Chronic Critical Illness and Persistent Inflammation: What can we Learn from the Elderly, Injured, Septic, and Malnourished?

Patients in the intensive care unit (ICU) who develop chronic critical illness significantly stress the clinical capacity and financial resources of healthcare systems. Although vast improvements have been made in critical care management, outcomes for this ICU subset remain poor. A hallmark for patients who progress to chronic critical illness is the development of persistent inflammation and immunosuppression.

Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge.

Brown adipose tissue is a thermogenic organ that dissipates chemical energy as heat to protect animals against hypothermia and to counteract metabolic disease. However, the transcriptional mechanisms that determine the thermogenic capacity of brown adipose tissue before environmental cold are unknown. Here we show that histone deacetylase 3 (HDAC3) is required to activate brown adipose tissue enhancers to ensure thermogenic aptitude.

Rolipram Improves Outcome in a Rat Model of Infant Sepsis-Induced Cardiorenal Syndrome.

While the mortality rate associated with sepsis in children has fallen over the years, it still remains unacceptably high. The development of both acute cardiac dysfunction and acute kidney injury during severe sepsis is categorized as type 5 cardiorenal syndrome (CRS) and is poorly understood in infants. To address this lack of understanding and the need for an appropriate animal model in which to conduct relevant preclinical studies, we developed a model of infant sepsis-induced CRS in rat pups then evaluated the therapeutic potential of the phosphodiesterase (PDE) 4 inhibitor, rolipram.

Fruit quality of seedless watermelon grafted onto squash rootstocks under different production systems.

Background: The market demand for seedless watermelon has been continuously increasing because of consumer preference. Grafting is a useful tool to manage soilborne diseases in watermelon production, but the use of squash rootstocks may negatively affect watermelon fruit quality. Currently, most research has focused on seeded cultivars, while grafting effects on seedless watermelons remain largely unknown.

Obesity Modulates Inflammation and Lipid Metabolism Oocyte Gene Expression: A Single-Cell Transcriptome Perspective.

Context: It is hypothesized that obesity adversely affects the ovarian environment, which can disrupt oocyte maturation and embryonic development.

Objective: This study aimed to compare oocyte gene expression profiles and follicular fluid (FF) content from overweight/obese (OW) women and normal-weight (NW) women who were undergoing fertility treatments.

Design: Using single-cell transcriptomic analyses, we investigated oocyte gene expression using RNA sequencing.

A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium.

The human small intestinal epithelium possesses a distinct crypt-villus architecture and tissue polarity in which proliferative cells reside inside crypts while differentiated cells are localized to the villi. Indirect evidence has shown that the processes of differentiation and migration are driven in part by biochemical gradients of factors that specify the polarity of these cellular compartments; however, direct evidence for gradient-driven patterning of this in vivo architecture has been hampered by limitations of the in vitro systems available. Enteroid cultures are a powerful in vitro system; nevertheless, these spheroidal structures fail to replicate the architecture and lineage compartmentalization found in vivo, and are not easily subjected to gradients of growth factors.

Moving Toward a Unified Platform for Insulin Delivery and Sensing of Inputs Relevant to an Artificial Pancreas.

Advances in insulin pump and continuous glucose monitoring technology have primarily focused on optimizing glycemic control for people with type 1 diabetes. There remains a need to identify ways to minimize the physical burden of this technology. A unified platform with closely positioned or colocalized interstitial fluid glucose sensing and hormone delivery components is a potential solution.

Lateralized swim positions are conserved across environments for beluga (Delphinapterus leucas) mother-calf pairs.

Research with wild belugas has indicated that, during mother-calf swims, calves spend more time on their mothers' right side, which enables the calves to maintain visual contact with their mothers using their left eye. This bias may facilitate processing of social information by the right hemisphere, much like human and non-human primates and other animals. The current study explored the social laterality of the Cook Inlet, AK beluga population in comparison to a beluga population in managed care.

Biophysical characterization of functionalized titania nanoparticles and their application in dental adhesives.

Unlabelled: It is demonstrated that carboxylic acid-functionalized titanium dioxide (TiO) NPs produce significantly higher levels of reactive oxygen species (ROS) after visible light irradiation (400-800nm, 1600mW/cm) in comparison to nonfunctionalized TiO NPs. The level of ROS produced under these irradiation conditions was not capable of generating oxidatively induced DNA damage in a cell-free system for TiO concentrations of 0.5mg/L or 5mg/L.

Quantifying Disparities in Urban Firearm Violence by Race and Place in Philadelphia, Pennsylvania: A Cartographic Study.

Objectives: To describe variability in the burden of firearm violence by race, income, and place in an urban context.

Methods: We used Philadelphia Police Department data from 2013 to 2014 to calculate firearm assault rates within census block groups for both victim residence and event locations, stratifying by race and block group income. We used cartographic modeling to determine variations in incidence of firearm assault by race, neighborhood income, and place.

Automated microraft platform to identify and collect non-adherent cells successfully gene-edited with CRISPR-Cas9.

Microraft arrays have been used to screen and then isolate adherent and non-adherent cells with very high efficiency and excellent viability; however, manual screening and isolation limits the throughput and utility of the technology. In this work, novel hardware and software were developed to automate the microraft array platform. The developed analysis software identified microrafts on the array with greater than 99% sensitivity and cells on the microrafts with 100% sensitivity.

Separation, Sizing, and Quantitation of Engineered Nanoparticles in an Organism Model Using Inductively Coupled Plasma Mass Spectrometry and Image Analysis.

For environmental studies assessing uptake of orally ingested engineered nanoparticles (ENPs), a key step in ensuring accurate quantification of ingested ENPs is efficient separation of the organism from ENPs that are either nonspecifically adsorbed to the organism and/or suspended in the dispersion following exposure. Here, we measure the uptake of 30 and 60 nm gold nanoparticles (AuNPs) by the nematode, Caenorhabditis elegans, using a sucrose density gradient centrifugation protocol to remove noningested AuNPs. Both conventional inductively coupled plasma mass spectrometry (ICP-MS) and single particle (sp)ICP-MS are utilized to measure the total mass and size distribution, respectively, of ingested AuNPs.

Nicotine plus a high-fat diet triggers cardiomyocyte apoptosis.

Cigarette smoking is an important risk factor for diabetes, cardiovascular disease and non-alcoholic fatty liver disease. The health risk associated with smoking can be aggravated by obesity. Smoking might also trigger cardiomyocyte (CM) apoptosis.

Not Only Size Matters: Early-Talker and Late-Talker Vocabularies Support Different Word-Learning Biases in Babies and Networks.

In typical development, word learning goes from slow and laborious to fast and seemingly effortless. Typically developing 2-year-olds seem to intuit the whole range of things in a category from hearing a single instance named-they have word-learning biases. This is not the case for children with relatively small vocabularies (late talkers).

Identification and isolation of antigen-specific cytotoxic T lymphocytes with an automated microraft sorting system.

The simultaneous measurement of T cell function with recovery of individual T cells would greatly facilitate characterizing antigen-specific responses both in vivo and in model systems. We have developed a microraft array methodology that automatically measures the ability of individual T cells to kill a population of target cells and viably sorts specific cells into a 96-well plate for expansion. A human T cell culture was generated against the influenza M1p antigen.

Consumer Acceptability of Fresh-Market Muscadine Grapes.

The objective of this research was to investigate the acceptability of muscadine grape (Vitis rotundifolia) genotypes (cultivars and selections) and to correlate overall liking to other quality measurements to determine the main drivers of liking. Twenty-two genotypes grown at the Univ. of Georgia-Tifton Campus were evaluated.

Development of a protease-resistant reporter to quantify BCR-ABL activity in intact cells.

A peptidase-resistant ABL kinase substrate was developed by identifying protease-susceptible bonds on an ABL substrate peptide and replacing flanking amino acids with non-native amino acids. After an iterative design process, the lead, or designed, peptide X-A possesses a six-fold longer life in a cytosolic lysate than that of the starting peptide. The catalytic efficiency (k/K) of purified ABL kinase for the lead peptide (125 s μM) is similar to that of the starting peptide (103 s μM) demonstrating preservation of the peptide's ability to serve as a kinase substrate.

Emerging metrology for high-throughput nanomaterial genotoxicology.

The rapid development of the engineered nanomaterial (ENM) manufacturing industry has accelerated the incorporation of ENMs into a wide variety of consumer products across the globe. Unintentionally or not, some of these ENMs may be introduced into the environment or come into contact with humans or other organisms resulting in unexpected biological effects. It is thus prudent to have rapid and robust analytical metrology in place that can be used to critically assess and/or predict the cytotoxicity, as well as the potential genotoxicity of these ENMs.

Management of the risks for inherited disease in donor-conceived offspring.

Objective: To illustrate the burden of inherited disease on donor-conceived offspring based on mode of inheritance and to provide guidance on methods of risk reduction.

Design: An 8.5-year retrospective review of outcome reports and donor management to summarize medical risks to donor-conceived offspring that presented after the sperm donors were qualified for participation in the donor program.

Selective single cell isolation for genomics using microraft arrays.

Genomic methods are used increasingly to interrogate the individual cells that compose specific tissues. However, current methods for single cell isolation struggle to phenotypically differentiate specific cells in a heterogeneous population and rely primarily on the use of fluorescent markers. Many cellular phenotypes of interest are too complex to be measured by this approach, making it difficult to connect genotype and phenotype at the level of individual cells.

Single Cell Chemical Cytometry of Akt Activity in Rheumatoid Arthritis and Normal Fibroblast-like Synoviocytes in Response to Tumor Necrosis Factor α.

The etiology of rheumatoid arthritis (RA) is poorly understood, and 30% of patients are unresponsive to established treatments targeting tumor necrosis factor α (TNFα). Akt kinase is implicated in TNFα signaling and may act as a barometer of patient responses to biologic therapies. Fluorescent peptide sensors and chemical cytometry were employed to directly measure Akt activity as well as proteolytic activity in individual fibroblast-like synoviocytes (FLS) from RA and normal subjects.

Antioxidant Cerium Oxide Nanoparticles in Biology and Medicine.

Previously, catalytic cerium oxide nanoparticles (CNPs, nanoceria, CeO2-x NPs) have been widely utilized for chemical mechanical planarization in the semiconductor industry and for reducing harmful emissions and improving fuel combustion efficiency in the automobile industry. Researchers are now harnessing the catalytic repertoire of CNPs to develop potential new treatment modalities for both oxidative- and nitrosative-stress induced disorders and diseases. In order to reach the point where our experimental understanding of the antioxidant activity of CNPs can be translated into useful therapeutics in the clinic, it is necessary to evaluate the most current evidence that supports CNP antioxidant activity in biological systems.

A review of daycase GA services for Special Care patients at University Hospital, Bristol.

This paper describes and discusses a review of adult special care dentistry day cases in a UK hospital over a two year period and makes recommendations for other such reviews and for practice. Dental public health competencies illustrated: oral health needs assessment and evaluation of dental health services.