Comparison of Hemodialysis and Peritoneal Dialysis Outcomes in the Older Patient Population

The objective of this research and systematic literature review is to determine the dialysis modality of choice for elderly patients with end-stage renal disease. This literature review will compare the outcomes of hemodialysis and peritoneal dialysis, which will be judged by morbidity, mortality, and quality of life. In this review, PubMed, Embase, and DynaMed were searched using a specific set of keywords and mesh headings. Results of the searches were then filtered to include human-only studies, patients over 65 years old, and published within the last ten years. There were 12 studies that met inclusion criteria and were selected for this literature review. The studies suggested that there were similar outcomes in elderly patients receiving hemodialysis and peritoneal dialysis, and it was concluded that dialysis modality selection should be made on an individual patient basis. The choice between hemodialysis and peritoneal dialysis should be made after first considering each patient’s goals of healthcare, co-morbid conditions, and life experiences. The dialysis modalities should be discussed between the provider and the patient in detail, and a joint decision regarding dialysis modality selection can then be made. Lastly, barriers should be identified so that they can be overcome with proper education, counseling, and assistance. These steps will allow the older patient to be successful with their selected dialysis modality

Comparison of Hemodialysis and Peritoneal Dialysis Outcomes in the Older Adult Patient

The objective of this research and systematic literature review was to determine the dialysis modality of choice for elderly patients with end-stage renal disease. This literature review compared the outcomes of hemodialysis and peritoneal dialysis, which was judged by morbidity, mortality, and quality of life. • PubMed, Embase, and DynaMedwere searched using a specific set of keywords and mesh headings. Results of the searches were then filtered to include human-only studies, patients over 65 years old, and published within the last ten years. There were 12 studies that met inclusion criteria and were selected. • The studies suggested that there were similar outcomes in elderly patients receiving hemodialysis and peritoneal dialysis. It was concluded that dialysis modality selection should be made on an individual patient basis after first considering each patient’s goals of healthcare, co-morbid conditions, and life experiences. The different dialysis modalities should be discussed between the provider and the patient in detail, and a joint decision can then be made. • Lastly, barriers should be identified so that they can be overcome with proper education, counseling, and assistance. These steps will allow the patient to be successful with their selected dialysis modality.https://commons.und.edu/pas-grad-posters/1234/thumbnail.jp

Overexpression of IL-10 in C2D macrophages promotes a macrophage phenotypic switch in adipose tissue environments

Adipose tissue macrophages are a heterogeneous collection of classically activated (M1) and alternatively activated (M2) macrophages. Interleukin 10 (IL-10) is an anti-inflammatory cytokine, secreted by a variety of cell types including M2 macrophages. We generated a macrophage cell line stably overexpressing IL-10 (C2D-IL10) and analyzed the C2D-IL10 cells for several macrophage markers after exposure to adipocytes compared to C2D cells transfected with an empty vector (C2D-vector). C2D-IL10 macrophage cells expressed more CD206 when co-cultured with adipocytes than C2D-vector cells; while the co-cultured cell mixture also expressed higher levels of Il4, Il10, Il1β and Tnf. Since regular C2D cells traffic to adipose tissue after adoptive transfer, we explored the impact of constitutive IL-10 expression on C2D-IL10 macrophages in adipose tissue in vivo. Adipose tissue-isolated C2D-IL10 cells increased the percentage of CD206+, CD301+, CD11c−CD206+ (M2) and CD11c+CD206+ (M1b) on their cell surface, compared to isolated C2D-vector cells. These data suggest that the expression of IL-10 remains stable, alters the C2D-IL10 macrophage cell surface phenotype and may play a role in regulating macrophage interactions with the adipose tissue

Effects of prenatal low protein and postnatal high fat diets on visceral adipose tissue macrophage phenotypes and IL-6 expression in Sprague Dawley rat offspring

