A preliminary study about treg cells phenotypic alteration

Las células T reguladoras son una subpoblación de los linfocitos T CD4+ de gran importancia en el establecimiento y mantenimiento de la tolerancia y la homeostasis del sistema inmune. Muchos estudios han analizado la frecuencia de las Treg en pacientes infectados por VIH. Sin embargo, los resultados no son concluyentes y existe una gran controversia sobre el papel que juegan las Treg en el curso de la infección. Recientemente se ha demostrado que el VIH puede infectar las células Treg. Trabajos previos de nuestro grupo demuestran que las Treg son susceptibles de infección por el VIH disminuyendo la expresión del Foxp3 en las células infectadas. Este fenómeno produce una alteración en la capacidad supresora de las células Treg. El objetivo de éste estudio es corroborar dicho comportamiento in vivo y determinar el fenotipo de las Treg en pacientes infectados por VIH. Los resultados preliminares indican que efectivamente la frecuencia de células Foxp3+ es inferior en los pacientes infectados por VIH que en los individuos sanos. El estudio sigue en curso para recopilar un número suficiente de muestras que permitan confirmar estos resultados. Este estudio permitirá conocer mejor el papel de las Treg en el curso de la infección por VIHRegulatory T cells (Treg) are a subpopulation of CD4+ T cells that play a crucial role in establishing and maintaining self-tolerance and immune homeostasis. Many studies have explored the frequency of Treg in HIV infected patients. However, there are controversial findings about the role of these cells in the HIV infection. Nowadays, different studies have showed that Treg cells are susceptible to the HIV infection. Our in vitro data has showed that HIV infects Treg and produces a downregulation of Foxp3 expression. This phenomenon also leads Treg cells to a loss of their immune suppressive capacity. The aim of this study is to corroborate if this behavior also occurs in vivo and determine the Treg phenotype in HIVinfected patients. Preliminary results indicate that frequency of Foxp3+ cells is lower in HIVinfected patients than in healthy volunteers. At present, we are recovering enough number of samples to confirm these results. A better understanding of these cells could serve for the effective exploitation of their suppressive functions for clinical benefit

Sustainable sugarcane vinasse biorefinement for trans-aconitic acid-based biopolymer synthesis and bioenergy generation

This study aimed at developing a multiproduct biorefinery scheme for vinase valorization. It involved the extraction of trans-aconitic acid, its transformation into biopolymers using microwave irradiation and the use of the raffinated-vinasse for biogas production. Each technology was assessed individually, followed by a process integration at bench scale, from which a mass balance was calculated, supporting the feasibility of the approach. As a renewable source derived from a residue, these bioproducts can replace crude-oil-based materials in various chemical industrial processes; however, a detailed techno-economic and life-cycle analysis are required to defined the sustainability of the process

Malarial Hemozoin Activates the NLRP3 Inflammasome through Lyn and Syk Kinases

The intraerythrocytic parasite Plasmodium—the causative agent of malaria—produces an inorganic crystal called hemozoin (Hz) during the heme detoxification process, which is released into the circulation during erythrocyte lysis. Hz is rapidly ingested by phagocytes and induces the production of several pro-inflammatory mediators such as interleukin-1β (IL-1β). However, the mechanism regulating Hz recognition and IL-1β maturation has not been identified. Here, we show that Hz induces IL-1β production. Using knockout mice, we showed that Hz-induced IL-1β and inflammation are dependent on NOD-like receptor containing pyrin domain 3 (NLRP3), ASC and caspase-1, but not NLRC4 (NLR containing CARD domain). Furthermore, the absence of NLRP3 or IL-1β augmented survival to malaria caused by P. chabaudi adami DS. Although much has been discovered regarding the NLRP3 inflammasome induction, the mechanism whereby this intracellular multimolecular complex is activated remains unclear. We further demonstrate, using pharmacological and genetic intervention, that the tyrosine kinases Syk and Lyn play a critical role in activation of this inflammasome. These findings not only identify one way by which the immune system is alerted to malarial infection but also are one of the first to suggest a role for tyrosine kinase signaling pathways in regulation of the NLRP3 inflammasome

Community peer-led falls prevention presentations: What do the experts suggest?

Falls among older adults are a major problem. Despite considerable progress in falls prevention research, older adults often show low motivation to engage in recommended preventive strategies. Peer-led falls prevention education for older adults may have potential for bridging the research evidence-practice gap, thereby promoting the uptake of falls prevention strategies. We evaluated peer educators’ presentations of falls prevention education to community-dwelling older adults in regard to established criteria that were consistent with adult learning principles, the framework of health behaviour change, falls prevention guidelines, and recommendations for providing falls prevention information. We conducted a within-stage mixed model study using purposive and snowball sampling techniques to recruit 10 experts to evaluate video recordings of the delivery of three peer-led falls prevention presentations. Each expert viewed three videos and rated them using a questionnaire containing both open-ended and closed items. There was a good level of expert agreement across the questionnaire domains. Though the experts rated some aspects of the presentations highly, they thought that the presentations were mainly didactic in delivery, not consistently personally relevant to the older adult audience, and did not encourage older adults to engage in the preventive strategies that were presented. Based on the experts’ findings, we developed five key themes and recommendations for the effective delivery of peer led falls prevention presentations. These included recommending that peer educators share falls prevention messages in a more interactive and experiential manner and that uptake of strategies should be facilitated by encouraging the older adults to develop a personalised action plan. Findings suggest that if peer-led falls prevention presentations capitalise on older adults’ capability, opportunity, and motivation, the older adults may be more receptive to take up falls prevention messages

