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RNA interference (RNAi) mediated by the small interfering RNA (siRNA) pathway is a major antiviral mechanism in insects. This pathway is triggered when double-stranded RNA (dsRNA) produced during virus replication is recognized by Dicer-2, leading to the formation of virus-derived siRNA duplexes. These siRNAs are loaded onto the programmable nuclease Argonaute-2 (AGO2), with one strand serving as a guide to target and cleave fully complementary sequences of viral RNAs. While siRNAs are generated from viral dsRNA, the specific viral RNA species targeted for silencing during RNA virus replication remains unclear. In this study, we characterized the primary viral RNA targets of the Drosophila siRNA pathway during infections caused by negative and positive RNA viruses, namely Vesicular stomatitis virus (VSV) and Sindbis virus (SINV). Our findings reveal that polyadenylated transcripts of VSV and SINV are the major targets of silencing by the siRNA pathway during infection, likely when they are poised for translation. Consistent with earlier findings, we show that AGO2 is associated with ribosomes in control and virus infected cells. Therefore, we propose that the inhibition of the replication of RNA viruses in Drosophila results from the silencing of incoming viral transcripts, facilitated by the association of AGO2 with ribosomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Silva 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.)

Knowledge about seafloor depth, or bathymetry, is crucial for various marine activities, including scientific research, offshore industry, safety of navigation, and ocean exploration. Mapping the central Arctic Ocean is challenging due to the presence of perennial sea ice, which limits data collection to icebreakers, submarines, and drifting ice stations. The International Bathymetric Chart of the Arctic Ocean (IBCAO) was initiated in 1997 with the goal of updating the Arctic Ocean bathymetric portrayal. The project team has since released four versions, each improving resolution and accuracy. Here, we present IBCAO Version 5.0, which offers a resolution four times as high as Version 4.0, with 100 × 100 m grid cells compared to 200 × 200 m. Over 25% of the Arctic Ocean is now mapped with individual depth soundings, based on a criterion that considers water depth. Version 5.0 also represents significant advancements in data compilation and computing techniques. Despite these improvements, challenges such as sea-ice cover and political dynamics still hinder comprehensive mapping., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The MICA gene encodes a glycoprotein upregulated upon cellular stress, particularly in oxidative stress, intracellular infections, and tumorigenesis. This stress-signaling molecule interacts with the activating receptor NKG2D from Natural Killer (NK) and some T lymphocytes, stimulating their cytotoxic activity. MICA is encoded within the human Major Histocompatibility Complex next to the HLA-B locus and is highly polymorphic. MICA might be absent from chromosome 6 due to a large deletion of approximately 100 Kb between HLA-B and MICB. Therefore, some individuals may not produce any isoform of MICA. The distribution of this phenotype may vary among different populations. We evaluated the distribution of the MICA*del and other MICA null alleles in different biogeographic regions and the Linkage Disequilibrium (LD) pattern between this allele and HLA-B. We detected at least two different patterns of deletion, one with full deletion of MICA and surrounding sequences and one partial MICA deletion. The presence of different patterns of deletion suggests independent deletion events. We confirm that the previously described MICA*del allele is mainly associated with B*48 and MICB*009N in Asia and America, but other haplotypes also occur. While most samples with complete or partial MICA deletion are heterozygous and present one functional copy of both MICA and MICB genes, we detected two samples with no functional MICA and one with no functional MIC genes. Therefore, other mechanisms might be in place to compensate for the absence of MIC molecules., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Background: Increased awareness of the factors contributing to the diagnostic disparities seen in bipolar disorder between individuals of different heritage is needed to achieve equity in diagnosis and treatment. One such inequity is the provision of earlier treatment. Earlier treatment of patients diagnosed with bipolar disorder may prolong time to recurrence of mood episodes and reduce functional impairment and other poor outcomes associated with disease progression. The aim of this post hoc analysis was to study the efficacy and safety of long-acting injectable aripiprazole once-monthly 400 mg (AOM 400) in patients with earlier-stage bipolar I disorder (BP-I). Data from a 52-week multicenter, double-blind, placebo-controlled, randomized withdrawal trial of AOM 400 versus placebo in patients with BP‑I (NCT01567527) were analyzed. Those patients in the lowest quartiles for age (18-≤32 years; n = 70) or disease duration (0.13-≤4.6 years; n = 67) at baseline were categorized with earlier-stage BP-I. The primary endpoint was time from randomization to recurrence of any mood episode. Other endpoints included proportion of patients with recurrence of any mood episode, and change from baseline in Young Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) total scores., Results: Maintenance treatment with AOM 400 significantly delayed time to recurrence of any mood episode versus placebo in patients aged 18-≤32 years (hazard ratio [HR]: 2.46 [95% confidence interval (CI) 1.09, 5.55]; p = 0.0251) or with disease duration 0.13-≤4.6 years (HR: 3.21 [95% CI 1.35, 7.65]; p = 0.005). This was largely driven by a lower proportion of patients in the AOM 400 group with YMRS total score ≥15 or clinical worsening. Changes from baseline in MADRS total score in both earlier-stage groups indicated AOM 400 did not worsen depression versus placebo. The safety profile of AOM 400 was consistent with the original study. Note that the original study included patients who had previously been stabilized on AOM 400 monotherapy, which may have enriched the population with patients who respond to and tolerate AOM 400., Conclusions: In this post hoc analysis, AOM 400 prolonged time to recurrence of any mood episode versus placebo in earlier-stage BP-I. These findings support early initiation of maintenance treatment with AOM 400., (© 2024. The Author(s).)

