Epigenetic origins of metabolic disease:The impact of the maternal condition to the offspring epigenome and later health consequences

It has long been established that an adverse maternal condition impacts on the developing fetus and predisposes the offspring to develop metabolic and cardiovascular disease in later life.However,the underlying mechanisms that are initiated during development and contribute to the disease predisposition are understudied.Recently,epigenetic reprogramming in early life has emerged as a promising candidate that could cause altered DNA transcription and gene expression into adulthood and contribute to disease susceptibility.This review will focus on the impact of maternal high fat diet to the offspring in early life and the adult health consequences.We will then discuss the current literature supporting a role for epigenetic modification,such as DNA methylation and histone modifications,as a key mechanism underlying developmental programming.©2013 Beijing Academy of Food Sciences.Production and hosting by Elsevier B.V.All rights reserved.

Particle-Mediated Histotripsy for the Targeted Treatment of Intraluminal Biofilms in Catheter-Based Medical Devices

Objective.This paper is an initial work towards developing particle-mediated histotripsy(PMH)as a novel method of treating catheter-based medical device(CBMD)intraluminal biofilms.Impact Statement.CBMDs commonly become infected with bacterial biofilms leading to medical device failure,infection,and adverse patient outcomes.Introduction.Histotripsy is a noninvasive focused ultrasound ablation method that was recently proposed as a novel method to remove intraluminal biofilms.Here,we explore the potential of combining histotripsy with acoustically active particles to develop a PMH approach that can noninvasively remove biofilms without the need for high acoustic pressures or real-time image guidance for targeting.Methods.Histotripsy cavitation thresholds in catheters containing either gas-filled microbubbles(MBs)or fluid-filled nanocones(NCs)were determined.The ability of these particles to sustain cavitation over multiple ultrasound pulses was tested after a series of histotripsy exposures.Next,the ability of PMH to generate selective intraluminal cavitation without generating extraluminal cavitation was tested.Finally,the biofilm ablation and bactericidal capabilities of PMH were tested using both MBs and NCs.Results.PMH significantly reduced the histotripsy cavitation threshold,allowing for selective luminal cavitation for both MBs and NCs.Results further showed PMH successfully removed intraluminal biofilms in Tygon catheters.Finally,results from bactericidal experiments showed minimal reduction in bacteria viability.Conclusion.The results of this study demonstrate the potential for PMH to provide a new modality for removing bacterial biofilms from CBMDs and suggest that additional work is warranted to develop histotripsy and PMH for treatment of CBMD intraluminal biofilms.

TREMble Before TREM2:The Mighty Microglial Receptor Conferring Neuroprotective Properties in TDP-43 Mediated Neurodegeneration

Microglia were long hailed as solely infammatory cells,and though they are responsible for the brain's immuneresponse,they perform a variety of neuroprotective func-tions including the clearance of cellular and toxic debris^([1]).One toxic molecule known to be cleared by microglia isthe protein aggregate found in Alzheimer's Disease(AD),amyloid-B.

Targeting healthspan to optimally combat non-communicable disease in an aging world

Human lifespan and life expectancy have increased worldwide,but the number of years that we spend free of chronic or debilitating disorders,known as healthspan,has not shifted along with increased lifespan.This unfavourable trend presents a tremendous global social-economical problem.We propose a model of promoting optimal human health with proactive,holistic interventions across the lifespan,which require multi-disciplinary,innovative approaches to research and care.We contend that this is the only hope that we have to face the challenges of population growth and aging,as well as the upward trend in non-communicable disease prevalence.