Motion in classical field theories and the foundations of the self-force problem

This article serves as a pedagogical introduction to the problem of motion in classical field theories. The primary focus is on self-interaction: How does an object's own field affect its motion? General laws governing the self-force and self-torque are derived using simple, non-perturbative arguments. The relevant concepts are developed gradually by considering motion in a series of increasingly complicated theories. Newtonian gravity is discussed first, then Klein-Gordon theory, electromagnetism, and finally general relativity. Linear and angular momenta as well as centers of mass are defined in each of these cases. Multipole expansions for the force and torque are then derived to all orders for arbitrarily self-interacting extended objects. These expansions are found to be structurally identical to the laws of motion satisfied by extended test bodies, except that all relevant fields are replaced by effective versions which exclude the self-fields in a particular sense. Regularization methods traditionally associated with self-interacting point particles arise as straightforward perturbative limits of these (more fundamental) results. Additionally, generic mechanisms are discussed which dynamically shift --- i.e., renormalize --- the apparent multipole moments associated with self-interacting extended bodies. Although this is primarily a synthesis of earlier work, several new results and interpretations are included as well.Comment: 68 pages, 1 figur

What are the consequences of combining nuclear and mitochondrial data for phylogenetic analysis? Lessons from Plethodon salamanders and 13 other vertebrate clades

<p>Abstract</p> <p>Background</p> <p>The use of mitochondrial DNA data in phylogenetics is controversial, yet studies that combine mitochondrial and nuclear DNA data (mtDNA and nucDNA) to estimate phylogeny are common, especially in vertebrates. Surprisingly, the consequences of combining these data types are largely unexplored, and many fundamental questions remain unaddressed in the literature. For example, how much do trees from mtDNA and nucDNA differ? How are topological conflicts between these data types typically resolved in the combined-data tree? What determines whether a node will be resolved in favor of mtDNA or nucDNA, and are there any generalities that can be made regarding resolution of mtDNA-nucDNA conflicts in combined-data trees? Here, we address these and related questions using new and published nucDNA and mtDNA data for <it>Plethodon </it>salamanders and published data from 13 other vertebrate clades (including fish, frogs, lizards, birds, turtles, and mammals).</p> <p>Results</p> <p>We find widespread discordance between trees from mtDNA and nucDNA (30-70% of nodes disagree per clade), but this discordance is typically not strongly supported. Despite often having larger numbers of variable characters, mtDNA data do not typically dominate combined-data analyses, and combined-data trees often share more nodes with trees from nucDNA alone. There is no relationship between the proportion of nodes shared between combined-data and mtDNA trees and relative numbers of variable characters or levels of homoplasy in the mtDNA and nucDNA data sets. Congruence between trees from mtDNA and nucDNA is higher on branches that are longer and deeper in the combined-data tree, but whether a conflicting node will be resolved in favor mtDNA or nucDNA is unrelated to branch length. Conflicts that are resolved in favor of nucDNA tend to occur at deeper nodes in the combined-data tree. In contrast to these overall trends, we find that <it>Plethodon </it>have an unusually large number of strongly supported conflicts between data types, which are generally resolved in favor of mtDNA in the combined-data tree (despite the large number of nuclear loci sampled).</p> <p>Conclusions</p> <p>Overall, our results from 14 vertebrate clades show that combined-data analyses are not necessarily dominated by the more variable mtDNA data sets. However, given cases like <it>Plethodon</it>, there is also the need for routine checking of incongruence between mtDNA and nucDNA data and its impacts on combined-data analyses.</p

Socioeconomic Status Is Not Related with Facial Fluctuating Asymmetry: Evidence from Latin-American Populations

The expression of facial asymmetries has been recurrently related with poverty and/or disadvantaged socioeconomic status. Departing from the developmental instability theory, previous approaches attempted to test the statistical relationship between the stress experienced by individuals grown in poor conditions and an increase in facial and corporal asymmetry. Here we aim to further evaluate such hypothesis on a large sample of admixed Latin Americans individuals by exploring if low socioeconomic status individuals tend to exhibit greater facial fluctuating asymmetry values. To do so, we implement Procrustes analysis of variance and Hierarchical Linear Modelling (HLM) to estimate potential associations between facial fluctuating asymmetry values and socioeconomic status. We report significant relationships between facial fluctuating asymmetry values and age, sex, and genetic ancestry, while socioeconomic status failed to exhibit any strong statistical relationship with facial asymmetry. These results are persistent after the effect of heterozygosity (a proxy for genetic ancestry) is controlled in the model. Our results indicate that, at least on the studied sample, there is no relationship between socioeconomic stress (as intended as low socioeconomic status) and facial asymmetries

Electrochemically synthesized polymers in molecular imprinting for chemical sensing

This critical review describes a class of polymers prepared by electrochemical polymerization that employs the concept of molecular imprinting for chemical sensing. The principal focus is on both conducting and nonconducting polymers prepared by electropolymerization of electroactive functional monomers, such as pristine and derivatized pyrrole, aminophenylboronic acid, thiophene, porphyrin, aniline, phenylenediamine, phenol, and thiophenol. A critical evaluation of the literature on electrosynthesized molecularly imprinted polymers (MIPs) applied as recognition elements of chemical sensors is presented. The aim of this review is to highlight recent achievements in analytical applications of these MIPs, including present strategies of determination of different analytes as well as identification and solutions for problems encountered

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference