Disentangling astroglial physiology with a realistic cell model in silico

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we systematically incorporate multi-scale, tri-dimensional astroglial architecture into a realistic multi-compartmental cell model, which we constrain by empirical tests and integrate into the NEURON computational biophysical environment. This approach is implemented as a flexible astrocyte-model builder ASTRO. As a proof-of-concept, we explore an in silico astrocyte to evaluate basic cell physiology features inaccessible experimentally. Our simulations suggest that currents generated by glutamate transporters or K+ channels have negligible distant effects on membrane voltage and that individual astrocytes can successfully handle extracellular K+ hotspots. We show how intracellular Ca2+ buffers affect Ca2+ waves and why the classical Ca2+ sparks-and-puffs mechanism is theoretically compatible with common readouts of astroglial Ca2+ imaging

Hybrid Equation/Agent-Based Model of Ischemia-Induced Hyperemia and Pressure Ulcer Formation Predicts Greater Propensity to Ulcerate in Subjects with Spinal Cord Injury

Pressure ulcers are costly and life-threatening complications for people with spinal cord injury (SCI). People with SCI also exhibit differential blood flow properties in non-ulcerated skin. We hypothesized that a computer simulation of the pressure ulcer formation process, informed by data regarding skin blood flow and reactive hyperemia in response to pressure, could provide insights into the pathogenesis and effective treatment of post-SCI pressure ulcers. Agent-Based Models (ABM) are useful in settings such as pressure ulcers, in which spatial realism is important. Ordinary Differential Equation-based (ODE) models are useful when modeling physiological phenomena such as reactive hyperemia. Accordingly, we constructed a hybrid model that combines ODEs related to blood flow along with an ABM of skin injury, inflammation, and ulcer formation. The relationship between pressure and the course of ulcer formation, as well as several other important characteristic patterns of pressure ulcer formation, was demonstrated in this model. The ODE portion of this model was calibrated to data related to blood flow following experimental pressure responses in non-injured human subjects or to data from people with SCI. This model predicted a higher propensity to form ulcers in response to pressure in people with SCI vs. non-injured control subjects, and thus may serve as novel diagnostic platform for post-SCI ulcer formation. © 2013 Solovyev et al

CoVITEST: A Fast and Reliable Method to Monitor Anti-SARS-CoV-2 Specific T Cells From Whole Blood

Cellular and humoral immune responses are essential for COVID-19 recovery and protection against SARS-CoV-2 reinfection. To date, the evaluation of SARS-CoV-2 immune protection has mainly focused on antibody detection, generally disregarding the cellular response, or placing it in a secondary position. This phenomenon may be explained by the complex nature of the assays needed to analyze cellular immunity compared with the technically simple and automated detection of antibodies. Nevertheless, a large body of evidence supports the relevance of the T cell's role in protection against SARS-CoV-2, especially in vulnerable individuals with a weakened immune system (such as the population over 65 and patients with immunodeficiencies). Here we propose to use CoVITEST (Covid19 anti-Viral Immunity based on T cells for Evaluation in a Simple Test), a fast, affordable and accessible in-house assay that, together with a diagnostic matrix, allows us to determine those patients who might be protected with SARS-CoV-2-reactive T cells. The method was established using healthy SARS-CoV-2-naïve donors pre- and post-vaccination (n=30), and further validated with convalescent COVID-19 donors (n=51) in a side-by-side comparison with the gold standard IFN-? ELISpot. We demonstrated that our CoVITEST presented reliable and comparable results to those obtained with the ELISpot technique in a considerably shorter time (less than 8 hours). In conclusion, we present a simple but reliable assay to determine cellular immunity against SARS-CoV-2 that can be used routinely during this pandemic to monitor the immune status in vulnerable patients and thereby adjust their therapeutic approaches. This method might indeed help to optimize and improve decision-making protocols for re-vaccination against SARS-CoV-2, at least for some population subsets.Copyright © 2022 Egri, Olivé, Hernández-Rodríguez, Castro, De Guzman, Heredia, Segura, Fernandez, de Moner, Torradeflot, Ballús, Martinez, Vazquez, Costa, Dobaño, Mazza, Mazzotti, Pascal, Juan, González-Navarro and Calderón

How acceptable are antiretrovirals for the prevention of sexually transmitted HIV? A review of research on the acceptability of oral pre-exposure prophylaxis and treatment as prevention

Recent research has demonstrated how antiretrovirals (ARVs) could be effective in the prevention of sexually transmitted HIV. We review research on the acceptability of oral pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) for HIV prevention amongst potential users. We consider with whom, where and in what context this research has been conducted, how acceptability has been approached, and what research gaps remain. Findings from 33 studies show a lack of TasP research, PrEP studies which have focused largely on men who have sex with men (MSM) in a US context, and varied measures of acceptability. In order to identify when, where and for whom PrEP and TasP would be most appropriate and effective, research is needed in five areas: acceptability of TasP to people living with HIV; motivation for PrEP use and adherence; current perceptions and management of risk; the impact of broader social and structural factors; and consistent definition and operationalisation of acceptability which moves beyond adherence

