540 research outputs found
Biphasic toxicodynamic features of some antimicrobial agents on microbial growth: a dynamic mathematical model and its implications on hormesis
<p>Abstract</p> <p>Background</p> <p>In the present work, we describe a group of anomalous dose-response (DR) profiles and develop a dynamic model that is able to explain them. Responses were obtained from conventional assays of three antimicrobial agents (nisin, pediocin and phenol) against two microorganisms (<it>Carnobacterium piscicola </it>and <it>Leuconostoc mesenteroides</it>).</p> <p>Results</p> <p>Some of these anomalous profiles show biphasic trends which are usually attributed to hormetic responses. But they can also be explained as the result of the time-course of the response from a microbial population with a bimodal distribution of sensitivity to an effector, and there is evidence suggesting this last origin. In light of interest in the hormetic phenomenology and the possibility of confusing it with other phenomena, especially in the bioassay of complex materials we try to define some criteria which allow us to distinguish between <it>sensu stricto </it>hormesis and biphasic responses due to other causes. Finally, we discuss some problems concerning the metric of the dose in connection with the exposure time, and we make a cautionary suggestion about the use of bacteriocins as antimicrobial agents.</p> <p>Conclusions</p> <p>The mathematical model proposed, which combines the basis of DR theory with microbial growth kinetics, can generate and explain all types of anomalous experimental profiles. These profiles could also be described in a simpler way by means of bisigmoidal equations. Such equations could be successfully used in a microbiology and toxicology context to discriminate between hormesis and other biphasic phenomena.</p
Utility of Gene Panels for the Diagnosis of Inborn Errors of Metabolism in a Metabolic Reference Center
Next-generation sequencing (NGS) technologies have been proposed as a first-line test for the diagnosis of inborn errors of metabolism (IEM), a group of genetically heterogeneous disorders with overlapping or nonspecific phenotypes. Over a 3-year period, we prospectively analyzed 311 pediatric patients with a suspected IEM using four targeted gene panels. The rate of positive diagnosis was 61.86% for intermediary metabolism defects, 32.84% for complex molecular defects, 19% for hypoglycemic/hyperglycemic events, and 17% for mitochondrial diseases, and a conclusive molecular diagnosis was established in 2-4 weeks. Forty-one patients for whom negative results were obtained with the mitochondrial diseases panel underwent subsequent analyses using the NeuroSeq panel, which groups all genes from the individual panels together with genes associated with neurological disorders (1870 genes in total). This achieved a diagnostic rate of 32%. We next evaluated the utility of a tool, Phenomizer, for differential diagnosis, and established a correlation between phenotype and molecular findings in 39.3% of patients. Finally, we evaluated the mutational architecture of the genes analyzed by determining z-scores, loss-of-function observed/expected upper bound fraction (LOEUF), and haploinsufficiency (HI) scores. In summary, targeted gene panels for specific groups of IEMs enabled rapid and effective diagnosis, which is critical for the therapeutic management of IEM patients.info:eu-repo/semantics/publishedVersio
Arginine deprivation alters microglia polarity and synergises with radiation to eradicate non arginine auxotrophic glioblastoma tumors
New approaches for the management of glioblastoma (GBM) are an urgent and unmet clinical need. Here, we illustrate that the efficacy of radiotherapy for GBM is strikingly potentiated by concomitant therapy with the arginine depleting agent ADI-PEG20 in a non-arginine auxotrophic cellular background (Arginine Succinate Synthetase 1 positive). Moreover, this combination led to durable and complete radiological and pathological response with extended disease-free survival in an orthotopic immune competent model of GBM with no significant toxicity. ADI-PEG20 not only enhances the cellular sensitivity of Arginine succinate synthetase 1 positive GBM to ionising radiation by elevated production of nitric oxide (NO) and hence generation of cytotoxic peroxynitrites, but also promotes glioma-associated macrophages/microglia infiltration into tumors and turns their classical anti-inflammatory (pro-tumor) phenotype into a pro-inflammatory (anti-tumor) phenotype. Our results provide an effective, well-tolerated and simple strategy to improve GBM treatment which merits consideration for early evaluation in clinical trials
Satisfação materna com o cuidado da enfermeira materno-infantil em Campeche, MÊxico
OBJECTIVE: Evaluate and compare maternal-satisfaction (global and areas) with maternal-child nursing care (MSMINC) and to explore the relationship of MSMINC with wait time, length of visit, and maternal age and education. METHODS: Cross-sectional descriptive study comprising 213 mothers. Group 1 (n = 84), mothers of children agedEl objetivo de este estudio fue evaluar y comparar la satisfacciĂłn materna (global/ĂĄreas) con el cuidado de la enfermera materno infantil (MSMINC) y explorar la relaciĂłn de MSMINC con el tiempo de espera, duraciĂłn de la visita, edad y educaciĂłn materna. Se trata de un estudio descriptivo transversal. Participaron 213 madres. Grupo 1, n = 84 madres de niĂąosOBJETIVO: Avaliar e comparar a satisfação materna (global e ĂĄreas) com o cuidado da enfermeira materno-infantil (SMAEMI) e explorar a relação da SMAEMI com o tempo de espera e duração da visita, idade e educação da mĂŁe. MĂTODOS: ESTUdo descritivo-transversal com a participação de 213 mĂŁes. Grupo 1, n = 84 mĂŁes de criança
