Comparison of Cytokine Responses in Ecuadorian Children Infected with Giardia, Ascaris, or Both Parasites.

More than 2 billion people are infected with parasites globally, and the majority have coinfections. Intestinal protozoa and helminths induce polarizing CD4(+) T-helper cell 1 (Th1) mediated cytokine responses within the host. Such immune polarization may inhibit the ability of the host to mount an adequate immune response for pathogen clearance to concurrent pathogens. The current study evaluated the plasma cytokine profile in Ascaris and Giardia coinfected children compared with Giardia- and Ascaris-only infected children. Fecal samples and blood samples were collected from asymptomatic 3-year-old children living in the district of Quininde, Ecuador. Stool samples that tested positive for Giardia lamblia-only, Ascaris lumbricoides-only, or G. lamblia and A. lumbricoides coinfections were confirmed by quantitative real-time polymerase chain reaction. Plasma samples from the study subjects were used to quantitate cytokines. A total of 39 patients were evaluated. Children with coinfection had a significant decrease in Th1 cytokine production, interleukin 2 (IL-2) (P < 0.05), IL-12 (P < 0.05), and tumor necrosis factor alpha (P < 0.05) compared with Giardia-only infected children. Coinfected children had an increase in IL-10/interferon gamma (IFN-γ) ratio compared with uninfected (P < 0.05) and Ascaris alone (P < 0.05). The increased IL-10/IFN-γ ratio in the setting of decreased Th1 cytokine response indicates Th2 polarization in the coinfected group. Reduced Th1 cytokines in children coinfected with Ascaris and Giardia may impair the host's ability to eradicate Giardia infection leading to chronic giardiasis

Placental capillary pericytes release excess extracellular vesicles under hypoxic conditions inducing a pro-angiogenic profile in term pregnancy

Supplementary data available online at: https://www.sciencedirect.com/science/article/pii/S0006291X2300181X#appsec1Copyright © 2023 The Authors. Pericytes are multifunctional cells wrapped around capillary endothelia, essential for vascular health, development, and blood flow regulation, although their role in human placental chorionic villi has not been fully explored. The second half of normal pregnancy is characterized by a progressive decline in placental and fetal oxygen levels which, by term, comprises a substantial degree of hypoxia. We hypothesized this hypoxia would stimulate pericyte regulation of chorionic villous capillary function. This study's objective was to investigate the role of hypoxia on normal term placental pericytes (PLVP) and their signaling to endothelial cells. First, we confirmed fetoplacental hypoxia at term by a new analysis of umbilical arterial blood oxygen tension of 3,010 healthy singleton neonates sampled at caesarean section and before labor. We then measured the release of cytokines, chemokines, and small extracellular vesicles (PLVPsv), from PLVP cultured at 20%, 8% and 1% O2. As O2 levels decreased, secreted cytokines and chemokines [interleukin-6 (IL-6), interleukin-1α (IL-1α) and vascular endothelial growth factor (VEGF)], and small extracellular vesicle markers, (Alix, Syntenin and CD9) increased significantly in the culture supernatants. When primary human umbilical vein endothelial cells (HUVEC) were cultured with PLVPsv, polygon formation, number, and tube formation length was significantly increased compared to cells not treated with PLVPsv, indicating PLVPsv stimulated angiogenesis. We conclude that adding PLVPsv stimulates angiogenesis and vessel stabilization on neighboring endothelial cells in response to hypoxia in term pregnancy compared to no addition of PLVPsv. Our finding that PLVP can release angiogenic molecules via extracellular vesicles in response to hypoxia may apply to other organ systems.MRC Program Grant (MR/J003360/1); rad Sutherland is supported by the National Health and Medical Research Council of Australia (APP1137776)

