Extracellular Vesicles Slow Down Aβ(1-42) Aggregation by Interfering with the Amyloid Fibril Elongation Step.

Formation of amyloid-β (Aβ) fibrils is a central pathogenic feature of Alzheimer's disease. Cell-secreted extracellular vesicles (EVs) have been suggested as disease modulators, although their exact roles and relations to Aβ pathology remain unclear. We combined kinetics assays and biophysical analyses to explore how small (<220 nm) EVs from neuronal and non-neuronal human cell lines affected the aggregation of the disease-associated Aβ variant Aβ(1-42) into amyloid fibrils.

An Extraordinary Voice Expressed Through Humor: A Tribute to Casey Quinlan.

The Journal of Participatory Medicine introduces Extraordinary Lives, a new journal section celebrating the voices and work of steadfast advocates of participatory medicine that we have lost. This inaugural essay spotlights Casey Quinlan, a patient activist who effectively used her humor and incisive analysis of health care to encourage others to strive for meaningful change. A first-generation "professional patient," Casey served as a role model who inspired many to share their stories and achieve genuine partnerships in care delivery.

Ginsenoside Rg3 Reduces the Toxicity of Graphene Oxide Used for pH-Responsive Delivery of Doxorubicin to Liver and Breast Cancer Cells.

Doxorubicin (DOX) is extensively used in chemotherapy, but it has serious side effects and is inefficient against some cancers, e.g., hepatocarcinoma.

Label-free nanofluidic scattering microscopy of size and mass of single diffusing molecules and nanoparticles.

Label-free characterization of single biomolecules aims to complement fluorescence microscopy in situations where labeling compromises data interpretation, is technically challenging or even impossible. However, existing methods require the investigated species to bind to a surface to be visible, thereby leaving a large fraction of analytes undetected. Here, we present nanofluidic scattering microscopy (NSM), which overcomes these limitations by enabling label-free, real-time imaging of single biomolecules diffusing inside a nanofluidic channel.

Chemically Synthesized, Self-Assembling Small Interfering RNA-Prohead RNA Molecules Trigger Dicer-Independent Gene Silencing.

RNA interference (RNAi) mediated by small interfering RNA (siRNA) duplexes is a powerful therapeutic modality, but the translation of siRNAs from the bench into clinical application has been hampered by inefficient delivery in vivo. An innovative delivery strategy involves fusing siRNAs to a three-way junction (3WJ) motif derived from the phi29 bacteriophage prohead RNA (pRNA). Chimeric siRNA-3WJ molecules are presumed to enter the RNAi pathway through Dicer cleavage.

High-throughput multiparametric imaging flow cytometry: toward diffraction-limited sub-cellular detection and monitoring of sub-cellular processes.

We present a sheathless, microfluidic imaging flow cytometer that incorporates stroboscopic illumination for blur-free fluorescence detection at ultra-high analytical throughput. The imaging platform is capable of multiparametric fluorescence quantification and sub-cellular localization of these structures down to 500 nm with microscopy image quality. We demonstrate the efficacy of the approach through the analysis and localization of P-bodies and stress granules in yeast and human cells using fluorescence and bright-field detection at analytical throughputs in excess of 60,000 and 400,000 cells/s, respectively.

Influence of phase of respiratory cycle on ultrasound imaging of deep abdominal muscle thickness.

Background: It is difficult to evaluate the transversus abdominis (TrA) and internal oblique (IO) due to their dual role in both trunk control and breathing.

Objectives: To investigate whether TrA and IO thickness as measured by ultrasound differs across the respiratory cycle in upright standing.

Design: Observational study.

Oscillatory Viscoelastic Microfluidics for Efficient Focusing and Separation of Nanoscale Species.

The ability to precisely control particle migration within microfluidic systems is essential for focusing, separating, counting, and detecting a wide range of biological species. To date, viscoelastic microfluidic systems have primarily been applied to the focusing, separation, and isolation of micrometer-sized species, with their use in nanoparticle manipulations being underdeveloped and underexplored, due to issues related to nanoparticle diffusivity and a need for extended channel lengths. To overcome such issues, we herein present sheathless oscillatory viscoelastic microfluidics as a method for focusing and separating both micrometer and sub-micrometer species.

