Assessment of Exercise Capacity of Individuals with Long COVID: A Cross-sectional Study.

BACKGROUND: Clinical investigations of long-term effects of coronavirus disease 2019 (COVID-19) are rarely translated to objective findings. OBJECTIVES: To assess the functional capacity of individuals reported on deconditioning that hampered their return to their pre-COVID routine. METHODS: Assessment included the 6-minute walk test (6MWT) and the 30-second sit-to-stand test (30-STST). We compared the expected and observed scores using the Wilcoxon signed-rank test. Predictors of test scores were identified using linear regression models. RESULTS: We included 49 individuals, of whom 38 (77.6%) were recovering from mild COVID-19. Twenty-seven (55.1%) individuals had a 6MWT score lower than 80% of expected. The average 6MWT scores were 129.5 ± 121.2 meters and 12.2 ± 5.0 repeats lower than expected scores, respectively (P < 0.001 for both). The 6MWT score was 107.3 meters lower for individuals with severe COVID-19 (P = 0.013) and rose by 2.7 meters per each 1% increase in the diffusing capacity of carbon monoxide (P = 0.007). The 30-STST score was 3.0 repeats lower for individuals who reported moderate to severe myalgia (P = 0.038). CONCLUSIONS: Individuals with long COVID who report on deconditioning exhibit significantly decreased physical capacity, even following mild acute illness. Risk factors include severe COVID-19 and impaired diffusing capacity or myalgia during recovery.

An application of neighbourhoods in digraphs to the classification of binary dynamics.

A binary state on a graph means an assignment of binary values to its vertices. A time-dependent sequence of binary states is referred to as binary dynamics. We describe a method for the classification of binary dynamics of digraphs, using particular choices of closed neighbourhoods. Our motivation and application comes from neuroscience, where a directed graph is an abstraction of neurons and their connections, and where the simplification of large amounts of data is key to any computation. We present a topological/graph theoretic method for extracting information out of binary dynamics on a graph, based on a selection of a relatively small number of vertices and their neighbourhoods. We consider existing and introduce new real-valued functions on closed neighbourhoods, comparing them by their ability to accurately classify different binary dynamics. We describe a classification algorithm that uses two parameters and sets up a machine learning pipeline. We demonstrate the effectiveness of the method on simulated activity on a digital reconstruction of cortical tissue of a rat, and on a nonbiological random graph with similar density.

Topology of synaptic connectivity constrains neuronal stimulus representation, predicting two complementary coding strategies.

In motor-related brain regions, movement intention has been successfully decoded from in-vivo spike train by isolating a lower-dimension manifold that the high-dimensional spiking activity is constrained to. The mechanism enforcing this constraint remains unclear, although it has been hypothesized to be implemented by the connectivity of the sampled neurons. We test this idea and explore the interactions between local synaptic connectivity and its ability to encode information in a lower dimensional manifold through simulations of a detailed microcircuit model with realistic sources of noise. We confirm that even in isolation such a model can encode the identity of different stimuli in a lower-dimensional space. We then demonstrate that the reliability of the encoding depends on the connectivity between the sampled neurons by specifically sampling populations whose connectivity maximizes certain topological metrics. Finally, we developed an alternative method for determining stimulus identity from the activity of neurons by combining their spike trains with their recurrent connectivity. We found that this method performs better for sampled groups of neurons that perform worse under the classical approach, predicting the possibility of two separate encoding strategies in a single microcircuit.

A Topological Representation of Branching Neuronal Morphologies.

Many biological systems consist of branching structures that exhibit a wide variety of shapes. Our understanding of their systematic roles is hampered from the start by the lack of a fundamental means of standardizing the description of complex branching patterns, such as those of neuronal trees. To solve this problem, we have invented the Topological Morphology Descriptor (TMD), a method for encoding the spatial structure of any tree as a "barcode", a unique topological signature. As opposed to traditional morphometrics, the TMD couples the topology of the branches with their spatial extents by tracking their topological evolution in 3-dimensional space. We prove that neuronal trees, as well as stochastically generated trees, can be accurately categorized based on their TMD profiles. The TMD retains sufficient global and local information to create an unbiased benchmark test for their categorization and is able to quantify and characterize the structural differences between distinct morphological groups. The use of this mathematically rigorous method will advance our understanding of the anatomy and diversity of branching morphologies.

