Acting is the key: new directions for the stimulation of prospective memory in mild cognitive impairment

Background: The fulfillment of delayed intended actions (e.g. taking medication or attending an appointment) is described in the literature as prospective memory (PM), and is often pointed out as a fairly common concern for healthy adults in everyday life constituting a fundamental requirement for independent living across the lifespan. PM may be compromised in the course of healthy aging and may be particularly disrupted very early in the neurodegenerative process, namely at the stage of Mild Cognitive Impairment (MCI), which usually represents an initial phase of Alzheimer’s disease (AD), severely affecting a self-sufficient life-style and causing immense apprehension to caregivers. Methods: We have addressed this issue by investigating whether enactment at encoding could improve PM performance and whether these potential benefits were dependent of the relationship between the retrieval cue and its associated action. We report findings that explored this hypothesis in 64 young adults aged 18-39 years (M ¼ 20.41, SD ¼ 3.553) and 64 educationally matched older adults aged 58-90 years (M ¼ 71.17, SD ¼ 7.204) using a behavioral PM testing paradigm with a 2 X 2 X 2 between-subject factorial design. Results: Older adults’ PM performance (like that of their younger counterparts) benefited from enactment at encoding and from a strong semantic cue-action relation. Furthermore, there were no reliable effects of encoding modality or cue-action relatedness on performance accuracy or speed, despite a generalized slowness associated with age. Importantly, these beneficial effects were maintained across the lifespan, and even under high attentional demands. Figure 1. Mean proportion of PM cues eliciting a correct response at the appropriate moment in each Method of Encoding X Cue-Action Relatedness X Ag

Chemistry and transport of silver nanoparticles in environmentally relevant conditions

The fate and transport of citrate and PVP silver nanoparticles (AgNPs) was determined using large scale mesocosm studies with synthetic water and seasonal variations of natural lake water. We were able to produce a simple diffusion-sedimentation mathematical model which modifies sedimentation and diffusion equations for particles moving through a column. We introduced AgNP parameters including size and starting concentration to predict concentration and infer transport mechanisms in a 1 meter tall column over time. Ionic strength had a direct impact upon the behaviour and transformations observed by the two different surface coated AgNPs. Water collected in summer contained high TOC concentrations with low ionic strength. We observed increased stability to the citrate AgNPs and PVP AgNPs remained as nanoparticles for the duration of the study in the surface water. Winter water had the lowest TOC concentrations with high ionic strength. Citrate AgNPs showed increased aggregation and dissolution, whereas the PVP AgNPs remained stable. At different times of the year the transformations of the NPs change and during the warmer months AgNPs persist in particulate forms for longer periods of time in the surface waters

Nanodentistry: The benefits of nanotechnology in dentistry and its impact on oral health

Nanotechnology is a multidisciplinary field that covers a variety of technological advancements. This branch of technology operates on objects that are less than one billionth of a meter which is equal to one nanometer, therefore focusing its job at the molecular and atomic level. The application of nanotechnology was primarily used in medicine however the emergence of nanodentistry has enabled dental technicians to modify various nanotechnologies to specify them to the field of dentistry. These advancements greatly impact the way dentists go about diagnosing patients, and in doing so using the proper material in order to improve patient treatment. Nanodentistry provides dentists with a new alternative approach that can be applied in their dental practice to treat oral health related problems with a higher degree of specificity.The applications of nanodentistry are designed to achieve maximum therapeutic efficacy with minimal side effects. There are several devices that are used to treat periodontal related illnesses, perform tissue regeneration and bone grafting. Some of these devices include: nanoparticles, nanoassemblers and nanocrystalline hydroxyapatite. These technological devices play an imperative role in helping dentists and dental technicians to analyze information and make precise judgments in the treatment of patients to improve their oralhealth and wellbeing while identifying ineffective current methods.La nanotechnologie est un domaine pluridisciplinaire qui couvre une variété de progrès technologiques. Cette division de la technologie règle des objets de moins d’un milliardième de mètre de largeur (égale à un nanomètre) et se concentre sur les niveaux moléculaires et atomiques. La nanotechnologie est principalement utilisée enmédecine, cependant, l’émergence de la nanodentisterie a permis aux techniciens dentaires de modifier diverses nanotechnologies pour les adapter au domaine de la dentisterie. Ces progrès ont un impact significatif sur la façon dont les dentistes diagnostiquent les patients et utilisent le matériel approprié pour améliorer le traitement des patients. La nanodentisterie fournit une nouvelle approche aux dentistes qui peut être appliquée dans la pratique dentaire pour traiter les problèmes de santé bucco-dentaire avec un degré plus élevé de précision. Les applications de nanodentisterie sont conçues pour atteindre une efficacité thérapeutique maximale tout en minimisant les effets secondaires. Il existe plusieurs dispositifs utilisés pour traiter les maladies parodontales eteffectuer la régénération tissulaire et la greffe osseuse. Certains de ces dispositifs incluent les nanoparticules, les nanoassembleurs et la hydroxyapatite nanocristalline. Ces dispositifs technologiques jouent un rôle impératif en aidant les dentistes et les techniciens dentaires à analyser l’information et à faire des jugements précis lors du traitement des patients. Ils peuvent améliorer la santé bucco dentaire et le bien-être des patients tout en identifiant les méthodes courantes inefficaces

Cryptococcal Meningitis and Tuberculous Meningitis Co-infection in HIV-Infected Ugandan Adults.

We report 5 HIV-infected Ugandan adults with cryptococcal and tuberculous (TB) meningitis co-infection. All unmasked meningitis occurred within 5 weeks of starting HIV therapy. Xpert MTB/RIF Ultra facilitated prompt diagnosis; however, 60% in-hospital mortality occurred. TB meningitis coinfection prevalence was 0.8% (5/586) among cryptococcal meningitis, 2 during second cryptococcal episodes

Ophthalmic signs in Ugandan adults with HIV-associated cryptococcal meningitis: A nested analysis of the ASTRO-CM cohort.

Cryptococcal meningitis is a leading cause of morbidity and mortality among HIV-infected persons, accounting for 15% of AIDS-related deaths. Visual disturbance is commonly reported, and a wide range of ophthalmic signs may be present on examination. There is limited published literature to date describing the range and incidence of ophthalmic signs in HIV-associated cryptococcal meningitis. Nested within the Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis (ASTRO-CM) trial (ClinicalTrials.gov number: NCT01802385), we conducted an observational study of 696 Ugandan adults with HIV-associated cryptococcal meningitis. Patients were screened for visual disturbance and external ophthalmic signs at initial presentation and at follow-up appointments over 18 weeks. Assessment comprised simple clinical history and basic examination and required no specialist equipment. More than a quarter of our cohort demonstrated ocular signs or symptoms, which were observed throughout the study period.  A broad range of ocular signs were demonstrated: these included neurological signs (10.9%), localized ocular pathology (4.5%), and evidence of concurrent systemic disease (12.9%). The range of signs observed demonstrates the complexities of case management in patients with advanced HIV and cryptococcosis and also the importance of basic ocular examination in low resource settings. There remains an urgent need for studies conducting comprehensive ocular examination in patients with HIV-associated cryptococcal meningitis; these studies should include formal assessment of visual acuity, slit lamp examination and dilated indirect ophthalmoscopy. Prospective studies should investigate whether there is a correlation between reported visual disturbance and objective signs, in order to further clarify the underlying mechanisms and to guide effective diagnosis, follow-up and management

Enhancing prospective memory in mild cognitive impairment: The role of enactment

Introduction: Prospective memory (PM) is a fundamental requirement for independent living which might be prematurely compromised in the neurodegenerative process, namely in mild cognitive impairment (MCI), a typical prodromal Alzheimer’s disease (AD) phase. Most encoding manipulations that typically enhance learning in healthy adults are of minimal benefit to AD patients. However, there is some indication that these can display a recall advantage when encoding is accompanied by the physical enactment of the material. The aim of this study was to explore the potential benefits of enactment at encoding and cue-action relatedness on memory for intentions in MCI patients and healthy controls using a behavioral PMexperimental paradigm. Method: We report findings examining the influence of enactment at encoding for PM performance in MCI patients and age- and education-matched controls using a laboratory-based PM task with a factorial independent design. Results: PM performance was consistently superior when physical enactment was used at encoding and when target–action pairs were strongly associated. Importantly, these beneficial effects were cumulative and observable across both a healthy and a cognitively impaired lifespan as well as evident in the perceived subjective difficulty in performing the task. Conclusions: The identified beneficial effects of enacted encoding and semantic relatedness have unveiled the potential contribution of this encoding technique to optimize attentional demands through an adaptive allocation of strategic resources. We discuss our findings with respect to their potential impact on developing strategies to improve PM in AD sufferers

Effect of Oligopeptide Orientation on Polymer-based DNA Delivery

Non-viral synthetic gene therapy reagents offer excellent structural and chemical versatility within non-immunogenic delivery systems, coupled with high therapeutic gene carrying capacity and long shelf life, making them attractive alternatives to viral systems. The success of non-viral transfection using polymers hinges on efficient nuclear uptake of nucleic acid cargo and overcoming intra- and extracellular barriers. This poster will describe the integration of the PKKKRKV heptapeptide (the Simian virus SV40 large T-antigen nuclear localization sequence, NLS) onto a polymer backbone, and the resultant high reporter gene expression in mice when administered by intramuscular ultrasound-mediated delivery. These novel polymers afforded protein expression higher than JetPEI™ in vivo, and in cell culture outperformed commercial reagents JetPEI™ and Lipofectamine 2000™, the latter being notorious for coupling high transfection efficiency with cytotoxicity. The orientation of the NLS peptide grafts relative to the polymer backbone markedly affected transfection performance both in vitro and in vivo. Quantitative polymerase chain reaction (qPCR) studies on transfected cells showed that polymers having the NLS attached at the valine residue afforded higher nuclear translocation, and subsequently higher protein expression, relative to those having the NLS groups attached in the opposite orientation. Besides nuclear uptake, the superior binding characteristics of these comb polymers compared to linear polylysine, as judged by atomistic and coarse grain simulations as well as polymer-DNA binding experiments, contributes to their enhanced transfection performance. Polyplexes formed from these comb polymer structures exhibit low cytotoxicity and high transfection efficiency both in vitro and in vivo, demonstrating the therapeutic promise of these novel gene therapy reagents