Adipose tissue macrophages (ATM) are implicated in adipose tissue inflammation and obesity-related insulin resistance. Maternal low protein models result in fetal programming of obesity. The study aims to answer whether maternal undernutrition by protein restriction affects the ATM M1 or M2 phenotype under postnatal high fat diet in F1 offspring. Using a rat model of prenatal low protein (LP, 8% protein) diet followed by a postnatal high fat energy diet (HE, 45% fat) or low fat normal energy diet (NE, 10% fat) for 12 weeks, we investigated the effects of these diets on adiposity, programming of the offspring ATM phenotype, and the associated inflammatory response in adipose tissue. Fat mass in newborn and 12-week old LP fed offspring was lower than that of normal protein (20%; NP) fed offspring; however, the adipose tissue growth rate was higher compared to the NP fed offspring. While LP did not affect the number of CD68+ or CD206+ cells in adipose tissue of NE offspring, it attenuated the number of these cells in offspring fed HE. In offspring fed HE, LP offspring had a lower percentage of CD11c+CD206+ ATMs, whose abundancy was correlated with the size of the adipocytes. Noteworthy, similar to HE treatment, LP increased gene expression of IL-6 within ATMs. Two-way ANOVA showed an interaction of prenatal LP and postnatal HE on IL-6 and IL-1β transcription. Overall, both LP and HE diets impact ATM phenotype by affecting the ratio of CD11c+CD206+ ATMs and the expression of IL-6

The role of expertise in dynamic risk assessment: A reflection of the problem-solving strategies used by experienced fireground commanders

Although the concept of dynamic risk assessment has in recent times become more topical in the training manuals of most high risk domains, only a few empirical studies have reported how experts actually carry out this crucial task. The knowledge gap between research and practice in this area therefore calls for more empirical investigation within the naturalistic environment. In this paper, we present and discuss the problem solving strategies employed by sixteen experienced operational firefighters using a qualitative knowledge elicitation tool — the critical decision method. Findings revealed that dynamic risk assessment is not merely a process of weighing the risks of a proposed course of action against its benefits, but rather an experiential and pattern recognition process. The paper concludes by discussing the implications of designing training curriculum for the less experienced officers using the elicited expert knowledge

Start2quit: a randomised clinical controlled trial to evaluate the effectiveness and cost-effectiveness of using personal tailored risk information and taster sessions to increase the uptake of the NHS Stop Smoking Services.

BACKGROUND: The NHS Stop Smoking Services (SSSs) offer help to smokers who want to quit. However, the proportion of smokers attending the SSSs is low and current figures show a continuing downward trend. This research addressed the problem of how to motivate more smokers to accept help to quit. OBJECTIVES: To assess the relative effectiveness, and cost-effectiveness, of an intervention consisting of proactive recruitment by a brief computer-tailored personal risk letter and an invitation to a 'Come and Try it' taster session to provide information about the SSSs, compared with a standard generic letter advertising the service, in terms of attendance at the SSSs of at least one session and validated 7-day point prevalent abstinence at the 6-month follow-up. DESIGN: Randomised controlled trial of a complex intervention with follow-up 6 months after the date of randomisation. SETTING: SSSs and general practices in England. PARTICIPANTS: All smokers aged ≥ 16 years identified from medical records in participating practices who were motivated to quit and who had not attended the SSS in the previous 12 months. Participants were randomised in the ratio 3 : 2 (intervention to control) by a computer program. INTERVENTIONS: Intervention - brief personalised and tailored letter sent from the general practitioner using information obtained from the screening questionnaire and from medical records, and an invitation to attend a taster session, run by the local SSS. Control - standard generic letter from the general practice advertising the local SSS and the therapies available, and asking the smoker to contact the service to make an appointment. MAIN OUTCOME MEASURES: (1) Proportion of people attending the first session of a 6-week course over a period of 6 months from the receipt of the invitation letter, measured by records of attendance at the SSSs; (2) 7-day point prevalent abstinence at the 6-month follow-up, validated by salivary cotinine analysis; and (3) cost-effectiveness of the intervention. RESULTS: Eighteen SSSs and 99 practices within the SSS areas participated; 4384 participants were randomised to the intervention (n = 2636) or control (n = 1748). One participant withdrew and 4383 were analysed. The proportion of people attending the first session of a SSS course was significantly higher in the intervention group than in the control group [17.4% vs. 9.0%; unadjusted odds ratio (OR) 2.12, 95% confidence interval (CI) 1.75 to 2.57; p  86% over a lifetime horizon. LIMITATIONS: Participating SSSs may not be representative of all SSSs in England. Recruitment was low, at 4%. CONCLUSIONS: The Start2quit trial added to evidence that a proactive approach with an intensive intervention to deliver personalised risk information and offer a no-commitment introductory session can be successful in reaching more smokers and increasing the uptake of the SSS and quit rates. The intervention appears less likely to be cost-effective in the short term, but is highly likely to be cost-effective over a lifetime horizon. FUTURE WORK: Further research could assess the separate effects of these components. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76561916. FUNDING DETAILS: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 3. See the NIHR Journals Library website for further project information

