Functional characterization of QT interval associated SCN5A enhancer variants identify combined additive effects.

Several empirical and theoretical studies suggest the presence of multiple enhancers per gene that collectively regulate gene expression, and that common sequence variation impacting on the activities of these enhancers is a major source of inter-individual gene expression variability. However, for the vast majority of genes, enhancers and the underlying regulatory variation remains unknown. Even for the genes with well-characterized enhancers, the nature of the combined effects from multiple enhancers and their variants, when known, on gene expression regulation remains unexplored.

EpicTope: narrating protein sequence features to identify non-disruptive epitope tagging sites.

Epitope tagging is an invaluable technique enabling the identification, tracking, and purification of proteins in vivo. We developed a tool, EpicTope, to facilitate this method by identifying amino acid positions suitable for epitope insertion. Our method uses a scoring function that considers multiple protein sequence and structural features to determine locations least disruptive to the protein's function.

Functional characterization of QT interval associated enhancer variants identify combined additive effects.

Several empirical and theoretical studies suggest presence of multiple enhancers per gene that collectively regulate gene expression, and that common sequence variation impacting on the activities of these enhancers is a major source of inter-individual variability in gene expression. However, for vast majority of genes, enhancers and the underlying regulatory variation remains unknown. Even for the genes with well-characterized enhancers, the nature of the combined effects from multiple enhancers and their variants, when known, on gene expression regulation remains unexplored.

Computational Modeling of Ophthalmic Procedures: Computational Modeling of Ophthalmic Procedures.

Purpose: To explore how finite-element calculations can continue to contribute to diverse problems in ophthalmology and vision science, we describe our recent work on modeling the force on the peripheral retina in intravitreal injections and how that force increases with shorter, smaller gauge needles. We also present a calculation that determines the location and stress on a retinal pigment epithelial detachment during an intravitreal injection, the possibility that stress induced by the injection can lead to a tear of the retinal pigment epithelium.

Background: Advanced computational models can provide a critical insight into the underlying physics in many surgical procedures, which may not be intuitive.

Trends in Waste Production at a Community Hospital during the COVID-19 Pandemic.

Introduction: As of September 2021, the COVID-19 pandemic has led to 42,500,000 cases and 680,000 deaths in the United States. In Rhode Island, there have been 170,000 cases and 2,820 deaths. Investigating resource utilization and waste production during disease outbreaks can inform efforts at disaster preparedness.

Dietary prebiotics alter novel microbial dependent fecal metabolites that improve sleep.

Dietary prebiotics produce favorable changes in the commensal gut microbiome and reduce host vulnerability to stress-induced disruptions in complex behaviors such as sleep. The mechanisms for how prebiotics modulate stress physiology remain unclear; however, emerging evidence suggests that gut microbes and their metabolites may play a role. This study tested if stress and/or dietary prebiotics (Test diet) alter the fecal metabolome; and explored if these changes were related to sleep and/or gut microbial alpha diversity.

Evaluation of Dietary Bovine Milk Fat Globule Membrane Supplementation on Growth, Serum Cholesterol and Lipoproteins, and Neurodevelopment in the Young Pig.

Milk fat globule membrane (MFGM) is a protein- and phospholipid-rich membrane that surrounds the lipid droplet in milk. We have previously reported that a diet composed of a combination of prebiotics, bovine MFGM (bMFGM), and lactoferrin (bLf) supported brain development in young pigs. Due to the growing interest of its potential benefits in neurodevelopment, the present study focused on the effects of dietary bMFGM alone using the pig as a translational model.

It is all in the bag: collodion bag versus HistoGel cell block method.

Introduction: We performed a comparison of cell blocks prepared with the collodion bag and HistoGel to evaluate the ease of embedding and cutting, performance with low cellularity specimens, time and cost per specimen, and value to support immunohistochemistry and molecular diagnostics.

