The relationship between anxiety and levels of Alzheimer's disease plasma biomarkers.

Anxiety is highly prevalent in Alzheimer's disease (AD), correlating with CSF/PET biomarkers and disease progression. Relationships to plasma biomarkers are unclear. Herein, we compare levels of plasma biomarkers in research participants with and without anxiety at cognitively normal, mild cognitive impairment, and AD dementia stages. We observed significantly higher plasma tau/Aß42 ratio in AD participants with anxiety versus those without, but did not observe differences at other stages or plasma biomarkers. No such relationships were evident with depression. These results support a unique pathophysiological relationship between anxiety and AD that can be reflected in plasma biomarkers, suggestive of heightened neurodegeneration.

Barriers and Concerns that Contribute to Vaccine Hesitancy in Black, Indigenous, and People of Colour (BIPOC) Individuals in Ontario, Canada.

BACKGROUND: Despite research demonstrating the effectiveness of COVID-19 vaccines, hesitancy is extremely common in minority communities. The purpose of this study was to identify key barriers and concerns that contribute to vaccine hesitancy in Black, Indigenous, and People of Colour (BIPOC) individuals and provide recommendations to address these barriers and concerns. METHODS: The study was an online cross-sectional survey conducted among 1491 BIPOC and Caucasian adults, recruited using social media networks in August-September 2021. The questionnaire consisted of five sections that probed concerns and attitudes contributing to COVID-19 vaccine hesitancy. RESULTS: Respondents were mostly Caucasian males (75.7%) and the average age was 29.1 years. A higher proportion of BIPOC respondents received both doses (50.6%) than Caucasian respondents (36.4%). Out of the unvaccinated, a higher percentage of BIPOC respondents did not plan on getting vaccinated (17.1%) compared to Caucasian respondents (4.2%). BIPOC respondents preferred the Pfizer-BioNTech (34.1%) vaccine whereas Caucasian respondents preferred AstraZeneca (29.3%). The biggest concern BIPOC and Caucasian respondents had with COVID-19 vaccines were side effects (56.6% vs 54.4%, respectively). BIPOC respondents identified dependability as the next biggest concern after side effects. A higher percentage of BIPOC respondents were against getting vaccinated against COVID-19 (16% vs 1.2%) compared to Caucasian respondents. CONCLUSION: Among unvaccinated respondents, COVID-19 vaccine hesitancy was most evident in the BIPOC respondents compared to Caucasian respondents. Side effects, trustworthiness, and lack of information were identified as the three most common concerns surrounding vaccines in general. Increased accessibility to reliable and accurate vaccine information in various languages/dialects can raise awareness about COVID-19 vaccinations in BIPOC communities.

Retrospective analysis of Braak stage- and APOE4 allele-dependent associations between MR spectroscopy and markers of tau and neurodegeneration in cognitively unimpaired elderly.

PURPOSE: The pathological hallmarks of Alzheimer's disease (AD), amyloid, tau, and associated neurodegeneration, are present in the cortical gray matter (GM) years before symptom onset, and at significantly greater levels in carriers of the apolipoprotein E4 (APOE4) allele. Their respective biomarkers, A/T/N, have been found to correlate with aspects of brain biochemistry, measured with magnetic resonance spectroscopy (MRS), indicating a potential for MRS to augment the A/T/N framework for staging and prediction of AD. Unfortunately, the relationships between MRS and A/T/N biomarkers are unclear, largely due to a lack of studies examining them in the context of the spatial and temporal model of T/N progression. Advanced MRS acquisition and post-processing approaches have enabled us to address this knowledge gap and test the hypotheses, that glutamate-plus-glutamine (Glx) and N-acetyl-aspartate (NAA), metabolites reflecting synaptic and neuronal health, respectively, measured from regions on the Braak stage continuum, correlate with: (i) cerebrospinal fluid (CSF) p-tau181 level (T), and (ii) hippocampal volume or cortical thickness of parietal lobe GM (N). We hypothesized that these correlations will be moderated by Braak stage and APOE4 genotype. METHODS: We conducted a retrospective imaging study of 34 cognitively unimpaired elderly individuals who received APOE4 genotyping and lumbar puncture from pre-existing prospective studies at the NYU Grossman School of Medicine between October 2014 and January 2019. Subjects returned for their imaging exam between April 2018 and February 2020. Metabolites were measured from the left hippocampus (Braak II) using a single-voxel semi-adiabatic localization by adiabatic selective refocusing sequence; and from the bilateral posterior cingulate cortex (PCC; Braak IV), bilateral precuneus (Braak V), and bilateral precentral gyrus (Braak VI) using a multi-voxel echo-planar spectroscopic imaging sequence. Pearson and Spearman correlations were used to examine the relationships between absolute levels of choline, creatine, myo-inositol, Glx, and NAA and CSF p-tau181, and between these metabolites and hippocampal volume or parietal cortical thicknesses. Covariates included age, sex, years of education, Fazekas score, and months between CSF collection and MRI exam. RESULTS: There was a direct correlation between hippocampal Glx and CSF p-tau181 in APOE4 carriers (Pearson's r = 0.76, p = 0.02), but not after adjusting for covariates. In the entire cohort, there was a direct correlation between hippocampal NAA and hippocampal volume (Spearman's r = 0.55, p = 0.001), even after adjusting for age and Fazekas score (Spearman's r = 0.48, p = 0.006). This relationship was observed only in APOE4 carriers (Pearson's r = 0.66, p = 0.017), and was also retained after adjustment (Pearson's r = 0.76, p = 0.008; metabolite-by-carrier interaction p = 0.03). There were no findings in the PCC, nor in the negative control (late Braak stage) regions of the precuneus and precentral gyrus. CONCLUSIONS: Our findings are in line with the spatially- and temporally-resolved Braak staging model of pathological severity in which the hippocampus is affected earlier than the PCC. The correlations, between MRS markers of synaptic and neuronal health and, respectively, T and N pathology, were found exclusively within APOE4 carriers, suggesting a connection with AD pathological change, rather than with normal aging. We therefore conclude that MRS has the potential to augment early A/T/N staging, with the hippocampus serving as a more sensitive MRS target compared to the PCC.

