Changes in insulin and insulin signaling in Alzheimer\u27s disease: Cause or consequence?

Individuals with type 2 diabetes have an increased risk for developing Alzheimer’s disease (AD), although the causal relationship remains poorly understood. Alterations in insulin signaling (IS) are reported in the AD brain. Moreover, oligomers/fibrils of amyloid-β (Aβ) can lead to neuronal insulin resistance and intranasal insulin is being explored as a potential therapy for AD. Conversely, elevated insulin levels (ins) are found in AD patients and high insulin has been reported to increase Aβ levels and tau phosphorylation, which could exacerbate AD pathology. Herein, we explore whether changes in ins and IS are a cause or consequence of AD

The problem of interpretation in vignette methodology in research with young people

In this paper we explore how interpretation is dealt with by researchers using a vignette methodology. Researchers using vignette methodology often struggle with interpretation: how to interpret the responses when participants shift between discussing the vignettes as themselves, taking the perspective of the character in the vignette and commenting on what ‘ought’ to happen. We argue that by foregrounding a consideration of the method with an explicitly articulated theoretical position of dialogicality, issues inherent in interpretation become a valuable addition to the research rather than an obstacle to be overcome. In the paper we discuss ‘Louise’ a young carer, detailing the various positions she takes in her talk about the vignette of Mary, a fictitious young carer, to illustrate how a perspective based in dialogical theory contributed to the analysis of her various moves through different identity positions

Anti-Inflammatory System for Subcutaneous Biosensors

An anti-inflammatory system was created to reduce the inflammation and fibrotic scarring caused by a subcutaneous biosensor. This system was comprised of Titania nanotubes, chitosan hydrogel, and drug-releasing nanoparticles, and was aimed at reducing the adhesion and activation of macrophages. Testing suggests that the system reduces macrophage activity, and therefore the subsequent fibrotic encapsulation, in comparison to Ti foil, TiO2 nanotubes, and chitosan hydrogel acting in isolation

Ambiskew Hopf algebras

Necessary and sufficient conditions are obtained for an ambiskew polynomial algebra A over a Hopf k-algebra R to possess the structure of a Hopf algebra extending that of R, in which the added variables X+ and X- are skew primitive. The coradical filtration is calculated, many examples are described, and properties determined

The effects of peripheral and central high insulin on brain insulin signaling and amyloid-β in young and old APP/PS1 mice

Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APP(swe)/PS1(dE9) transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls. We could detect no increase in brain, ISF, or CSF insulin or brain insulin signaling in response to peripheral hyperinsulinemia, despite detecting increased signaling in the muscle. Next, we delivered insulin directly into the hippocampus of young APP/PS1 mice via reverse microdialysis. Brain tissue insulin and insulin signaling was dose-dependently increased, but ISF Aβ was unchanged by central insulin administration. Finally, to determine whether peripheral and central high insulin has differential effects in the presence of significant amyloid pathology, we repeated these experiments in older APP/PS1 mice with significant amyloid plaque burden. Postprandial insulin clamps increased ISF and plasma Aβ, whereas direct delivery of insulin to the hippocampus significantly increased tissue insulin and insulin signaling, with no effect on Aβ in old mice. These results suggest that the brain is still responsive to insulin in the presence of amyloid pathology but increased insulin signaling does not acutely modulate Aβ in vivo before or after the onset of amyloid pathology. Peripheral hyperinsulinemia modestly increases ISF and plasma Aβ in young and old mice, independent of neuronal insulin signaling. SIGNIFICANCE STATEMENT The transportation of insulin from blood to brain is a saturable process relevant to understanding the link between hyperinsulinemia and AD. In vitro experiments have found direct connections between high insulin and extracellular Aβ, but these mechanisms presume that peripheral high insulin elevates brain insulin significantly. We found that physiological hyperinsulinemia in awake, behaving mice does not increase CNS insulin to an appreciable level yet modestly increases extracellular Aβ. We also found that the brain of aged APP/PS1 mice was not insulin resistant, contrary to the current state of the literature. These results further elucidate the relationship between insulin, the brain, and AD and its conflicting roles as both a risk factor and potential treatment

Identifying experiences of supportive care of children and young people affected by kidney failure: a qualitative systematic review.