Materials And Methods: We processed 11 fresh, unfixed effusions using both the collodion bag and the HistoGel cell block preparation methods. Six immunohistochemistry stains were tested on 2 of the body fluids.

Dietary Oligosaccharides Attenuate Stress-Induced Disruptions in Immune Reactivity and Microbial B-Vitamin Metabolism.

Exposure to stressful stimuli dysregulates inflammatory processes and alters the gut microbiota. Prebiotics, including long-chain fermentable fibers and milk oligosaccharides, have the potential to limit inflammation through modulation of the gut microbiota. To determine whether prebiotics attenuate stress-induced inflammation and microbiota perturbations, mice were fed either a control diet or a diet supplemented with galactooligosaccharides, polydextrose and sialyllactose (GOS+PDX+SL) or sialyllactose (SL) for 2 weeks prior to and during a 6-day exposure to a social disruption stressor.

The enduring effects of early-life stress on the microbiota-gut-brain axis are buffered by dietary supplementation with milk fat globule membrane and a prebiotic blend.

Nutritional interventions targeting the microbiota-gut-brain axis are proposed to modulate stress-induced dysfunction of physiological processes and brain development. Maternal separation (MS) in rats induces long-term alterations to behaviour, pain responses, gut microbiome and brain neurochemistry. In this study, the effects of dietary interventions (milk fat globule membrane [MFGM] and a polydextrose/galacto-oligosaccharide prebiotic blend) were evaluated.

Evaluation of Sialyllactose Supplementation of a Prebiotic-Containing Formula on Growth, Intestinal Development, and Bacterial Colonization in the Neonatal Piglet.

Background: Sialyllactose (SL) is a highly abundant oligosaccharide in human milk that has been shown to influence intestinal maturation and cognitive development and exert bifidogenic effects on the gut microbiota. The SL content of infant formula is significantly less than that of human milk, therefore there is interest in determining the effect of supplementing SL to infant formula at the levels in human milk on neonatal outcomes.

Objective: The aim of this study was to investigate the effect of varying doses of dietary SL compared with a milk replacer formula on weight gain, gastrointestinal development, and microbiota composition in piglets.

Dermoscopy findings of a one mm lentigo maligna.

A 66-year-old man presented with a grayish 1mm macule on the left cheek. Dermatoscopic examination revealed annular-granular structures partially surrounding a single follicular ostium. Histopathologic examination demonstrated atypical, confluent single melanocytes at the basal layer with nesting, crowding, and upward migration descending along the hair follicle, consistent with the diagnosis of lentigo maligna (LM).

Metabolomic signatures distinguish the impact of formula carbohydrates on disease outcome in a preterm piglet model of NEC.

Background: Major risk factors for necrotizing enterocolitis (NEC) include premature birth and formula feeding in the context of microbial colonization of the gastrointestinal tract. We previously showed that feeding formula composed of lactose vs. corn syrup solids protects against NEC in preterm pigs; however, the microbial and metabolic effects of these different carbohydrates used in infant formula has not been explored.

Dietary Sialyllactose Does Not Influence Measures of Recognition Memory or Diurnal Activity in the Young Pig.

Sialic acid (SA) is an integral component of gangliosides and signaling molecules in the brain and its dietary intake may support cognitive development. We previously reported that feeding sialyllactose, a milk oligosaccharide that contains SA, alters SA content and diffusivity in the pig brain. The present research sought to expand upon such results and describe the effects of feeding sialyllactose on recognition memory and sleep/wake activity using a translational pig model.

Feeding the developing brain: Juvenile rats fed diet rich in prebiotics and bioactive milk fractions exhibit reduced anxiety-related behavior and modified gene expression in emotion circuits.

Early life nutrition is critical for brain development. Dietary prebiotics and bioactive milk fractions support brain development by increasing plasticity and altering activity in brain regions important for cognition and emotion regulation, perhaps through the gut-microbiome-brain axis. Here we examined the impact of a diet containing prebiotics, lactoferrin, and milk fat globule membrane (test diet) on beneficial gut bacteria, basal gene expression for activity and plasticity markers within brain circuits important for cognition and anxiety, and anxiety-related behavior in the open field.