Objective: The present study aimed to evaluate the association between muscle mass variation, estimated by different equations, during hospitalization with the energy and protein intake and clinical and nutrition outcomes of patients using nutrition support., Methods: A prospective observational study with patients older than 18 years in use of enteral and/or parenteral nutrition therapy and monitored by the Nutritional Therapy Committee between December 14, 2021, and December 14, 2022. Data were collected from the electronic records and were applied in 11 equations to estimate the four different portions of muscle mass of patients receiving nutrition support at the beginning and the end of hospitalization., Results: A total of 261 patients were evaluated, with a median age of 61.0 (49.0-69.75) years, and 106 were women (40.6%). According to the nutrition diagnosis, several participants had severe malnutrition (39.5%). The most muscle mass estimation equations indicated a reduction of muscle mass during hospitalization. All patients presented negative energy and protein balances during hospitalization, but greater protein intake increased the lean soft tissue. Also, the greater the number of infections, metabolic complications, and scheduled diet interruption, the greater was the chance of losing muscle mass., Conclusion: There can be an association between the variation in muscle mass and energy and protein intake during hospitalization of patients using nutrition support. In addition, variation in muscle mass was associated with complications from nutrition support. The results emphasize the importance of anthropometric measurements to estimate muscle mass when other methods are not available., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Background: Mosquito borne viruses, such as dengue, Zika, yellow fever and Chikungunya, cause millions of infections every year. These viruses are mostly transmitted by two urban-adapted mosquito species, Aedes aegypti and Aedes albopictus. Although mechanistic understanding remains largely unknown, Aedes mosquitoes may have unique adaptations that lower the impact of viral infection. Recently, we reported the identification of an Aedes specific double-stranded RNA binding protein (dsRBP), named Loqs2, that is involved in the control of infection by dengue and Zika viruses in mosquitoes. Preliminary analyses suggested that the loqs2 gene is a paralog of loquacious (loqs) and r2d2, two co-factors of the RNA interference (RNAi) pathway, a major antiviral mechanism in insects., Results: Here we analyzed the origin and evolution of loqs2. Our data suggest that loqs2 originated from two independent duplications of the first double-stranded RNA binding domain of loqs that occurred before the origin of the Aedes Stegomyia subgenus, around 31 million years ago. We show that the loqs2 gene is evolving under relaxed purifying selection at a faster pace than loqs, with evidence of neofunctionalization driven by positive selection. Accordingly, we observed that Loqs2 is localized mainly in the nucleus, different from R2D2 and both isoforms of Loqs that are cytoplasmic. In contrast to r2d2 and loqs, loqs2 expression is stage- and tissue-specific, restricted mostly to reproductive tissues in adult Ae. aegypti and Ae. albopictus. Transgenic mosquitoes engineered to express loqs2 ubiquitously undergo developmental arrest at larval stages that correlates with massive dysregulation of gene expression without major effects on microRNAs or other endogenous small RNAs, classically associated with RNA interference., Conclusions: Our results uncover the peculiar origin and neofunctionalization of loqs2 driven by positive selection. This study shows an example of unique adaptations in Aedes mosquitoes that could ultimately help explain their effectiveness as virus vectors., (© 2024. The Author(s).)

