The Interaction between Nef Protein and ABCA1 Mutants in Tangier Disease

The genetic disorder Tangier Disease is characterized by mutations at a chromosomal locus, 9q31, which affect proper function of the cholesterol transporter ATP-Binding Cassette A1 (ABCA1). Individuals with mutant ABCA1 have very low levels of high-density lipoprotein and are at high risk for development of neuropathy and atherosclerosis. Two of the ABCA1 mutations, Q597R and R587W, lead to retention of ABCA1 in the endoplasmic reticulum (ER) in a pattern that is reminiscent of a previously reported ABCA1 inactivation by HIV-1 protein Nef. The mechanism of that inactivation involves Nef binding to an ER chaperone calnexin, which disrupts the interaction between calnexin and ABCA1 preventing proper maturation of ABCA1. As a result, ABCA1 is retained in the ER and not transported to the plasma membrane where its main activity takes place. Thus, we speculated that the underlying mechanism of retention of ABCA1 in the ER of patients with Q597R and R587W mutations is caused by a weakened interaction between mutated ABCA1 and calnexin. However, our preliminary data suggests that it is actually an abnormally strong interaction between these two molecules that leads to the retention of ABCA1 in the ER. The main aim of my research is to attempt to use HIV-1 Nef to decrease the strength of interaction between these mutants and calnexin, which may enable the transport of ABCA1 molecules to cellular membrane, thus restoring the cholesterol efflux from the affected cells. If successful, this approach could lead to a potential therapeutic treatment for Tangier disease using Nef-mimicking peptides

Implementation of a Finger Foods Diet for Adults with Dementia

Dementia is a general term for a decline in mental ability severe enough to affect memory, thinking, behavior and the ability to accurately perform everyday activities. Seniors’ eating habits are impacted depending on which stage of dementia they are experiencing. Common signs and symptoms in early-stage dementia include forgetfulness, difficulty communicating thoughts, anxiety and depression, loss of concentration, being unable to recognize spoiled food, changes in food preferences, and an inability to hold attention through a meal. In middle-stage dementia, solutions include: constant redirection to meals and snacks, introducing tablemates as they may not remember their names from last meal, planning a menu to include foods and liquids suitable to this stage of dementia (e.g., finger foods, mechanically altered items, and foods to eat on the go ), maintaining a calm and unhurried environment, serving meals with only a fork or spoon, and continuing to serve meal one course at a time. A finger food diet is regular diet consistency which can be easily eaten with the fingers and not requiring silverware. A Finger Food Diet Menu was developed using similar menu options as a Regular/No Added Salt diet. The existing menu foods were used for two reasons, 1) so that residents did not feel segregated, and 2) to make the best use of foods currently being purchased/utilized. The head chef and registered dietitian worked together on the Finger Food Diet Menu. The limitation to the Finger Food Diet Menu is that it is not appropriate for residents on a mechanical soft or pureed diet

O Parto Normal: Experiências de Portugal e Além-fronteiras

As a result of medical advances and technological developments, childbirth in Europe has been transformed from a physiological process usually taking place in the home, to a pathological, clinical event. This publication is concerned with what constitutes a normal birth in contemporary society, and current cultural influences on childbirth practices. What are the procedures and outcomes, opinions and preferences related to childbirth in different societies, and particularly Portugal? What is the interface between proponents of different approaches to childbirth? And what developments can we expect to see in the immediate future? These issues were discussed by specialists from diverse backgrounds at an international seminar in Lisbon. This e-book includes a general and thematic introduction, a literal transcription of the seminar proceedings and discussions, academic and practical references and a comprehensive bibliography. Each section is presented in both English and Portuguese.info:eu-repo/semantics/publishedVersio

Ulcerative C2 neurocutaneous dysesthesia (trigeminal trophic syndrome in an alternative distribution)

Trigeminal trophic syndrome is an uncommon condition characterized by paresthesia, itch, and self-inflicted wounds following the trigeminal dermatome(s). Similar processes adhering to cervical nerve distributions have been reported, calling into question the specificity of trigeminal trophic syndrome for the trigeminal network. Herein, we report patient with trigeminal trophic syndrome adhering to the C2 dermatome, a previously unreported distribution

The uncertainty contagion: Revealing the interrelated, cascading uncertainties of managed retreat

Managed retreat presents a dilemma for at-risk communities, and the planning practitioners and decisionmakers working to address natural hazard and climate change risks. The dilemma boils down to the countervailing imperatives of moving out of harm’s way versus retaining ties to community and place. While there are growing calls for its use, managed retreat remains challenging in practice—across diverse settings. The approach has been tested with varied success in a number of countries, but significant uncertainties remain, such as regarding who ‘manages’ it, when and how it should occur, at whose cost, and to where? Drawing upon a case study of managed retreat in New Zealand, this research uncovers intersecting and compounding arenas of uncertainty regarding the approach, responsibilities, legality, funding, politics and logistics of managed retreat. Where uncertainty is present in one domain, it spreads into others creating a cascading series of political, personal and professional risks that impact trust in science and authority and affect people’s lives and risk exposure. In revealing these mutually dependent dimensions of uncertainty, we argue there is merit in refocusing attention away from policy deficits, barrier approaches or technical assessments as a means to provide ‘certainty’, to instead focus on the relations between forms of knowledge and coordinating interactions between the diverse arenas: scientific, governance, financial, political and socio-cultural; otherwise uncertainty can spread like a contagion, making inaction more likely

Water and Life. A Cross-Sectional Study on Determinants of Beverage Consumption and Water Access in One Tribal Community