Meanings given to algebraic symbolism in problem posing

Some errors in the learning of algebra suggest students have difficulties giving meaning to algebraic symbolism. In this paper, we use problem posing in order to analyze the students’ capacity to assign meaning to algebraic symbolism and the difficulties that students encounter in this process depending on the characteristics of the algebraic statements given. We designed a written questionnaire composed of eight closed algebraic statements expressed symbolically, which was administered to 55 students who had finished their compulsory education and that had some previous experience in problem posing. In our analysis of the data, we examine both syntactic and semantic structures of the problem posed. We note that in most cases students posed problems with syntactic structures different to those given. They did not include computations within variables, and changed the kinds of relationships connecting variables. Students easily posed problems for statements with additive structures. Other differences in the type of problems posed depend on the characteristics of the given statements

The Rise of Cohabitation in the Southern Cone

This chapter analyses the increase in cohabitation in the Southern Cone (Argentina, Chile and Uruguay) and attempts to determine the extent to which consensual unions and marriages have similar traits or differ in the context of the cohabitation boom (Esteve et al. 2012). The first section of the chapter reviews the historical context of cohabitation in the Southern Cone. The second section uses census and survey data to analyse the trends in conjugal union formation in the three countries during the last 40 years. We analyse the patterns of both childbearing and union formation, as well as the differences between marriage and cohabitation based on educational attainment, labour market participation and household structure. The purpose of this analysis is to better understand whether the behaviour of married and cohabiting women with different characteristics are converging or diverging over time and tentatively, whether more egalitarian gender relationships are emerging in both types of conjugal unions

In the eye of the beholder: Eye-tracking assessment of social information processing in aggressive behavior

# The Author(s) 2009. This article is published with open access at Springerlink.com Abstract Acording to social information processing theories, aggressive children are hypersensitive to cues of hostility and threat in other people’s behavior. However, even though there is ample evidence that aggressive children over-interpret others ’ behaviors as hostile, it is unclear whether this hostile attribution tendency does actually result from overattending to hostile and threatening cues. Since encoding is posited to consist of rapid automatic processes, it is hard to assess with the selfreport measures that have been used so far. Therefore, we used a novel approach to investigate visual encoding of social information. The eye movements of thirty 10–13 year old children with lower levels and thirty children with higher levels of aggressive behavior were monitored in real time with an eyetracker, as the children viewed ten different cartoon series of ambiguous provocation situations. In addition, participants answered questions concerning encoding and interpretation. Aggressive children did not attend more to hostile cues, nor attend less to non-hostile cues than non-aggressive children. Contrary, aggressive children looked longer at non-hostile cues, but nonetheless attributed more hostile intent than their non-aggressive peers. These findings contradict the traditional bottom-up processing hypotheses that aggressive behavior would be related with failure to attend to non-hostile cues. The findings seem best explained by topdown information processing, where aggressive children’s pre-existing hostile intent schemata (1) direct attention towards schema inconsistent nonhostile cues, (2) prevent further processing and recall of such schema-inconsistent information, and (3) lead to hostil

Community-based environmental management for malaria control: evidence from a small-scale intervention in Dar es Salaam, Tanzania

Historically, environmental management has brought important achievements in malaria control and overall improvements of health conditions. Currently, however, implementation is often considered not to be cost-effective. A community-based environmental management for malaria control was conducted in Dar es Salaam between 2005 and 2007. After community sensitization, two drains were cleaned followed by maintenance. This paper assessed the impact of the intervention on community awareness, prevalence of malaria infection, and Anopheles larval presence in drains. A survey was conducted in neighbourhoods adjacent to cleaned drains; for comparison, neighbourhoods adjacent to two drains treated with larvicides and two drains under no intervention were also surveyed. Data routinely collected by the Urban Malaria Control Programme were also used. Diverse impacts were evaluated through comparison of means, odds ratios (OR), logistic regression, and time trends calculated by moving averages. Individual awareness of health risks and intervention goals were significantly higher among sensitized neighbourhoods. A reduction in the odds of malaria infection during the post-cleaning period in intervention neighbourhoods was observed when compared to the pre-cleaning period (OR = 0.12, 95% CI 0.05-0.3, p < 0.001). During the post-cleaning period, a higher risk of infection (OR = 1.7, 95% CI 1.1-2.4, p = 0.0069) was observed in neighbourhoods under no intervention compared to intervention ones. Eighteen months after the initial cleaning, one of the drains was still clean due to continued maintenance efforts (it contained no waste materials and the water was flowing at normal velocity). A three-month moving average of the percentage of water habitats in that drain containing pupae and/or Anopheles larvae indicated a decline in larval density. In the other drain, lack of proper resources and local commitment limited success. Although environmental management was historically coordinated by authoritarian/colonial regimes or by industries/corporations, its successful implementation as part of an integrated vector management framework for malaria control under democratic governments can be possible if four conditions are observed: political will and commitment, community sensitization and participation, provision of financial resources for initial cleaning and structural repairs, and inter-sectoral collaboration. Such effort not only is expected to reduce malaria transmission, but has the potential to empower communities, improve health and environmental conditions, and ultimately contribute to poverty alleviation and sustainable development