Cliques of Neurons Bound into Cavities Provide a Missing Link between Structure and Function.

The lack of a formal link between neural network structure and its emergent function has hampered our understanding of how the brain processes information. We have now come closer to describing such a link by taking the direction of synaptic transmission into account, constructing graphs of a network that reflect the direction of information flow, and analyzing these directed graphs using algebraic topology. Applying this approach to a local network of neurons in the neocortex revealed a remarkably intricate and previously unseen topology of synaptic connectivity. The synaptic network contains an abundance of cliques of neurons bound into cavities that guide the emergence of correlated activity. In response to stimuli, correlated activity binds synaptically connected neurons into functional cliques and cavities that evolve in a stereotypical sequence toward peak complexity. We propose that the brain processes stimuli by forming increasingly complex functional cliques and cavities.

A new real-time visual assessment method for faulty movement patterns during a jump-landing task.

OBJECTIVE: Determine the interrater reliability of a new real-time assessment of faulty movement patterns during a jump-landing task. DESIGN: Interrater reliability study. SETTING: Human movement laboratory. PARTICIPANTS: 50 healthy females. MAIN OUTCOME MEASURES: Assessment included 6 items which were evaluated from a front and a side view. Two Physical Therapy students used a 9-point scale (0-8) to independently rate the quality of movement as good (0-2), moderate (3-5), or poor (6-8). Interrater reliability was expressed by percent agreement and weighted kappa. RESULTS: One examiner rated the quality of movement of 6 subjects as good, 34 subjects as moderate, and 10 subjects as poor. The second examiner rated the quality of movement of 12 subjects as good, 23 subjects as moderate, and 15 subjects as poor. Percent agreement and weighted kappa (95% confidence interval) were 78% and 0.68 (0.51, 0.85), respectively. CONCLUSIONS: A new real-time assessment of faulty movement patterns during jump-landing demonstrated adequate interrater reliability. Further study is warranted to validate this method against a motion analysis system, as well as to establish its predictive validity for injury.

Cardiac Hypertrophy and Cardiac Cell Death in Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is a prevalent clinical condition affecting 15% of the general population. Cardiorenal syndrome (CRS) type 4 is characterized by an underlying CKD condition leading to impairment of cardiac function and increased risk for major cardiovascular events. To date, the mechanisms leading from CKD to CRS are not completely understood. In particular, it is unclear whether the pathological changes that occur in the heart in the setting of CKD involve enhanced cell death of cardiac cells. OBJECTIVES: To assess whether CKD may mediate loss of cardiac cells by apoptosis. METHODS: We established rat models for CKD, acute myocardial infarction (acute MI), left ventricular dysfunction (LVD), and sham. We measured the cardiac-to-body weight as well as kidney-to-body weight ratios to validate that renal and cardiac hypertrophy occur as part of disease progression to CRS. Cardiac cells were then isolated and the percent of cell death was determined by flow cytometry following staining with annexin-FITC and propidium iodide. In addition, the levels of caspase-3-dependent apoptosis were determined by Western blot analysis using an anti-cleaved caspase-3 antibody. RESULTS: CKD, as well as acute MI and LVD, resulted in significant cardiac hypertrophy. Nevertheless, unlike the increased levels of cell death observed in the acute MI group, in the CKD group, cardiac hypertrophy was not associated with induction of cell death of cardiac cells. Caspase-3 activity was even slightly reduced compared to sham-operated controls. CONCLUSIONS: Our data show that while CKD induces pathological changes in the heart, it does not induce cardiac cell death.

The effects of vital dyes on retinal pigment epithelium cells in oxidative stress.