Increasingly, poor diet has been shown to be one of the most crucial factors associated with cause of death, even more critical than smoking. Research in the past two decades has consistently linked increased consumption of sugar-sweetened beverages (SSB) to the obesity epidemic contributing to a public health crisis all over the United States. Native Americans, among other minority groups, suffer obesity disproportionately from the rest of the US population, yet they continually fail to be included in research on the subject. Traditional research methods, sparse care coverage on reservations, consolidation of unique tribes into one classification, and failure to include cultural and historical contexts in research analysis have led to a failure to both clearly define the cause of the disparity, and furthermore, to provide for closing the gap. This study utilized the results of a cross-sectional survey on drinking habits and water access in one tribal reservation to determine prevalence of SSB consumption and its relationship to identification as Native American. Multivariate logistic regression analysis, after accounting for covariates, identified characteristics which significantly impacted odds of consumption. Prevalence of daily SSB consumption was determined to be 69.4% (± 4.7%). Odds of daily soda and SSB consumption were 3 to 4 times greater in Native Americans than other ethnicities. Non-natives were four times more likely to consume water daily. Body mass index was positively correlated with daily soda consumption, and older individuals experienced greater odds of heavy SSB consumption (\u3e4 SSBs consumed per day). Individuals with less than a college education were at greater odds of daily SSB consumption. Contrary to the literature, gender and income were uncorrelated to consumption. This study was the first of its kind to establish a baseline statistic for prevalence and determinants of SSB consumption in a tribal community

Oligodendroglial Argonaute protein Ago2 associates with molecules of the Mbp mRNA localization machinery and is a downstream target of Fyn kinase

Oligodendrocytes myelinate neuronal axons in the central nervous system (CNS) facilitating rapid transmission of action potentials by saltatory conduction. Myelin basic protein (MBP) is an essential component of myelin and its absence results in severe hypomyelination in the CNS of rodents. Mbp mRNA is not translated immediately after exit from the nucleus in the cytoplasm, but is transported to the plasma membrane in RNA transport granules in a translationally silenced state. We have previously identified the small non-coding RNA 715 (sncRNA715) as an inhibitor of Mbp translation associated with RNA granules. Argonaute (Ago) proteins and small RNAs form the minimal core of the RNA induced silencing complex and together recognize target mRNAs to be translationally inhibited or degraded. Recently, tyrosine phosphorylation of Ago2 was reported to be a regulator of small RNA binding. The oligodendroglial non-receptor tyrosine kinase Fyn is activated by neuronal signals and stimulates the translation of Mbp mRNA at the axon-glial contact site. Here we analyzed the expression of Ago proteins in oligodendrocytes, if they associate with Mbp mRNA transport granules and are tyrosine phosphorylated by Fyn. We show that all Ago proteins (Ago1-4) are expressed by oligodendrocytes and that Ago2 colocalizes with hnRNP A2 in granular cytoplasmic structures. Ago2 associates with hnRNP A2, Mbp mRNA, sncRNA715 and Fyn kinase and is tyrosine phosphorylated in response to Fyn activity. Our findings suggest an involvement of Ago2 in the translational regulation of Mbp. The identification of Ago proteins as Fyn targets will foster further research to understand in more molecular detail how Fyn activity regulates Mbp translation

Analyzing the Clinical Outcomes of a Rapid Mass Conversion From Rosuvastatin to Atorvastatin in a VA Medical Center Outpatient Setting

Background: Medication conversions occur frequently within the Veterans Health Administration. This manual process involves several pharmacists over an extended period of time. Macros can automate the process of converting a list of patients from one medication to a therapeutic alternative. Objectives: To develop a macro that would convert active rosuvastatin prescriptions to atorvastatin and to create an electronic dashboard to evaluate clinical outcomes. Methods: A conversion protocol was approved by the Pharmacy & Therapeutics Committee. A macro was developed using Microsoft Visual Basic. Outpatients with active prescriptions for rosuvastatin were reviewed and excluded if they had a documented allergy to atorvastatin or a significant drug-drug interaction. An electronic dashboard was created to compare safety and efficacy endpoints pre- and postconversion. Primary endpoints included low-density lipoprotein (LDL), creatine phosphokinase (CPK), aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase. Secondary endpoints evaluated cardiovascular events, including the incidences of myocardial infarction, stroke, and stent placement. Results: The macro was used to convert 1520 patients from rosuvastatin to atorvastatin over a period of 20 hours saving $5760 in pharmacist labor. There were no significant changes in LDL, AST, ALT, or secondary endpoints (P > .05). There was a significant increase in alkaline phosphatase (P = .0035). Conclusions: A rapid mass medication conversion from rosuvastatin to atorvastatin saved time and money and resulted in no clinically significant changes in safety or efficacy endpoints. Macros and clinical dashboards can be applied to any Veterans Health Administration facility

Stakeholder engagement and the diffusion of childbirth knowledge: experiences of the COST project.

Poster presenting the diverse actions in various European countries, participating in the project COST IS0907, to promote improvement in childbirth procedures and conditions. Seminars were organized between 2011 and 2013 as an offshoot of COST Action IS0907, “Childbirth Cultures, Concerns and Consequences: Creating a Dynamic EU Framework for optimal maternity care”. The aim of these events was to engage various stakeholders in exchanging research and experiences related to the improvement of maternity practice in each country setting. Different approaches were pursued. This installation aims to share what took place at the seminars.info:eu-repo/semantics/publishedVersio