Context: Reduced muscle mass is linked to poor outcomes in both inpatients and outpatients, highlighting the importance of muscle mass assessment in clinical practice. However, laboratory methods to assess muscle mass are not yet feasible for routine use in clinical practice because of limited availability and high costs., Objective: This work aims to review the literature on muscle mass prediction by anthropometric equations in adults or older people., Data Sources: The following databases were searched for observational studies published until June 2022: MEDLINE, Embase, Scopus, SPORTDiscus, and Web of Science., Data Extraction: Of 6437 articles initially identified, 63 met the inclusion criteria for this review. Four independent reviewers, working in pairs, selected and extracted data from those articles., Data Analysis: Two studies reported new equations for prediction of skeletal muscle mass: 10 equations for free-fat mass and lean soft tissue, 22 for appendicular lean mass, 7 for upper-body muscle mass, and 7 for lower-body muscle mass. Twenty-one studies validated previously proposed equations. This systematic review shows there are numerous equations in the literature for muscle mass prediction, and most are validated for healthy adults. However, many equations were not always accurate and validated in all groups, especially people with obesity, undernourished people, and older people. Moreover, in some studies, it was unclear if fat-free mass or lean soft tissue had been assessed because of an imprecise description of muscle mass terminology., Conclusion: This systematic review identified several feasible, practical, and low-cost equations for muscle mass prediction, some of which have excellent accuracy in healthy adults, older people, women, and athletes. Malnourished individuals and people with obesity were understudied in the literature, as were older people, for whom there are only equations for appendicular lean mass., Systematic Review Registration: PROSPERO registration number CRD42021257200., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sphingolipids (SLs) are essential components of all eukaryotic cellular membranes. In fungi, plants and many protozoa, the primary SL is inositol-phosphorylceramide (IPC). Trypanosoma cruzi is a protozoan parasite that causes Chagas disease (CD), a chronic illness for which no vaccines or effective treatments are available. IPC synthase (IPCS) has been considered an ideal target enzyme for drug development because phosphoinositol-containing SL is absent in mammalian cells and the enzyme activity has been described in all parasite forms of T. cruzi. Furthermore, IPCS is an integral membrane protein conserved amongst other kinetoplastids, including Leishmania major, for which specific inhibitors have been identified. Using a CRISPR-Cas9 protocol, we generated T. cruzi knockout (KO) mutants in which both alleles of the IPCS gene were disrupted. We demonstrated that the lack of IPCS activity does not affect epimastigote proliferation or its susceptibility to compounds that have been identified as inhibitors of the L. major IPCS. However, disruption of the T. cruzi IPCS gene negatively affected epimastigote differentiation into metacyclic trypomastigotes as well as proliferation of intracellular amastigotes and differentiation of amastigotes into tissue culture-derived trypomastigotes. In accordance with previous studies suggesting that IPC is a membrane component essential for parasite survival in the mammalian host, we showed that T. cruzi IPCS null mutants are unable to establish an infection in vivo, even in immune deficient mice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Dos Santos 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.)

Background: Electronic cigarette (e-cigarette) vapour is gaining popularity as an alternative to tobacco smoking and can induce acute lung injury. However, the specific role of nicotine in e-cigarette vapour and its long-term effects on the airways, lung parenchyma and vasculature remain unclear., Results: In vitro exposure to nicotine-containing e-cigarette vapour extract (ECVE) or to nicotine-free e-cigarette vapour extract (NF ECVE) induced changes in gene expression of epithelial cells and pulmonary arterial smooth muscle cells (PASMCs), but ECVE in particular caused functional alterations ( e.g. a decrease in human and mouse PASMC proliferation by 29.3±5.3% and 44.3±8.4%, respectively). Additionally, acute inhalation of nicotine-containing e-cigarette vapour (ECV) but not nicotine-free e-cigarette vapour (NF ECV) increased pulmonary endothelial permeability in isolated lungs. Long-term in vivo exposure of mice to ECV for 8 months significantly increased the number of inflammatory cells, in particular lymphocytes, compared to control and NF ECV in the bronchoalveolar fluid (BALF) (ECV: 853.4±150.8 cells·mL -1 ; control: 37.0±21.1 cells·mL -1 ; NF ECV: 198.6±94.9 cells·mL -1 ) and in lung tissue (ECV: 25.7±3.3 cells·mm -3 ; control: 4.8±1.1 cells·mm -3 ; NF ECV: 14.1±2.2 cells·mm -3 ). BALF cytokines were predominantly increased by ECV. Moreover, ECV caused significant changes in lung structure and function ( e.g. increase in airspace by 17.5±1.4% compared to control), similar to mild tobacco smoke-induced alterations, which also could be detected in the NF ECV group, albeit to a lesser degree. In contrast, the pulmonary vasculature was not significantly affected by ECV or NF ECV., Conclusions: NF ECV components induce cell type-specific effects and mild pulmonary alterations, while inclusion of nicotine induces significant endothelial damage, inflammation and parenchymal alterations., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2023.)