Dietary polydextrose and galactooligosaccharide increase exploratory behavior, improve recognition memory, and alter neurochemistry in the young pig.

Objectives: Previous studies have shown that dietary prebiotics have the potential to improve memory, alter social behavior, and reduce anxiety-like behaviors in rodents. The present research sought to expand upon such results and describe the effects of feeding prebiotics early in life on cognition and neurochemistry using a translational piglet model.

Methods: Pigs were provided customized milk replacer containing 2 g/L each of polydextrose (PDX) and galactooligosaccharide (PDX/GOS) or 0 g/L (Control) from postnatal day (PND) 2-33.

Dietary Sialyllactose Influences Sialic Acid Concentrations in the Prefrontal Cortex and Magnetic Resonance Imaging Measures in Corpus Callosum of Young Pigs.

Sialic acid (SA) is a key component of gangliosides and neural cell adhesion molecules important during neurodevelopment. Human milk contains SA in the form of sialyllactose (SL) an abundant oligosaccharide. To better understand the potential role of dietary SL on neurodevelopment, the effects of varying doses of dietary SL on brain SA content and neuroimaging markers of development were assessed in a newborn piglet model.

Neurobehavioural effects of Lactobacillus rhamnosus GG alone and in combination with prebiotics polydextrose and galactooligosaccharide in male rats exposed to early-life stress.

Early life is a period of significant brain development when the brain is at its most plastic and vulnerable. Stressful episodes during this window of development have long-lasting effects on the central nervous system. Rodent maternal separation (MS) is a reliable model of early-life stress and induces alterations in both physiology and behaviour.

Dietary Prebiotics and Bioactive Milk Fractions Improve NREM Sleep, Enhance REM Sleep Rebound and Attenuate the Stress-Induced Decrease in Diurnal Temperature and Gut Microbial Alpha Diversity.

Severe, repeated or chronic stress produces negative health outcomes including disruptions of the sleep/wake cycle and gut microbial dysbiosis. Diets rich in prebiotics and glycoproteins impact the gut microbiota and may increase gut microbial species that reduce the impact of stress. This experiment tested the hypothesis that consumption of dietary prebiotics, lactoferrin (Lf) and milk fat globule membrane (MFGM) will reduce the negative physiological impacts of stress.

Early life diet containing prebiotics and bioactive whey protein fractions increased dendritic spine density of rat hippocampal neurons.

Early life nutrition plays an important role in brain development. Emerging research in rodents, piglets and humans suggest that prebiotics, milk fat globule membrane and lactoferrin may each play unique roles in brain development and cognitive functions. However, knowledge of their combined impact is lacking.

Early life diets with prebiotics and bioactive milk fractions attenuate the impact of stress on learned helplessness behaviours and alter gene expression within neural circuits important for stress resistance.

Manipulating gut microbes may improve mental health. Prebiotics are indigestible compounds that increase the growth and activity of health-promoting microorganisms, yet few studies have examined how prebiotics affect CNS function. Using an acute inescapable stressor known to produce learned helplessness behaviours such as failure to escape and exaggerated fear, we tested whether early life supplementation of a blend of two prebiotics, galactooligosaccharide (GOS) and polydextrose (PDX), and the glycoprotein lactoferrin (LAC) would attenuate behavioural and biological responses to stress later in life.

Porcine Milk Oligosaccharides and Sialic Acid Concentrations Vary Throughout Lactation.

Background: Milk oligosaccharides (OSs) are bioactive components known to influence neonatal development. These compounds have specific physiological functions acting as prebiotics, immune system modulators, and enhancing intestine and brain development.

Objectives: The pig is a commonly used model for studying human nutrition, and there is interest in quantifying OS composition of porcine milk across lactation compared with human milk.