Spectral-based mesh segmentation

In design and manufacturing, mesh segmentation is required for FACE construction in boundary representation (BRep), which in turn is central for featurebased design, machining, parametric CAD and reverse engineering, among others -- Although mesh segmentation is dictated by geometry and topology, this article focuses on the topological aspect (graph spectrum), as we consider that this tool has not been fully exploited -- We preprocess the mesh to obtain a edgelength homogeneous triangle set and its Graph Laplacian is calculated -- We then produce a monotonically increasing permutation of the Fiedler vector (2nd eigenvector of Graph Laplacian) for encoding the connectivity among part feature submeshes -- Within the mutated vector, discontinuities larger than a threshold (interactively set by a human) determine the partition of the original mesh -- We present tests of our method on large complex meshes, which show results which mostly adjust to BRep FACE partition -- The achieved segmentations properly locate most manufacturing features, although it requires human interaction to avoid over segmentation -- Future work includes an iterative application of this algorithm to progressively sever features of the mesh left from previous submesh removal

Large-Scale Streamwise Vortices in Turbulent Channel Flow Induced by Active Wall Actuations

© 2017, Springer Science+Business Media B.V., part of Springer Nature. Direct numerical simulations of turbulent flow in a plane channel using spanwise alternatively distributed strips (SADS) are performed to investigate the characteristics of large-scale streamwise vortices (LSSVs) induced by small-scale active wall actuations, and their role in suppressing flow separation. SADS control is obtained by alternatively applying out-of-phase control (OPC) and in-phase control (IPC) to the wall-normal velocity component of the lower channel wall, in the spanwise direction. Besides the non-controlled channel flow simulated as a reference, four controlled cases with 1, 2, 3 and 4 pairs of OPC/IPC strips are studied at M = 0.2 and Re = 6,000, based on the bulk velocity and the channel half height. The case with 2 pairs of strips, whose width is Δz+ = 264 based on the friction velocity of the non-controlled case, is the most effective in terms of generating large-scale motions. It is also found that the OPC (resp. IPC) strips suppress (resp. enhance) the coherent structures and that leads to the creation of a vertical shear layer, which is responsible for the LSSVs presence. They are in a statistically steady state and their cores are located between two neighbouring OPC and IPC strips. These motions contribute significantly to the momentum transport in the wall-normal and spanwise directions showing potential for flow separation suppression

The metrics and correlates of physician migration from Africa

<p>Abstract</p> <p>Background</p> <p>Physician migration from poor to rich countries is considered an important contributor to the growing health workforce crisis in the developing world. This is particularly true for Africa. The perceived magnitude of such migration for each source country might, however, depend on the choice of metrics used in the analysis. This study examined the influence of choice of migration metrics on the rankings of African countries that suffered the most physician migration, and investigated the correlates of physician migration.</p> <p>Methods</p> <p>Ranking and correlational analyses were conducted on African physician migration data adjusted for bilateral net flows, and supplemented with developmental, economic and health system data. The setting was the 53 African birth countries of African-born physicians working in nine wealthier destination countries. Three metrics of physician migration were used: total number of physician émigrés; emigration fraction defined as the proportion of the potential physician pool working in destination countries; and physician migration density defined as the number of physician émigrés per 1000 population of the African source country.</p> <p>Results</p> <p>Rankings based on any of the migration metrics differed substantially from those based on the other two metrics. Although the emigration fraction and physician migration density metrics gave proportionality to the migration crisis, only the latter was consistently associated with source countries' workforce capacity, health, health spending, economic and development characteristics. As such, higher physician migration density was seen among African countries with relatively higher health workforce capacity (0.401 ≤ <it>r </it>≤ 0.694, <it>p </it>≤ 0.011), health status, health spending, and development.</p> <p>Conclusion</p> <p>The perceived magnitude of physician migration is sensitive to the choice of metrics. Complementing the emigration fraction, the physician migration density is a metric which gives a different but proportionate picture of which African countries stand to lose relatively more of its physicians with unchecked migration. The nature of health policies geared at health-worker migration can be expected to depend on the choice of migration metrics.</p

Analytical model for the calculation of lateral velocity distributions in potential cross-sections