Dynamical Patterns of Cattle Trade Movements
Despite their importance for the spread of zoonotic diseases, our
understanding of the dynamical aspects characterizing the movements of farmed
animal populations remains limited as these systems are traditionally studied
as static objects and through simplified approximations. By leveraging on the
network science approach, here we are able for the first time to fully analyze
the longitudinal dataset of Italian cattle movements that reports the mobility
of individual animals among farms on a daily basis. The complexity and
inter-relations between topology, function and dynamical nature of the system
are characterized at different spatial and time resolutions, in order to
uncover patterns and vulnerabilities fundamental for the definition of targeted
prevention and control measures for zoonotic diseases. Results show how the
stationarity of statistical distributions coexists with a strong and
non-trivial evolutionary dynamics at the node and link levels, on all
timescales. Traditional static views of the displacement network hide important
patterns of structural changes affecting nodes' centrality and farms' spreading
potential, thus limiting the efficiency of interventions based on partial
longitudinal information. By fully taking into account the longitudinal
dimension, we propose a novel definition of dynamical motifs that is able to
uncover the presence of a temporal arrow describing the evolution of the system
and the causality patterns of its displacements, shedding light on mechanisms
that may play a crucial role in the definition of preventive actions
Dynamical Patterns of Cattle Trade Movements
Despite their importance for the spread of zoonotic diseases, our
understanding of the dynamical aspects characterizing the movements of farmed
animal populations remains limited as these systems are traditionally studied
as static objects and through simplified approximations. By leveraging on the
network science approach, here we are able for the first time to fully analyze
the longitudinal dataset of Italian cattle movements that reports the mobility
of individual animals among farms on a daily basis. The complexity and
inter-relations between topology, function and dynamical nature of the system
are characterized at different spatial and time resolutions, in order to
uncover patterns and vulnerabilities fundamental for the definition of targeted
prevention and control measures for zoonotic diseases. Results show how the
stationarity of statistical distributions coexists with a strong and
non-trivial evolutionary dynamics at the node and link levels, on all
timescales. Traditional static views of the displacement network hide important
patterns of structural changes affecting nodes' centrality and farms' spreading
potential, thus limiting the efficiency of interventions based on partial
longitudinal information. By fully taking into account the longitudinal
dimension, we propose a novel definition of dynamical motifs that is able to
uncover the presence of a temporal arrow describing the evolution of the system
and the causality patterns of its displacements, shedding light on mechanisms
that may play a crucial role in the definition of preventive actions
[Determinants of the use of different healthcare levels in the General System of Social Security in Health in Colombia and the Unified Health System in Brazil].
OBJECTIVE:
To compare the use of different healthcare levels, and its determinants, in two different health systems, the General System of Social Security in Health (GSSSH) and the Unified Health System (UHS) in municipalities in Colombia and Brazil.
METHODS:
A cross-sectional study was carried out, based on a population survey in two municipalities in Colombia (n=2163) and two in Brazil (n=2155). Outcome variables consisted of the use of primary care services, outpatient secondary care services, and emergency care in the previous 3 months. Explanatory variables were need and predisposing and enabling factors. Bivariate and multivariate logistic regression analyses were performed by healthcare level and country.
RESULTS:
The determinants of use differed by healthcare level and country: having a chronic disease was associated with a greater use of primary and outpatient secondary care in Colombia, and was also associated with the use of emergency care in Brazil. In Colombia, persons enrolled in the contributory scheme more frequently used the services of the GSSSH than persons enrolled with subsidized contributions in primary and outpatient secondary care and more than persons without insurance in any healthcare level. In Brazil, the low-income population and those without private insurance more frequently used the UHS at any level. In both countries, the use of primary care was increased when persons knew the healthcare center to which they were assigned and if they had a regular source of care. Knowledge of the referral hospital increased the use of outpatient secondary care and emergency care.