Environmental Fate of RNA Interference Pesticides: Adsorption and Degradation of Double-Stranded RNA Molecules in Agricultural Soils.

Double-stranded RNA (dsRNA) pesticides are a new generation of crop protectants that interfere with protein expression in targeted pest insects by a cellular mechanism called RNA interference (RNAi). The ecological risk assessment of these emerging pesticides necessitates an understanding of the fate of dsRNA molecules in receiving environments, among which agricultural soils are most important. We herein present an experimental approach using phosphorus-32 (P)-radiolabeled dsRNA that allows studying key fate processes of dsRNA in soils with unprecedented sensitivity.

Communication at Transitions: One Audacious Bite at a Time.

To be audacious and take significant steps toward achieving the Quadruple Aim (improving the patient experience of care; improving the health of populations; reducing the per capita cost of health care; and improving the work life of clinicians and staff), we patients and caregivers need to better understand key features of our health journeys. When on that health journey, we are patients interacting with a series of care teams: our home team (social network), our community agency teams, our emergency care team, our hospital teams, and on and on. These care teams include ourselves, our caregivers, clinicians, other professionals, and direct care and support staff-people at the center of care.

Functioning Without Cartilage: Older People With Radiographic Knee Osteoarthritis Who Self-Report No Functional Limitations Do Score Lower on a Performance Battery.

The majority of the older population shows signs of radiographic knee osteoarthritis. However, many remain without functional complaints for a long period. This study aims to find early functional changes associated with stages of radiographic knee osteoarthritis.

Mosquito Rasputin interacts with chikungunya virus nsP3 and determines the infection rate in Aedes albopictus.

Background: Chikungunya virus (CHIKV) is an arthritogenic alphavirus (family Togaviridae), transmitted by Aedes species mosquitoes. CHIKV re-emerged in 2004 with multiple outbreaks worldwide and recently reached the Americas where it has infected over a million individuals in a rapidly expanding epidemic. While alphavirus replication is well understood in general, the specific function (s) of non-structural protein nsP3 remain elusive.

Effects of self-reported osteoarthritis on physical performance: a longitudinal study with a 10-year follow-up.

Background And Aims: Osteoarthritis (OA) of the knee or hip is associated with limitations in activities of daily life. There are only a few long-term studies on how knee or hip OA affects the course of physical performance. The aim of this study was to investigate the effects of knee or hip OA on physical performance during a follow-up period of 10 years.

Effect of stimulation intensity on assessment of voluntary activation.

Introduction: The interpolated twitch technique is often used to assess voluntary activation (VA) of skeletal muscles. We investigated VA and the voluntary torque-superimposed torque relationship using either supramaximal nerve stimulation or better tolerated submaximal muscle stimulation, which is often used with patients.

Methods: Thirteen healthy subjects performed maximal and submaximal isometric knee extensions with superimposed maximal or submaximal doublets (100 Hz).

Improving behavioral health satisfaction assessment: measuring patients' perceptions.

In order to focus on and improve key aspects of patient satisfaction in its behavioral health programs, Catholic Health East (CHE) enhanced its measurement methodology. In an effort to be consistent with the federal government's movement from measuring patient advocacy programs to measuring patients' perceptions, CHE transitioned to behavior-based questions. These questions give clear targets for program goals and initiatives by objectively measuring whether certain events and desired staff behaviors occurred during treatment, rather than subjectively ranking attributes of institution-defined service.

Fast unilateral isometric knee extension torque development and bilateral jump height.

Purpose: We hypothesized that the initial rate (first 40 ms) of unilateral knee extensor torque development during a maximally fast isometric contraction would depend on the subjects' ability for fast neural activation and that it would predict bilateral jumping performance.

Methods: Nine males (21.8 +/- 0.

Developing a prioritization matrix for improving breast care--a complex project.

Prioritization is an ongoing challenge for quality management professionals. A previous companion Brief Report described a tool for prioritizing improvement projects (Pelletier, Beaudin, and van Leeuwen, 1999). This tool provides a framework for prioritizing opportunities/solutions for major institutional improvement projects.