[EN] The hydraulic modeling of water depth and flow velocities in open channel flows that were fitted by power-law cross-section stand out for their versatility, allowing their use in numerous practical applications, both in natural and artificial channels. The determination of the hydraulic variables of depth and average velocity has been widely studied in potential cross-sections; however, the variation seen in these variables along the cross-section was not found in the literature. Knowledge of this variation allows the development of studies (e.g. to know the approximate damage in different areas of the cross-section, to analyse sediment transport, or other applications in river hydraulics). This paper presents a methodology which allows calculation of the hydraulic variables in any area of a power-law cross-section. The methodology is applied to symmetrical cross-sections, comparing its generated results with the obtained values by different computational hydraulic codes, which are thoroughly accepted by scientific community, such as CES, HEC-RAS and IBER. The obtained predictions of hydraulic parameters (using the explicit formulation described in this research) present very low errors when compared with results of other models, with great computational cost. These errors reach a root mean square error (RMSE) of 0.13 and 0.05 in the determination of velocities' lateral distribution and the ratio between velocity and average velocity. These values indicate a very successful validation for the analysed symmetrical sections.[ES] La modelización hidráulica de calados y velocidades de flujo, en cauces con secciones que admiten una representación de tipo potencial, se destaca por su versatilidad, permitiendo su utilización en numerosas aplicaciones prácticas tanto en canales naturales como artificiales. El cálculo de las variables hidráulicas (calado y velocidad media) ha sido ampliamente estudiado para este tipo de secciones. Sin embargo, en la literatura técnica no se han encontrado estudios que muestren la variación de estas magnitudes a lo largo de la sección transversal. El conocimiento de esta variación permite desarrollar estudios (ejemplo: conocer de manera aproximada los daños en diferentes zonas de la sección, analizar el transporte de sedimentos, estudiar los procesos de erosión u otras aplicaciones en hidráulica fluvial). Presentamos una metodología que permite el cálculo de las variables hidráulicas en cualquier zona de una sección tipo potencial. La metodología es aplicada a secciones simétricas, comparando los resultados generados con los obtenidos por diferentes códigos hidráulicos computacionales ampliamente aceptados por la comunidad científica (p-e- CES, HECRAS e IBER). Las predicciones de los parámetros hidráulicos obtenidas (usando la formulación explícita descrita en este artículo) presentan errores muy bajos, en comparación con otros modelos con mayor costo computacional. Estos errores alcanzan un valor promedio para la raíz del error cuadrático medio (RMSE) en el cálculo de la distribución lateral de velocidades de 0.13 y de 0.05, en el cálculo de la relación de velocidades respecto a la velocidad media. Estos valores indican una validación muy satisfactoria para las secciones simétricas analizadas.Sánchez-Romero, F.; Pérez-Sánchez, M.; López Jiménez, PA. (2018). Modelo analítico para el cálculo de distribuciones de velocidad laterales en secciones tipo potencial-ley. RIBAGUA - Revista Iberoamericana del Agua. 5(1):29-47. doi:10.1080/23863781.2018.1442189S29475

Minocycline Synergizes with N-Acetylcysteine and Improves Cognition and Memory Following Traumatic Brain Injury in Rats

Background: There are no drugs presently available to treat traumatic brain injury (TBI). A variety of single drugs have failed clinical trials suggesting a role for drug combinations. Drug combinations acting synergistically often provide the greatest combination of potency and safety. The drugs examined (minocycline (MINO), N-acetylcysteine (NAC), simvastatin, cyclosporine A, and progesterone) had FDA-approval for uses other than TBI and limited brain injury in experimental TBI models. Methodology/Principal Findings: Drugs were dosed one hour after injury using the controlled cortical impact (CCI) TBI model in adult rats. One week later, drugs were tested for efficacy and drug combinations tested for synergy on a hierarchy of behavioral tests that included active place avoidance testing. As monotherapy, only MINO improved acquisition of the massed version of active place avoidance that required memory lasting less than two hours. MINO-treated animals, however, were impaired during the spaced version of the same avoidance task that required 24-hour memory retention. Coadministration of NAC with MINO synergistically improved spaced learning. Examination of brain histology 2 weeks after injury suggested that MINO plus NAC preserved white, but not grey matter, since lesion volume was unaffected, yet myelin loss was attenuated. When dosed 3 hours before injury, MINO plus NAC as single drugs had no effect on interleukin-1 formation; together they synergistically lowered interleukin-1 levels. This effect on interleukin-1 was not observed when th