CONCLUSIONS:
In both countries, the influence of the determinants of use differed according to the level of care used, emphasizing the need to analyze healthcare use by disaggregating it by level of care
Effect of phosphorus on the attenuation of lead and chromium
This study analyses the adsorption of Pb(II) and Cr(III) in soils. These metals are commonly found together in nature in urban wastes or industrial spillages, and the theoretical approach of the work was to evaluate the response of the soil to continuous Cr and Pb spillages to soil in terms of several physicochemical parameters. The influence of an anthropogenic input of phosphorus was evaluated. Continuous flow experiments were run in duplicates in acrylic columns (25 cm Ă 3.2 cm). The influent Cr(III) and Pb(II) solutions of 10 mg lâ1 and 25 mg lâ1 at pH 5 were pumped upward through the bottom of the columns to ensure saturation flow conditions. Also, successive experiments were run with the above concentrations of Cr(III) and Pb(II) and NaH2PO4, keeping metal to phosphorus ratio of 1:0, 1:0.1 and 1:1. Modelling parameters included Freundlich and Langmuir equations, together with the Two-site adsorption model using CXTFIT code. Results obtained allowed concluding that Pb(II) adsorption presents a certain degree of irreversibility and the continued spillages over soil increment the fraction which is not easily desorbed. Cr(III) desorption was almost complete, evidencing its high mobility in nature. The presence of an anthropogenic input of phosphorus leads to a marked increase of both Pb(II) and Cr(III) adsorption in soils. Z-potential measurements allow to discard the electrostatic attraction of Cr(III) and Pb(II) with the surface charged soil as the dominant process of metal sorption. Instead, CheaqsPro simulation allows to identify PbH2PO4 +, PbHPO4 (aq) and CrHPO4 + as the dominant species which regulate Cr(III) and Pb(II) transport in soils.Fundação para a CiĂŞncia e a Tecnologi
Characterizing and modeling citation dynamics
Citation distributions are crucial for the analysis and modeling of the
activity of scientists. We investigated bibliometric data of papers published
in journals of the American Physical Society, searching for the type of
function which best describes the observed citation distributions. We used the
goodness of fit with Kolmogorov-Smirnov statistics for three classes of
functions: log-normal, simple power law and shifted power law. The shifted
power law turns out to be the most reliable hypothesis for all citation
networks we derived, which correspond to different time spans. We find that
citation dynamics is characterized by bursts, usually occurring within a few
years since publication of a paper, and the burst size spans several orders of
magnitude. We also investigated the microscopic mechanisms for the evolution of
citation networks, by proposing a linear preferential attachment with time
dependent initial attractiveness. The model successfully reproduces the
empirical citation distributions and accounts for the presence of citation
bursts as well.Comment: 8 pages, 5 figure
Can interventions that aim to decrease Lyme disease hazard at non-domestic sites be effective without negatively affecting ecosystem health? A systematic review protocol
Background
Lyme disease (LD) is the most commonly reported, broadly distributed vector-borne disease of the northern temperate zone. It is transmitted by ticks and, if untreated, can cause skin, cardiac, nervous system and musculoskeletal disease. The distribution and incidence of LD is increasing across much of North America and Western Europe. Interventions to decrease exposure to LD hazard by encouraging behavioural change have low acceptance in high risk groups, and a safe, effective human LD vaccine is not presently available. As a result, habitat level interventions to decrease LD hazard itself (i.e. levels of infected ticks) have been proposed. However, some interventions may potentially negatively affect ecosystem health, and consequentially be neither desirable, nor politically feasible. This systematic review will catalogue interventions that aim to reduce LD hazard at non-domestic sites, and examine the evidence supporting those which are unlikely to negatively affect ecosystem health.
Methods
The review will be carried out in two steps. First, a screening and cataloguing stage will be conducted to identify and characterise interventions to decrease LD hazard at non-domestic sites. Secondly, the subset of interventions identified during cataloguing as unlikely to negatively affect ecosystem health will be investigated. In the screening and cataloguing step literature will be collected through database searching using pre-chosen search strings, hand-searching key journals and reviewing the websites of public health bodies. Further references will be identified by contacting stakeholders and researchers. Article screening and assessment of the likely effects of interventions on ecosystem health will be carried out independently by two reviewers. A third reviewer will be consulted if disagreements arise. The cataloguing step results will be presented in tables. Study quality will then be assessed independently by two reviewers, using adapted versions of established tools developed in healthcare research. These results will be presented in a narrative synthesis alongside tables. Though a full meta-analysis is not expected to be possible, if sub-groups of studies are sufficiently similar to compare, a partial meta-analysis will be carried out
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