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are distinct clinicopathological subtypes of frontotemporal lobar degeneration. They both have atypical parkinsonism, and they usually have distinct clinical features. The most common clinical presentation of PSP is Richardson syndrome, and the most common presentation of CBD is corticobasal syndrome. In this report, we describe a patient with a five-year history of Richardson syndrome and a family history of PSP in her mother and sister. A tau PET scan ( 18 F-APN-1607) revealed low-to-moderate uptake in the substantia nigra, globus pallidus, thalamus and posterior cortical areas, including temporal, parietal and occipital cortices. Neuropathological evaluation revealed widespread neuronal and glial tau pathology in cortical and subcortical structures, including tufted astrocytes in the motor cortex, striatum and midbrain tegmentum. The subthalamic nucleus had mild-to-moderate neuronal loss with globose neurofibrillary tangles, consistent with PSP. On the other hand, there were also astrocytic plaques, a pathological hallmark of CBD, in the neocortex and striatum. To further characterize the mixed pathology, we applied two machine learning-based diagnostic pipelines. These models suggested diagnoses of PSP and CBD depending on the brain region - PSP in the motor cortex and superior frontal gyrus and CBD in caudate nucleus. Western blots of insoluble tau from motor cortex showed a banding pattern consistent with mixed features of PSP and CBD, whereas tau from the superior frontal gyrus showed a pattern consistent with CBD. Real-time quaking-induced conversion (RT-QuIC) using brain homogenates from the motor cortex and superior frontal gyrus showed ThT maxima consistent with PSP, while reaction kinetics were consistent with CBD. There were no pathogenic variants in MAPT with whole genome sequencing. We conclude that this patient had an unclassified tauopathy and features of both PSP and CBD. The different pathologies in specific brain regions suggests caution in diagnosis of tauopathies with limited sampling., (© 2023. The Author(s).)

Background: During the COVID-19 pandemic in 2020, concerns were raised about the potential impact of pandemic-related social distancing measures on existing health disparities among sexual and gender minority (SGM) young adults, including HIV transmission risk and intimate partner violence (IPV). Another concern was the potential for increased methamphetamine use during the pandemic, which is a known risk factor for HIV transmission and IPV., Methods: The present analysis examines the impact of COVID-19 social distancing (social distancing and quarantining) and methamphetamine use on HIV risk and IPV in a combined dataset from 3 cohort studies of SGM young adults (two in Los Angeles and one in Chicago) from May 2020 to April 2021 (n = 1142). Bivariate analyses and multivariable logistic regressions were estimated., Results: The median age was 26. All participants were assigned male at birth and most participants were men (93.8%). The largest racial groups were Hispanic/Latinx (44.6%) and Black (29.0%). In adjusted models methamphetamine use was consistently associated with having a new sex partner, higher numbers of sex partners, and experience of IPV, during the pandemic. Reporting no social distancing and reporting one social distancing behavior, were associated with experience of IPV relative to reporting 2 social distancing behaviors. Social distancing was not associated with sexual risk behavior or Pre-exposure Prophylaxis use., Conclusions: SGM young adults live at the intersection of multiple vulnerabilities during the COVID-19 pandemic. Addiction services, HIV prevention services, and violence support services should be prepared to support young adult SGM needs, particularly those who use methamphetamine., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The achievement of clinically viable methodologies to simulate the hemodynamics in patient-specific coronary arteries is still a major challenge. Therefore, the novelty of this work is attained by the introduction of the viscoelastic property of blood in the numerical simulations, to study the role of the left coronary artery (LCA) geometry configuration in the atherosusceptibility. Apparently healthy patients were used and four different methodologies were tested. The methodology giving the most accurate results at the same time of having the lowest computational time is the one considering the viscoelastic property of blood and computational fluid dynamics. A Pearson correlation analysis was used to highlight relationships between geometric configuration and hemodynamic descriptors based on the simulated wall shear stress (WSS). The left main stem (LMS) has the greatest atherosusceptibility followed by the left anterior descending artery (LAD) since the relative residence time (RRT) average values are 3.81 and 3.70 Pa -1 , respectively. The geometric parameters with relevant contribution to directional flow change are the cross-sectional areas, especially the one of LMS segment (A LMS ), and the curvature of LMS segment. For LMS and LAD segments, when A LMS increases, blood flow disturbance (r = 0.81 in LMS and r = 0.74 in LAD) and atherosusceptibility (r = 0.84 in LMS and r = 0.85 in LAD) increases. When the LMS curvature decreases, the WSS magnitude (r = 0.80 in LMS and r = 0.83 in LAD) decreases, and disturbance (r=-0.80 in LMS and r=-0.91 in LAD) and atherosusceptibility (r=-0.74 in LMS and r=-0.74 in LAD) increases.