Multifunctional Drug- and AuNRs-Loaded ROS-Responsive Selenium-Containing Polyurethane Nanofibers for Smart Wound Healing.

Elevated levels of ROS, bacterial infection, inflammation, and improper regeneration are the factors that need to be addressed simultaneously for achieving effective wound healing without scar formation. This study focuses on the fabrication of electrospun ROS-responsive selenium-containing polyurethane nanofibers incorporating deferoxamine mesylate (Def), indomethacin (Indo), and gold nanorods (AuNRs) as proangiogenesis, anti-inflammatory, and antibacterial agents for synchronized delivery to a full-thickness wound in vivo. The structure of the fabricated nanofibers was analyzed by various techniques. Toxicity was checked by CCK-8 and hemolytic assays. The efficiency of wound healing in vitro was verified by a transwell assay and cell scratch assay. The wound healing efficiency of the nanofibers was assayed in full-thickness wounds in a rat model. The multifunctional nanofibers had a porous structure, enhanced antioxidation, antibacterial activity, and promoted wound healing. They eradicated TNF-α and IL-6, increased IL-10 expression, and revealed the angiogenic potential by increased expression of HIF-1α, VEGF, and CD31.

Influence of enantiomeric polylysine grafted on gold nanorods on the uptake and inflammatory response of bone marrow-derived macrophages in vitro.

The macrophages take significant roles in homeostasis, phagocytosis of pathogenic organisms, and modulation of host defense and inflammatory processes. In this study, the enantiomeric poly-D-lysine (PDL) and poly-L-lysine (PLL) were conjugated to gold nanorods (AuNRs) to study their influence on the polarization of macrophages. The AuNRs capped with cetyl trimethyl ammonium bromide (CTAB) (AuNRs@CTAB) exhibited larger toxicity to macrophages when their concentration was higher than 50 µg/ml, whereas the AuNRs@PDL and AuNRs@PLL showed neglectable toxicity at the same concentration compared with the control. The AuNRs@PDL and AuNRs@PLL were internalized into the macrophages with a higher value than the AuNRs@CTAB as revealed by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS) characterization. Unlike the grafted PDL/PLL on flat substrates, the AuNRs@PDL and AuNRs@PLL were not able to polarize M0 macrophages to any other phenotype after internalization as confirmed by ELISA, flow cytometry, and fluorescence microscopy analysis. Nonetheless, the expression of M1 phenotype markers was reduced after the internalization of AuNRs@PDL and AuNRs@PLL by M1 macrophages. The assays of ELISA, flow cytometry, and reactive oxygen species levels exhibited decrease in inflammation of the M1 macrophages.

Design and Applications of Cell-Selective Surfaces and Interfaces.

Tissue regeneration involves versatile types of cells. The accumulation and disorganized behaviors of undesired cells impair the natural healing process, leading to uncontrolled immune response, restenosis, and/or fibrosis. Cell-selective surfaces and interfaces can have specific and positive effects on desired types of cells, allowing tissue regeneration with restored structures and functions. This review outlines the importance of surfaces and interfaces of biomaterials with cell-selective properties. The chemical and biological cues including peptides, antibodies, and other molecules, physical cues such as topography and elasticity, and physiological cues referring mainly to interactions between cells-cells and cell-chemokines or cytokines are effective modulators for achieving cell selectivity upon being applied into the design of biomaterials. Cell-selective biomaterials have also shown practical significance in tissue regeneration, in particular for endothelialization, nerve regeneration, capture of stem cells, and regeneration of tissues of multiple structures and functions.

PEG capped methotrexate silver nanoparticles for efficient anticancer activity and biocompatibility.

BACKGROUND: Nanocarriers endow tremendous benefits to the drug delivery systems depending upon the specific properties of either component. These benefits include, increase in the drug blood retention time, reduced efflux, additional toxicity and targeted delivery. Methotrexate (MTX) is clinically used for cancer treatment. Higher dosage of MTX results in hepatic and renal toxicity. In this study methotrexate silver nanoparticles (Ag-MTX) coated with polyethylene glycol (PEG) are synthesized and characterized. Their anticancer activity and biocompatibility is also evaluated. RESULTS: Ag-MTX nanoparticles are synthesized by chemical reduction method. They are characterized by Ultraviolet-Visible Spectroscopy and Fourier Transform Infrared Spectroscopy. Average size of PEG coated Ag-MTX nanoparticles (PEG-Ag-MTX nanoparticles) is 12nm. These particles exhibited improved anticancer activity against MCF-7 cell line. Hemolytic activity of these particles was significantly less than MTX. CONCLUSION: PEG-Ag-MTX nanoparticles are potential nanocarrier of methotrexate which may offer MTX based cancer treatment with reduced side effects. In-vivo investigations should be carried out to explore them in detail.