Children and young people affected by kidney failure experience complexities in their care. Little is known about the unique needs of this young patient population group living with a long-term condition. A meta-aggregation of all qualitative studies was conducted to identify experiences of supportive care among children and young people living with kidney failure. A systematic review of qualitative studies was conducted following the Joanna Briggs Institute meta-aggregation method. This review has been reported according to the PRISMA statement guidelines. Six electronic databases (CINAHL, Cochrane Library, MEDLINE, Proquest, PsycINFO, and Scopus) were comprehensively searched by an expert systematic review librarian using keywords and subject headings, from inception to September 2022. All studies were accessed using a predetermined inclusion and exclusion criteria. Methodological quality assessment and data extraction performed. Qualitative findings accompanied by illustrative quotes from included studies were extracted and grouped into categories which created the overall synthesised findings. A total of 34 studies were included in this review representing a total of 613 children and young people affected by kidney failure. There was a total of 190 findings which created 13 categories representing experiences of supportive care. The meta-aggregation developed five synthesised findings namely: 'physical needs', 'information and technology', 'treatment and healthcare', 'social needs' and 'psychological impacts'. This systematic review identified that children and young people affected by kidney failure can experience a range of unmet supportive care needs in routine clinical services. Kidney failure impacted children and young people's self-identify, social and peer networks, introduced daily practical needs because of inherent physical and psychological burden due to the failure and associated treatments. Despite improvements in the medical management of kidney failure in children and young people, further attention is needed to optimise supported self-management in this young patient group

On the cyclically fully commutative elements of Coxeter groups

Let W be an arbitrary Coxeter group. If two elements have expressions that are cyclic shifts of each other (as words), then they are conjugate (as group elements) in W. We say that w is cyclically fully commutative (CFC) if every cyclic shift of any reduced expression for w is fully commutative (i.e., avoids long braid relations). These generalize Coxeter elements in that their reduced expressions can be described combinatorially by acyclic directed graphs, and cyclically shifting corresponds to source-to-sink conversions. In this paper, we explore the combinatorics of the CFC elements and enumerate them in all Coxeter groups. Additionally, we characterize precisely which CFC elements have the property that powers of them remain fully commutative, via the presence of a simple combinatorial feature called a band. This allows us to give necessary and sufficient conditions for a CFC element w to be logarithmic, that is, ℓ(wk)=k⋅ℓ(w) for all k≥1, for a large class of Coxeter groups that includes all affine Weyl groups and simply laced Coxeter groups. Finally, we give a simple non-CFC element that fails to be logarithmic under these conditions

Mapping and Monitoring of Submerged Aquatic Vegetation in Escambia-Pensacola Bay System, Florida

Recently, the distribution and changes in submerged aquatic vegetation (SAY) in the Escambia-Pensacola Bay System in northeastern Florida were monitored by two techniques. One technique used divers to measure changes in the deepwater margin of beds and provided horizontal growth measurements to the nearest centimeter, the other used a differential global positioning system (DGPS) on a small boat to map the perimeter of SAY beds in shallow water. Current distribution of SAY in Escambia Bay shows that most of the SAY losses that occurred during the 1950s to 1970s have been recovered. In Santa Rosa Sound and Pensacola Bay, SAY showed significant increased growth with horizontal growth rates of some beds averaging more than 50 em over the past year. In Big Lagoon, however, SAY has declined an average of 10 em in horizontal coverage along the deepwater edge. Water quality and photosynthetically active radiation light measurements from the Escambia-Pensacola Bay System suggest that increased light availability was associated with the increased seagrass coverage in Santa Rosa Sound and Pensacola Bay, and elevated nutrient concentrations were associated with the seagrass declines in Big Lagoon