Preeclampsia (PE) is a pregnancy-specific syndrome featuring intense activation of circulating monocytes and an imbalance between pro- and anti-inflammatory cytokines. The present study evaluated the immunomodulatory effect of silibinin (Sb) on the expression of surface markers and the nuclear transcription factor NF-κB signalling pathway of monocytes from preeclamptic women. Monocytes were cultured with or without Sb, and the mean fluorescence intensity of the surface molecules TLR4, CD64, and CD163 as well as the intracellular transcription factors IκB-α and NF-κBp65 was analysed by flow cytometry. The concentration of cytokines in the monocyte culture supernatant was determined by cytometric bead array and ELISA immunoassay. The results showed that the in vitro treatment of monocytes from preeclamptic women with Sb downregulated the endogenous activation of NF-κB and the expression of surface receptors TLR4 and CD64, and reduced the synthesis of the pro-inflammatory cytokines interleukin 1 (IL-1β), IL-6, IL-8, IL-12p70, IL-23, and tumour necrosis factor alpha (TNF-α) compared with cultures not treated with Sb. The presence of this flavonoid in monocyte cultures increased the expression of CD163 and IκBα and the release of IL-10 and transforming growth factor beta (TGF-β) in the culture supernatants, polarising these cells from the M1-like profile to the M2-like profile. The anti-inflammatory activity of Sb on the NF-κB activation pathway and induction of cell polarisation to the M2 profile was confirmed by an in vitro assay using monocytes from healthy, non-pregnant women. Treatment of monocytes from preeclamptic women with Sb polarises the cells to the M2-like phenotype, suggesting that this flavonoid has an immunomodulatory effect on the sterile inflammation characteristic of PE., (Copyright © 2020 Elsevier B.V. All rights reserved.)

No treatment for frontotemporal dementia (FTD), the second most common type of early-onset dementia, is available, but therapeutics are being investigated to target the 2 main proteins associated with FTD pathological subtypes: TDP-43 (FTLD-TDP) and tau (FTLD-tau). Testing potential therapies in clinical trials is hampered by our inability to distinguish between patients with FTLD-TDP and FTLD-tau. Therefore, we evaluated truncated stathmin-2 (STMN2) as a proxy of TDP-43 pathology, given the reports that TDP-43 dysfunction causes truncated STMN2 accumulation. Truncated STMN2 accumulated in human induced pluripotent stem cell-derived neurons depleted of TDP-43, but not in those with pathogenic TARDBP mutations in the absence of TDP-43 aggregation or loss of nuclear protein. In RNA-Seq analyses of human brain samples from the NYGC ALS cohort, truncated STMN2 RNA was confined to tissues and disease subtypes marked by TDP-43 inclusions. Last, we validated that truncated STMN2 RNA was elevated in the frontal cortex of a cohort of patients with FTLD-TDP but not in controls or patients with progressive supranuclear palsy, a type of FTLD-tau. Further, in patients with FTLD-TDP, we observed significant associations of truncated STMN2 RNA with phosphorylated TDP-43 levels and an earlier age of disease onset. Overall, our data uncovered truncated STMN2 as a marker for TDP-43 dysfunction in FTD.

