The correlation between neuropathology levels and cognitive performance in centenarians.

INTRODUCTION: Neuropathological substrates associated with neurodegeneration occur in brains of the oldest old. How does this affect cognitive performance? METHODS: The 100-plus Study is an ongoing longitudinal cohort study of centenarians who self-report to be cognitively healthy; post mortem brain donation is optional. In 85 centenarian brains, we explored the correlations between the levels of 11 neuropathological substrates with ante mortem performance on 12 neuropsychological tests. RESULTS: Levels of neuropathological substrates varied: we observed levels up to Thal-amyloid beta phase 5, Braak-neurofibrillary tangle (NFT) stage V, Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-neuritic plaque score 3, Thal-cerebral amyloid angiopathy stage 3, Tar-DNA binding protein 43 (TDP-43) stage 3, hippocampal sclerosis stage 1, Braak-Lewy bodies stage 6, atherosclerosis stage 3, cerebral infarcts stage 1, and cerebral atrophy stage 2. Granulovacuolar degeneration occurred in all centenarians. Some high performers had the highest neuropathology scores. DISCUSSION: Only Braak-NFT stage and limbic-predominant age-related TDP-43 encephalopathy (LATE) pathology associated significantly with performance across multiple cognitive domains. Of all cognitive tests, the clock-drawing test was particularly sensitive to levels of multiple neuropathologies.

Carriers of the p.P522R variant in PLCγ2 have a slightly more responsive immune system.

BACKGROUND: The rs72824905 single-nucleotide polymorphism in the PLCG2 gene, encoding the p.P522R residue change in Phospholipase C gamma 2 (PLCγ2), associates with protection against several dementia subtypes and with increased likelihood of longevity. Cell lines and animal models indicated that p.P522R is a functional hypermorph. We aimed to confirm this in human circulating peripheral immune cells. METHODS: We compared effects of p.P522R on immune system function between carriers and non-carriers (aged 59-103y), using in-depth immunophenotyping, functional B-cell and myeloid cell assays, and in vivo SARS-CoV-2 vaccination. RESULTS: In line with expectations, p.P522R impacts immune cell function only slightly, but it does so across a wide array of immune cell types. Upon B-cell stimulation, we observed increased PLCγ2 phosphorylation and calcium release, suggesting increased B-cell sensitivity upon antigen recognition. Further, p.P522R-carriers had higher numbers of CD20++CD21-CD24+ naive B cells and IgG1+ memory B cells. In myeloid cells, normalized ROS production was higher upon PLCγ2-dependent stimulation. On classical monocytes, CD33 levels were elevated. Furthermore, carriers expressed lower levels of allergy-related FcεRI on several immune cell subsets. Nevertheless, carriers and non-carriers had similar serological responses to SARS-CoV-2 vaccination. CONCLUSION: The immune system from p.P522R-carriers is slightly more responsive to stimulation than in non-carriers.

Long-term wellbeing and neurocognitive functioning of diffuse low-grade glioma patients and their caregivers: A longitudinal study spanning two decades.

BACKGROUND: While patients with diffuse low-grade glioma (LGG) often survive for years, there is a risk of tumor progression which may impact patients' long-term health-related quality of life (HRQOL) and neurocognitive functioning (NCF). We present a follow-up of LGG patients and their informal caregivers (T3) who took part in our previous HRQOL investigations (T1, M = 7 and T2 M = 13 years after diagnosis). METHODS: Participants completed HRQOL (short form-36 health survey [SF-36]; EORTC-BN20), fatigue (Checklist Individual Strength [CIS]), and depression (Center for Epidemiological Studies-Depression [CES-D]) questionnaires and underwent NCF assessments. T3 scores were compared with matched controls. Changes over time (T1-T2-T3) on group and participant level were assessed. Where available, histology of the initial tumor was revised and immunohistochemical staining for IDH1 R132H mutant protein was performed. RESULTS: Thirty patients and nineteen caregivers participated. Of N = 11 with tissue available, 3 patients had confirmed diffuse LGG. At T3, patients (M = 26 years after diagnosis) had HRQOL and NCF similar to, or better than controls, yet 23.3% and 53.3% scored above the cut-off for depression (≥16 CES-D) and fatigue (≥35 CIS), respectively. Caregivers' HRQOL was similar to controls but reported high rates of fatigue (63.2%). Over time, patients' mental health improved (P < .05). Minimal detectable change in HRQOL over time was observed in individual patients (30% improvement; 23.3% decline; 20% both improvement and decline) with 23.3% remaining stable. NCF remained stable or improved in 82.8% of patients. CONCLUSIONS: While HRQOL and NCF do not appear greatly impacted during long-term survivorship in LGG, depressive symptoms and fatigue are persistent.

Improved Wood-Bond Strengths Using Soy and Canola Flours with pMDI and PAE.