Search for CP violation in D+→ϕπ+ and D+s→K0Sπ+ decays

A search for CP violation in D + → ϕπ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fb−1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (−0.04 ± 0.14 ± 0.14)% for candidates with K − K + mass within 20 MeV/c 2 of the ϕ meson mass. A search for a CP -violating asymmetry that varies across the ϕ mass region of the D + → K − K + π + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+s→K0Sπ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%

Equity In Health care financing in low-and middle-income countries: A systematic review of evidence from studies using benefit and financing incidence analyses

© 2016 Asante et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction: Health financing reforms in low-and middle-income countries (LMICs) over the past decades have focused on achieving equity in financing of health care delivery through universal health coverage. Benefit and financing incidence analyses are two analytical methods for comprehensively evaluating how well health systems perform on these objectives. This systematic review assesses progress towards equity in health care financing in LMICs through the use of BIA and FIA. Methods and Findings: Key electronic databases including Medline, Embase, Scopus, Global Health, CinAHL, EconLit and Business Source Premier were searched. We also searched the grey literature, specifically websites of leading organizations supporting health care in LMICs. Only studies using benefit incidence analysis (BIA) and/or financing incidence analysis (FIA) as explicit methodology were included. A total of 512 records were obtained from the various sources. The full texts of 87 references were assessed against the selection criteria and 24 were judged appropriate for inclusion. Twelve of the 24 studies originated from sub-Saharan Africa, nine from the Asia-Pacific region, two from Latin America and one from the Middle East. The evidence points to a pro-rich distribution of total health care benefits and progressive financing in both sub-Saharan Africa and Asia-Pacific. In the majority of cases, the distribution of benefits at the primary health care level favoured the poor while hospital level services benefit the better-off. A few Asian countries, namely Thailand, Malaysia and Sri Lanka, maintained a pro-poor distribution of health care benefits and progressive financing. Conclusion: Studies evaluated in this systematic review indicate that health care financing in LMICs benefits the rich more than the poor but the burden of financing also falls more on the rich. There is some evidence that primary health care is pro-poor suggesting a greater investment in such services and removal of barriers to care can enhance equity. The results overall suggest that there are impediments to making health care more accessible to the poor and this must be addressed if universal health coverage is to be a reality

Dissecting Oct3/4-Regulated Gene Networks in Embryonic Stem Cells by Expression Profiling

POU transcription factor Pou5f1 (Oct3/4) is required to maintain ES cells in an undifferentiated state. Here we show that global expression profiling of Oct3/4-manipulated ES cells delineates the downstream target genes of Oct3/4. Combined with data from genome-wide chromatin-immunoprecipitation (ChIP) assays, this analysis identifies not only primary downstream targets of Oct3/4, but also secondary or tertiary targets. Furthermore, the analysis also reveals that downstream target genes are regulated either positively or negatively by Oct3/4. Identification of a group of genes that show both activation and repression depending on Oct3/4 expression levels provides a possible mechanism for the requirement of appropriate Oct3/4 expression to maintain undifferentiated ES cells. As a proof-of-principle study, one of the downstream genes, Tcl1, has been analyzed in detail. We show that Oct3/4 binds to the promoter region of Tcl1 and activates its transcription. We also show that Tcl1 is involved in the regulation of proliferation, but not differentiation, in ES cells. These findings suggest that the global expression profiling of gene-manipulated ES cells can help to delineate the structure and dynamics of gene regulatory networks