Multispectral oximetry of murine tendon microvasculature with inflammation

We report a novel multispectral imaging technique for localised measurement of vascular oxygen saturation (SO2) in vivo. Annular back-illumination is generated using a Schwarzchild-design reflective objective. Analysis of multispectral data is performed using a calibration-free oximetry algorithm. This technique is applied to oximetry in mice to measure SO2 in microvasculature supplying inflamed tendon tissue in the hind leg. Average SO2 for controls was 94.8 ± 7.0 % (N = 6), and 84.0 ± 13.5 % for mice with inflamed tendon tissue (N = 6). We believe this to be the first localised measurement of hypoxia in tendon microvasculature due to inflammation. Quantification of localised SO2 is important for the study of inflammatory diseases such as rheumatoid arthritis, where hypoxia is thought to play a role in pathogenesis

Minimally Invasive Optical Biopsy for Oximetry

The study of localised oxygen saturation in blood vessels can shed light on the etiology and progression of many diseases with which hypoxia is associated. For example, hypoxia in the tendon has been linked to early stages of rheumatoid arthritis, an auto-immune inflammatory disease. Vascular oximetry of deep tissue presents significant challenges as vessels are not optically accessible. In this paper, we present a novel multispectral imaging technique for vascular oximetry, and recent developments made towards its adaptation for minimally invasive imaging. We present proof-of-concept of the system and illumination scheme as well as the analysis technique. We present results of a validation study performed in vivo on mice with acutely inflamed tendons. Adaptation of the technique for minimally invasive microendoscopy is also presented, along with preliminary results of minimally invasive ex vivo vascular oximetry

An Analysis of Poverty Convergence: Evidence from Pennsylvania Counties

This paper extends applications of unconditional and conditional β-convergence and σ-convergence analysis to poverty rates in a panel data sample of Pennsylvania counties during the period 1990-2019. Spatial structural breaks between rural and urban counties in Pennsylvania plus the possibility that Philadelphia County is an outlier are acknowledged to avoid spurious inferences. The findings support the existence of unconditional β-convergence in the pooled, urban, and rural samples with non-metropolitan areas exhibiting the greatest convergence. However, the largest conditional β-convergence is observed for urban counties, and this outcome is robust to the exclusion of Philadelphia County. Graphical evidence evinces a greater degree of σ-divergence in rural areas relative to the pooled and urban samples with metropolitan areas exhibiting neither convergence nor divergence in the absence of Philadelphia County. Statistical evidence based on ADF and DF-GLS tests reveals the presence of σ-divergence in the pooled and rural samples but weaker findings for the urban counties. Panel data tests for unit roots indicate σ-convergence for the full and rural samples but mixed results for the urban sample depending upon the test employed and whether Philadelphia County is included or not. The findings indicate that further investigation of tailored policy responses to poverty in different geographic areas within the same state is warranted

Antigen depot is not required for alum adjuvanticity

Alum adjuvants have been in continuous clinical use for more than 80 yr. While the prevailing theory has been that depot formation and the associated slow release of antigen and/or inflammation are responsible for alum enhancement of antigen presentation and subsequent T- and B-cell responses, this has never been formally proven. To examine antigen persistence, we used the chimeric fluorescent protein EαGFP, which allows assessment of antigen presentation in situ, using the Y-Ae antibody. We demonstrate that alum and/or CpG adjuvants induced similar uptake of antigen, and in all cases, GFP signal did not persist beyond 24 h in draining lymph node antigen-presenting cells. Antigen presentation was first detectable on B cells within 6–12 h of antigen administration, followed by conventional dendritic cells (DCs) at 12–24 h, then finally plasmacytoid DCs at 48 h or later. Again, alum and/or CpG adjuvants did not have an effect on the magnitude or sequence of this response; furthermore, they induced similar antigen-specific T-cell activation in vivo. Notably, removal of the injection site and associated alum depot, as early as 2 h after administration, had no appreciable effect on antigen-specific T- and B-cell responses. This study clearly rules out a role for depot formation in alum adjuvant activity

A cryptic cycle in haematopoietic niches promotes initiation of malaria transmission and evasion of chemotherapy

Blood stage human malaria parasites may exploit erythropoietic tissue niches and colonise erythroid progenitors; however, the precise influence of the erythropoietic environment on fundamental parasite biology remains unknown. Here we use quantitative approaches to enumerate Plasmodium infected erythropoietic precursor cells using an in vivo rodent model of Plasmodium berghei. We show that parasitised early reticulocytes (ER) in the major sites of haematopoiesis establish a cryptic asexual cycle. Moreover, this cycle is characterised by early preferential commitment to gametocytogenesis, which occurs in sufficient numbers to generate almost all of the initial population of circulating, mature gametocytes. In addition, we show that P. berghei is less sensitive to artemisinin in splenic ER than in blood, which suggests that haematopoietic tissues may enable origins of recrudescent infection and emerging resistance to antimalarials. Continuous propagation in these sites may also provide a mechanism for continuous transmission and infection in malaria endemic regions