The surprising lack of literature on using the very common wood adhesive polymeric methylenediphenyl diisocyanate (pMDI) with protein adhesives may be because of perceived poor improvement of protein wet strength. Reacting pMDI with the flour (soy or canola) before adding water unexpectedly improves wood bonding compared to adding the pMDI to an aqueous protein slurry. Mixing the liquid pMDI with the oilseed flour produces a free-flowing powder with up to 50% of pMDI to flour by weight. The mixture slowly reacts since the isocyanate band in the infrared spectra remains for several days but diminishes with time. Adding pMDI increases the dry and wet strength of wood bonds using Automated Bonding Evaluation System (ABES) testing and levels off at about 50%. Similarly, adding the polyamidoamine-epichlorohydrin (PAE) cross-linker to the oilseed flour increases dry and wet bond strength, but the effect levels off at about 20% of PAE. However, the combination of these two cross-linkers added to the flours results in greater dry and wet shear strength than either one alone. In addition to tests using ABES (ASTM D 7998), the increase in strengths is also observed-but with a diminished effect-in bonding plywood using the interior plywood strength test ASTM D 906.

Standard Test Method ASTM D 7998-19 for the Cohesive Strength Development of Wood Adhesives.

The properties of cured wood adhesives are difficult to study because of the loss of water and other components to the wood, the influence of wood on the adhesive cure, and the effect of adhesive penetration on the wood interphase; thus, normal testing of a neat adhesive film is generally not useful. Most tests of wood adhesive bond strength are slow, laborious, can be strongly influenced by the wood and do not provide information on the kinetics of cure. Test method ASTM D 7998-19, however, can be used for fast evaluation of the strength of wood bonds. The use of a smooth, uniform, and strong wood surface, like maple face-veneer, and sufficient bonding pressure reduces the adhesion and wood strength effects on bond strength. This method has three main applications. The first is to provide consistent data on bond strength development. The second is to measure the dry and wet strengths of bonded lap shear samples. The third is to better understand the adhesive heat resistance by quickly evaluating thermal sensitivity and distinguishing between thermal softening and thermal degradation.

Reactions of Soy Flour and Soy Protein by Non-Volatile Aldehydes Generation by Specific Oxidation.

Soy protein isolate (SPI) and insoluble soy flour polymeric carbohydrates have been reacted with sodium periodate for the specific oxidation of vicinal -OH groups to investigate the reactions involved in this approach to soy flour adhesives. The reactions have been shown to generate carbohydrate oligomer fractions presenting one, two or multiple aldehyde groups. With the exception of the small molecular weight heptanedial, the smaller molecular weight aldehydes generated from mono- and disaccharides by the same reaction do not appear to form from the insoluble soy flour carbohydrates, or have already reacted. The reaction of periodate with soy protein isolate has been shown to generate some aldehydes too. When the mix of SPI and soy insoluble carbohydrates is treated with periodate, the majority of the observed aldehyde carrying species appear to be higher molecular weight carbohydrate oligomer fractions.

Mechanosensing by ß1 integrin induces angiocrine signals for liver growth and survival.

Angiocrine signals derived from endothelial cells are an important component of intercellular communication and have a key role in organ growth, regeneration and disease1-4. These signals have been identified and studied in multiple organs, including the liver, pancreas, lung, heart, bone, bone marrow, central nervous system, retina and some cancers1-4. Here we use the developing liver as a model organ to study angiocrine signals5,6, and show that the growth rate of the liver correlates both spatially and temporally with blood perfusion to this organ. By manipulating blood flow through the liver vasculature, we demonstrate that vessel perfusion activates ß1 integrin and vascular endothelial growth factor receptor 3 (VEGFR3). Notably, both ß1 integrin and VEGFR3 are strictly required for normal production of hepatocyte growth factor, survival of hepatocytes and liver growth. Ex vivo perfusion of adult mouse liver and in vitro mechanical stretching of human hepatic endothelial cells illustrate that mechanotransduction alone is sufficient to turn on angiocrine signals. When the endothelial cells are mechanically stretched, angiocrine signals trigger in vitro proliferation and survival of primary human hepatocytes. Our findings uncover a signalling pathway in vascular endothelial cells that translates blood perfusion and mechanotransduction into organ growth and maintenance.

Synchrotron-based X-ray fluorescence microscopy in conjunction with nanoindentation to study molecular-scale interactions of phenol-formaldehyde in wood cell walls.

Understanding and controlling molecular-scale interactions between adhesives and wood polymers are critical to accelerate the development of improved adhesives for advanced wood-based materials. The submicrometer resolution of synchrotron-based X-ray fluorescence microscopy (XFM) was found capable of mapping and quantifying infiltration of Br-labeled phenol-formaldehyde (BrPF) into wood cell walls. Cell wall infiltration of five BrPF adhesives with different average molecular weights (MWs) was mapped. Nanoindentation on the same cell walls was performed to assess the effects of BrPF infiltration on cell wall hygromechanical properties. For the same amount of weight uptake, lower MW BrPF adhesives were found to be more effective at decreasing moisture-induced mechanical softening. This greater effectiveness of lower MW phenolic adhesives likely resulted from their ability to more intimately associate with water sorption sites in the wood polymers. Evidence also suggests that a BrPF interpenetrating polymer network (IPN) formed within the wood polymers, which might also decrease moisture sorption by mechanically restraining wood polymers during swelling.