Delirium is an acute change in attention and cognition occurring in ~ 65% of severe SARS-CoV-2 cases. It is also common following surgery and an indicator of brain vulnerability and risk for the ...development of dementia. In this work we analyzed the underlying role of metabolism in delirium-susceptibility in the postoperative setting using metabolomic profiling of cerebrospinal fluid and blood taken from the same patients prior to planned orthopaedic surgery. Distance correlation analysis and Random Forest (RF) feature selection were used to determine changes in metabolic networks. We found significant concentration differences in several amino acids, acylcarnitines and polyamines linking delirium-prone patients to known factors in Alzheimer's disease such as monoamine oxidase B (MAOB) protein. Subsequent computational structural comparison between MAOB and angiotensin converting enzyme 2 as well as protein-protein docking analysis showed that there potentially is strong binding of SARS-CoV-2 spike protein to MAOB. The possibility that SARS-CoV-2 influences MAOB activity leading to the observed neurological and platelet-based complications of SARS-CoV-2 infection requires further investigation.
Connected health devices are generally designed for unsupervised use, by non-healthcare professionals, facilitating independent control of the individuals own healthcare. Older adults are major users ...of such devices and are a population significantly increasing in size. This group presents challenges due to the wide spectrum of capabilities and attitudes towards technology. The fit between capabilities of the user and demands of the device can be optimised in a process called Human Centred Design. Here we review examples of some connected health devices chosen by random selection, assess older adult known capabilities and attitudes and finally make analytical recommendations for design approaches and design specifications.
To describe the differences in a range of quantitative OCT angiography (OCTA) metrics across early stages of diabetic retinopathy (DR), providing robust effect estimates as well as sensitivity and ...specificity.
Cross-sectional study with population-based sampling.
Four hundred forty-one eyes from 296 individuals: 328 control eyes (no diabetes mellitus DM and no DR), 55 eyes with DM and no DR, and 58 eyes with early nonproliferative DR.
Multimodal retinal imaging included color fundus photography, color Optomap ultra-widefield imaging, and spectral-domain OCT (Spectralis OCT2; Heidelberg Engineering GmbH) with the OCTA module. All images were graded for the presence and severity of DR features. OCTA images were assessed manually for inclusion based on quality. Binary OCTA metrics were assessed after 3-dimensional projection artifact removal including from the nerve fiber layer vascular plexus, superficial vascular plexus (SVC), and deep vascular plexus (DVC) by Early Treatment Diabetic Retinopathy Study (ETDRS) grid, foveal avascular zone (FAZ) area, FAZ minimum and maximum diameter, perimeter length, and circularity.
Diabetes mellitus and DR status and presence or absence of DR in the retinal periphery.
The reduction in vessel densities in participants with DM and manifest DR compared with control participants tended to be twice that of those with DM, but no DR, compared with control participants. Some evidence of spatial heterogeneity in vessel reductions was found in those yet to develop DR, whereas those with manifest DR had significant reductions across the ETDRS grid. The FAZ perimeter and circularity were impacted most significantly by DM, and those with DR showed decreased multispectral fractal dimensions compared with control participants. Eyes with peripheral DR had reduced vessel density compared with those with DM and no DR only in the superior outer, temporal inner, and temporal outer regions in the DVC and SVC. The area under the receiver operating characteristic curve ranged between 0.48 and 0.73.
Significant differences in OCTA metrics can be found in those with DM before manifest DR using commercially available equipment with minimal image postprocessing. Although diagnostic performance was poor, these metrics may be useful for measuring change over time in clinical trials.
To provide structural and functional evidence of inner retinal loss in diabetes prior to vascular changes and interpret the structure-function relationship in the context of an established neural ...model.
Data from one eye of 505 participants (134 with diabetes and no clinically evident vascular alterations of the retina) were included in this analysis. The data were collected as part of a large population-based study. Functional tests included best-corrected visual acuity, Pelli-Robson contrast sensitivity, mesopic microperimetry, and frequency doubling technology perimetry (FDT). Macular optical coherence tomography volume scans were collected for all participants. To interpret the structure-function relationship in the context of a neural model, ganglion cell layer (GCL) thickness was converted to local ganglion cell (GC) counts.
The GCL and inner plexiform layer were significantly thinner in participants with diabetes (P < 0.05), with no significant differences in the macular retinal nerve fiber layer or the outer retina. All functional tests except microperimetry showed a significant loss in diabetic patients (P < 0.05). Both FDT and microperimetry showed a significant relationship with the GC count (P < 0.05), consistent with predictions from a neural model for partial summation conditions. However, the FDT captured additional significant damage (P = 0.03) unexplained by the structural loss.
Functional and structural measurements support early neuronal loss in diabetes. The structure-function relationship follows the predictions from an established neural model. Functional tests could be improved to operate in total summation conditions in the macula, becoming more sensitive to early loss.
We outline an electrodeposition procedure from an emulsion to fabricate novel vertically aligned open and closed-pore microstructures of poly(N-(2-cyanoethyl)pyrrole) (PPyEtCN) at an electrode ...surface. Adsorbed toluene droplets were employed as soft templates to direct polymer growth. The microstructures developed only in the presence of both ClO4 – and H2PO4 – doping ions due to a slower rate of polymer propagation in this electrolyte. Two sonication methods (probe and bath) were used to form the emulsion, producing significantly different microstructure morphologies. Control over microtube diameter can be achieved by simply altering the emulsion sonication time or the amount of toluene added to form the emulsion. Electrochemical characterization indicated the PPyEtCN microtube morphology had an increased electrochemical response compared to its bulk counterpart. TEM analysis of individual closed-pore microtubes identified a hollow interior at the base within which the toluene droplet was encapsulated. This cavity may be used to entrap other compounds making these materials useful in a range of applications. The methodology was also applied to form microstructures of poly(3,4-ethylenedioxythiophene) and polypyrrole.
A key pathological feature of late-onset Alzheimer's disease (LOAD) is the abnormal extracellular accumulation of the amyloid-β (Aβ) peptide. Thus, altered Aβ degradation could be a major contributor ...to the development of LOAD. Variants in the gene encoding the Aβ-degrading enzyme, angiotensin-1 converting enzyme (ACE) therefore represent plausible candidates for association with LOAD pathology and risk. Following Alzgene meta-analyses of all published case-control studies, the ACE variants rs4291 and rs1800764 showed significant association with LOAD risk. Furthermore ACE haplotypes are associated with both plasma ACE levels and LOAD risk. We tested three ACE variants (rs4291, rs4343, and rs1800764) for association with LOAD in ten Caucasian case-control populations (n = 8,212). No association was found using multiple logistic models (all p > 0.09). We found no population heterogeneity (all p > 0.38) or evidence for association with LOAD risk following meta-analysis of the ten populations for rs4343 (OR = 1.00), rs4291 (OR = 0.97), or rs1800764 (OR = 0.99). Although we found no haplotypic association in our complete dataset (p = 0.51), a significant global haplotypic p-value was observed in one population (p = 0.007) due to an association of the H3 haplotype (OR = 0.72, p = 0.02) and a trend towards an association of H4 (OR = 1.38, p = 0.09) and H7 (OR = 2.07, p = 0.08) although these did not survive Bonferroni correction. Previously reported associations of ACE variants with LOAD will be diminished following this study. At best, ACE variants have modest effect sizes, which are likely part of a complex interaction between genetic, phenotypic and pharmacological effects that would be undetected in traditional case-control studies.
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