Images in cardiovascular medicine : multiphoton microscopy for three-dimensional imaging of lymphocyte recruitment into apolipoprotein-E-deficient mouse carotid artery

Two recent elegant studies have shown that in apolipoprotein-E– deficient mice, the lamina adventitia is a major site of arterial wall inflammation associated with lymphocyte infiltration into atherosclerotic arteries and with formation of adventitial lymphoid-like tissues.1,2 These results suggest that lymphocyte responses in the lamina adventitia may play a crucial role in atherosclerosis development.1,

Tau and atrophy: domain-specific relationships with cognition.

BackgroundLate-onset Alzheimer's disease (AD) is characterized by primary memory impairment, which then progresses towards severe deficits across cognitive domains. Here, we report how performance in cognitive domains relates to patterns of tau deposition and cortical thickness.MethodsWe analyzed data from 131 amyloid-β positive participants (55 cognitively normal, 46 mild cognitive impairment, 30 AD) of the Alzheimer's Disease Neuroimaging Initiative who underwent magnetic resonance imaging (MRI), flortaucipir (FTP) positron emission tomography, and neuropsychological testing. Surface-based vertex-wise and region-of-interest analyses were conducted between FTP and cognitive test scores, and between cortical thickness and cognitive test scores.ResultsFTP and thickness were differentially related to cognitive performance in several domains. FTP-cognition associations were more widespread than thickness-cognition associations. Further, FTP-cognition patterns reflected cortical systems that underlie different aspects of cognition.ConclusionsOur findings indicate that AD-related decline in domain-specific cognitive performance reflects underlying progression of tau and atrophy into associated brain circuits. They also suggest that tau-PET may have better sensitivity to this decline than MRI-derived measures of cortical thickness

Women can bear a bigger burden: ante- and post-mortem evidence for reserve in the face of tau.

In this study, we aimed to assess whether women are able to withstand more tau before exhibiting verbal memory impairment. Using data from 121 amyloid-β-positive Alzheimer's Disease Neuroimaging Initiative participants, we fit a linear model with Rey Auditory Verbal Learning Test score as the response variable and tau-PET standard uptake value ratio as the predictor and took the residuals as an estimate of verbal memory reserve for each subject. Women demonstrated higher reserve (i.e. residuals), whether the Learning (t = 2.78, P = 0.006) or Delay (t = 2.14, P = 0.03) score from the Rey Auditory Verbal Learning Test was used as a measure of verbal memory ability. To validate these findings, we examined 662 National Alzheimer's Coordinating Center participants with a C2/C3 score (Consortium to Establish a Registry for Alzheimer's Disease) at autopsy. We stratified our National Alzheimer's Coordinating Center sample into Braak 1/2, Braak 3/4 and Braak 5/6 subgroups. Within each subgroup, we compared Logical Memory scores between men and women. Men had worse verbal memory scores within the Braak 1/2 (Logical Memory Immediate: β = -5.960 ± 1.517, P < 0.001, Logical Memory Delay: β = -5.703 ± 1.677, P = 0.002) and Braak 3/4 (Logical Memory Immediate: β = -2.900 ± 0.938, P = 0.002, Logical Memory Delay: β = -2.672 ± 0.955, P = 0.006) subgroups. There were no sex differences in Logical Memory performance within the Braak 5/6 subgroup (Logical Memory Immediate: β = -0.314 ± 0.328, P = 0.34, Logical Memory Delay: β = -0.195 ± 0.287, P = 0.50). Taken together, our results point to a sex-related verbal memory reserve

Definition of Metabolic Syndrome: Report of the National Heart, Lunch, and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition

https://www.ahajournals.org/doi/pdf/10.1161/01.atv.0000111245.75752.c

Inquiring Decision Systems: A Churchmanian Approach to Ethical Decision Making

Many business organizations seem to be doing everything but making ethical organizational decisions these days. In stark contrast, social enterprises are organizations that operate as businesses but are altruistic, humanitarian, and seek the goal of creating social value in effective, efficient and ethical ways. This paper applies principles of social enterprises to develop a multi-perspective framework for ethical business decision-making within a philosophical context provided by C. West Churchman’s inquiring systems in organizations