Creating a Transgenic Goat Model of Familial Lone Atrial Fibrillation

Atrial fibrillation is one of the most common forms of cardiac arrhythmia affecting about 2.3 million people in the U.S. It can lead to a variety of conditions such as thromboembolism, heart failure, and ventricular arrhythmia. These types of conditions can result in death. Though there are many risk factors, AF can be hereditary (lone AF). Many KCNQ1 gain-of-function mutations have been associated with lone AF development, though their effects have only been tested in cultured animal cells and mouse models. Because their organ sizes and physiology are similar to humans, a large animal model of these mutations will greatly advance the study of this disease by providing a more realistic simulation of AF than previous small animal models. The goal of this project is to create the first transgenic goat model of lone AF by inducing the human KCNQ1 mutations S140G, V141M, and Q147R. We have successfully designed and constructed CRISPR vectors targeting an area where these three mutations exist

Creating Genetically Engineered Hamster Models of Atrial Fibrillation and Long QT Syndrome

Atrial fibrillation (AF) and long QT syndrome (LQT) are two leading heart diseases, both of which can be caused by genetic mutations in the KCNQ1 gene. Both conditions can be fatal if left untreated. KCNQ1 codes for a potassium channel subunit in cardiomyocytes responsible for heart repolarization. Many gain-of-function mutations in this gene have been known to cause AF, while loss-of-function mutations cause LQT. By inducing a mutation in the KCNQ1 gene that causes AF or LQT in humans into the hamster genome, we would be able to study these diseases in an effective model organism that has shown to have advantages over other small organisms such as mice. The goal of this research is to create hamster models of AF and LQT by inducing the most prevalent human KCNQ1-mutations into their genomes. We first subcloned and characterized the hamster genomic locus harboring exon 2 of the KCNQ1 gene that corresponds to the human KCNQ1 coding sequence, where AF and LQT-causing mutations occur. Utilizing CRISPR/Cas9 genome editing technology, we have induced a KCNQ1 knockout mutation in hamsters at the cellular level. Experiments to induce the AF-inducing point mutation, Q147R, are also being performed. Establishing cell lines of these modified genomes will provide excellent in vitro models of these heart diseases. Ultimately, the CRISPR/Cas9 technology used to modify these cells will be used created live animals containing these heart disease mutations providing critically needed models of atrial fibrillation and long QT syndrome

Development of Genetic Goat and Hamster Models of Atrial Fibrillation and Long QT Syndrome; and Genetic Hamster Models of Middle East Respiratory Syndrome

Atrial fibrillation, long QT syndrome, and Middle East Respiratory Syndrome are three deadly human diseases for which genetic animal models are needed. From elucidating disease pathogenesis to facilitating the development of treatments, animal models are crucial for studying human disease. One of the most effective ways to generate specific animal models is through genetic modification. Historically, mice have been most widely used as genetically modified models, despite a number of limitations. New gene editing technologies such as CRISPR/Cas9 have made developing alternative genetic models that better recapitulate some human diseases better and more feasible. In this thesis, I describe my efforts to develop genetically modified goat and hamster models for atrial fibrillation and long QT syndrome, and genetically modified hamster models for Middle East Respiratory Syndrome. For long QT syndrome model development, I knocked out the KCNQ1 gene in goat fetal fibroblast cells and baby hamster kidney cells using the CRIPSR/Cas9 system. The knockout results in loss-of-function mutations, a known cause of human long QT syndrome. The edited goat fibroblast cells will be nuclear donors for future cloning experiments to produce live goats possessing the KCNQ1 knockout. The CRISPR gene targeting sgRNA/Cas9 vector, specific for the hamster KCNQ1, has been used for pronuclear injections to produce KCNQ1 knockout hamsters. For atrial fibrillation model development, I designed a single-stranded donor oligonucleotide that generates a KCNQ1 gainof-function mutation resulting in the disease. This oligonucleotide was injected into hamster embryos along with the KCNQ1 sgRNA/Cas9-expressing vector to generate hamsters containing the gain-of-function mutation. Finally, for Middle East Respiratory Syndrome model development, I established a breeding colony of human DPP4 transgenic hamsters in the STAT2 knockout background. Human DPP4 transgenic hamsters are susceptible to MERS-CoV infection, showing mild clinical signs and allowing viral replication in lung tissue. Giving these hamsters a STAT2 knockout background should promote a more severe disease progression. For all three diseases, the foundations for the development of genetic animal models have been laid