugated through a Thioacetal Photocage in Folate-Targeted Nanodelivery Systems.

Despite their proven ability for precise and targeted release, nanoplatform systems for photocontrolled delivery often face formidable synthetic challenges, in part due to the paucity of advanced linker strategies. Here, we report on a novel linker strategy using a thioacetal ortho-nitrobenzaldehyde (TNB) cage, demonstrating its application for delivery of doxorubicin (Dox) in two nanoscale systems. This photocleavable linker, TNB(OH), which presents two identical arms, each terminated with a hydroxyl functionality, was prepared in a single step from 6-nitroveratraldehyde.

2016 White Paper on recent issues in bioanalysis: focus on biomarker assay validation (BAV) (Part 1 - small molecules, peptides and small molecule biomarkers by LCMS).

The 2016 10 Workshop on Recent Issues in Bioanalysis (10 WRIB) took place in Orlando, Florida with participation of close to 700 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - A Full Immersion Week of Bioanalysis including Biomarkers and Immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecule analysis involving LCMS, hybrid LBA/LCMS, and LBA approaches, with the focus on biomarkers and immunogenicity.

Light-controlled active release of photocaged ciprofloxacin for lipopolysaccharide-targeted drug delivery using dendrimer conjugates.

We report an active delivery mechanism targeted specifically to Gram(-) bacteria based on the photochemical release of photocaged ciprofloxacin carried by a cell wall-targeted dendrimer nanoconjugate.

Positive youth development programs for adolescents with greater psychosocial needs: subjective outcome evaluation over 3 years.

Study Objectives: This study examined the views of 153,761 students participating in a positive youth development program designed for participants with greater psychosocial needs (the Tier 2 Program) in the context of the Project P.A.T.

Development of a credit-bearing service leadership subject for university students in Hong Kong.

Given that service industries contribute to 93% of Hong Kong's GDP, an important question that should be asked is whether the education system can promote the development of service leadership among young people in Hong Kong. Unfortunately, service leadership programs specifically designed for university students are lacking in Hong Kong. In this paper, the basic tenets of the Service Leadership and Management framework are presented.

Transforming potential program implementers in professional development: the Project P.A.T.H.S. in Hong Kong.

High quality pre-implementation professional training is the cornerstone for successful implementation of positive youth development programs. A qualitative evaluation study was conducted to understand the experiences of the potential program implementers of the Project P.A.

Evaluation of Project P.A.T.H.S. by the program implementers: findings based on the extension phase.

A total of 236 schools participated in the Project P.A.T.

Helping adolescents with greater psychosocial needs: the extension phase of the Project P.A.T.H.S. in Hong Kong.

Subjective outcome evaluation data were collected from 24,198 students of 236 schools after completion of the Tier 2 Program in the second year of the Extension Phase of the Project P.A.T.

Evaluation of the Project P.A.T.H.S. (extension phase) based on the perspective of the program participants.

Subjective outcome evaluation data were collected from 236 schools (n=87,943 students) after students had participated in the Tier 1 Program in the second year of the Extension Phase of the Project P.A.T.