PURPOSE: To determine the effect of the most commonly used vital dyes in vitrectomy [trypan blue at 0.15% concentration and indocyanine green (ICG) at 0.5% concentration] on the viability of human retinal pigment epithelium (RPE) cell lines (ARPE-19) exposed to oxidative stress. METHODS: ARPE-19 cells unexposed or exposed to oxidative stress (hypoxic chamber) were treated for 1 min with one of the dyes. RPE proliferation was measured by (3)H-thymidine incorporation, adhesion by ability to adhere to fibronectin, and safety by annexin V staining. RESULTS: Proliferation: The dyes affected the proliferation of RPE cells differently under non-hypoxic and hypoxic conditions (p = 0.001). In non-hypoxic conditions, there was no statistically significant difference between the proliferation of the treated (both dyes) and untreated RPE cells (p = 0.279). Under hypoxia, both dyes significantly suppressed proliferation, more so with ICG (p = 0.001). Adhesion: The dyes affected adhesion differently under non-hypoxic and hypoxic conditions (p = 0.04). In non-hypoxic conditions, both increased the adhesive properties of RPE cells to fibronectin, ICG more than trypan blue (p = 0.001). Under hypoxia, both dyes suppressed adhesion, with no statistically significant difference between treated and non-treated RPE cells. Apoptosis: Both dyes increased early apoptosis of RPE cells compared with no treatment (p = 0.001), ICG more than trypan blue. Hypoxia increased the apoptosis of both dyes compared to non-hypoxic conditions (p = 0.02). CONCLUSIONS: In hypoxic conditions, both dyes showed an inhibition of RPE adhesion to fibronectin and proliferation capacity and an increase in early apoptosis compared with non-hypoxic conditions. Apoptosis was greater in ICG-treated RPE cells than in trypan blue-treated cells.

Viruses selectively mutate their CD8+ T-cell epitopes--a large-scale immunomic analysis.

MOTIVATION: Viruses employ various means to evade immune detection. One common evasion strategy is the removal of CD8+cytotoxic T-lymphocyte epitopes. We here use a combination of multiple bioinformatic tools and large amount of genomic data to compute the epitope repertoire presented by over 1300 viruses in many HLA alleles. We define the 'Size of Immune Repertoire score', which represents the ratio between the epitope density within a protein and the expected density. This score is used to study viral immune evasion. RESULTS: We show that viral proteins in general have a higher epitope density than human proteins. This difference is due to a good fit of the human MHC molecules to the typical amino-acid usage of viruses. Among different viruses, viruses infecting humans present less epitopes than non-human viruses. This selection is not at the amino-acid usage level, but through the removal of specific epitopes. Within a single virus, not all proteins express the same epitopes density. Proteins expressed early in the viral life cycle have a lower epitope density than late proteins. Such a difference is not observed in non-human viruses. The removal of early epitopes and the targeting of the cellular immune response to late viral proteins, allow the virus a time interval to propagate before its host cells are destroyed by T cells.

Atmospheric modulation transfer function in the infrared.

In high-resolution ultranarrow field-of-view thermal imagers, image quality over relatively long path lengths is typically limited by atmospheric degradation, especially atmospheric blur. We report our results and analyses of infrared images from two sites, Fort A. P. Hill and Aberdeen Proving Ground. The images are influenced by the various atmospheric phenomena: scattering, absorption, and turbulence. A series of experiments with high-resolution equipment in both the 3-5- and 8-13-microm regions at the two locations indicate that, as in the visible, image quality is limited much more by atmosphere than by the instrumentation for ranges even of the order of only a few kilometers. For paths close to the ground, turbulence is more dominant, whereas for paths involving higher average elevation, aerosol modulation transfer function (MTF) is dominant. As wavelength increases, turbulence MTF also increases, thus permitting aerosol MTF to become more dominant. A critical role in aerosol MTF in the thermal infrared is attributed to absorption, which noticeably decreases atmospheric transmission much more than in the visible, thereby reducing high-spatial-frequency aerosol MTF. These measurements indicate that atmospheric MTF should be a basic component in imaging system design and analysis even in the infrared, especially as higher-resolution hardware becomes available.