Bathymetry (seafloor depth), is a critical parameter providing the geospatial context for a multitude of marine scientific studies. Since 1997, the International Bathymetric Chart of the Arctic Ocean (IBCAO) has been the authoritative source of bathymetry for the Arctic Ocean. IBCAO has merged its efforts with the Nippon Foundation-GEBCO-Seabed 2030 Project, with the goal of mapping all of the oceans by 2030. Here we present the latest version (IBCAO Ver. 4.0), with more than twice the resolution (200 × 200 m versus 500 × 500 m) and with individual depth soundings constraining three times more area of the Arctic Ocean (∼19.8% versus 6.7%), than the previous IBCAO Ver. 3.0 released in 2012. Modern multibeam bathymetry comprises ∼14.3% in Ver. 4.0 compared to ∼5.4% in Ver. 3.0. Thus, the new IBCAO Ver. 4.0 has substantially more seafloor morphological information that offers new insights into a range of submarine features and processes; for example, the improved portrayal of Greenland fjords better serves predictive modelling of the fate of the Greenland Ice Sheet.

Preeclampsia (PE) is a pregnancy syndrome characterized by a systemic inflammatory response, and endogenous activation of monocytes. This study aimed to determine whether the activation of monocytes from preeclamptic women might interfere with the response to lipopolysaccharide (LPS)-in vitro stimulation. Fifty-two preeclamptic women and 32 normotensive (NT) pregnant women were included. Monocytes from peripheral blood were cultured with or without LPS. TLR4 expression was analyzed by flow cytometry, NF-κB activity was determined in nuclear extracts and cytokines production was evaluated by ELISA. Endogenous TLR4 ligands such as Hyaluronan, HMGB1 and Hsp70 were determined in plasma. The endogenous TLR4 expression and activation of NF-κB were statistically higher in monocytes from women with PE compared to NT group. Early-onset PE showed higher TLR4 expression compared to late-onset PE. Plasma levels of Hyaluronan, HMGB1, and Hsp70, as well as endogenous production of inflammatory cytokines, were elevated whilst lower production of IL-10 was observed in the PE group. After culture with LPS, monocytes presented lower NF-κB activation, TNF-α and IL-12 production in PE groups than in the NT group. The study demonstrates endogenous activation of monocytes from preeclamptic women, accompanied by higher expression of TLR4, NF-κB activation and elevated production of pro-inflammatory cytokines. The higher plasma levels of the TLR4 ligands hyaluronan, HMGB1 and hsp70, as well as the high concentration of TNF-α endogenously produced by monocytes, could induce the LPS tolerance phenomenon in these cells. These results suggest that monocytes play an important role in the maternal excessive systemic inflammatory response in PE., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: Many patients with pulmonary embolism (PE) report dyspnea on exertion following long-term treatment. Increased physiological dead space proportion (V D /V T ) and decreased cardiac stroke volume reserve may distinguish persistent effects of PE itself from symptoms reflecting comorbid conditions or deconditioning., Methods: This retrospective study analyzed a consecutive series of incremental symptom-limited cardiopulmonary exercise tests that had been ordered to evaluate persistent dyspnea on exertion following long-term treatment for acute PE. Physiological V D /V T was determined at anaerobic threshold from exhaled CO 2 and transcutaneous Pco 2 (validated against Paco 2 measurements). Cardiac stroke volume reserve was estimated at rest and at anaerobic threshold by using oxygen consumption/pulse and previously validated estimates of the arteriovenous oxygen content difference., Results: Cardiopulmonary exercise tests were performed on 40 patients with post-PE dyspnea. In 65.0% (95% CI, 50.2-79.8), V D /V T at anaerobic threshold was abnormally elevated, stroke volume reserve was decreased, or both defects occurred. V D /V T at anaerobic threshold was abnormally elevated (≥ 0.27) in 35.0% (95% CI, 20.2-49.8). V D /V T at anaerobic threshold significantly correlated with the extent of unmatched perfusion defects on subsequent ventilation-perfusion scans (P = .0085). In 55.0% (95% CI, 39.6-70.4), stroke volume reserve at anaerobic threshold was abnormally decreased (≤ 128% of the resting value). Both defects were present in 25.0% (95% CI, 11.6-38.4)., Conclusions: Increased V D /V T at anaerobic threshold and decreased stroke volume reserve during exercise are common among patients with dyspnea on exertion after long-term treatment of PE. The defects can be disclosed noninvasively by using cardiopulmonary exercise testing., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: Coronary artery geometry can have a significant impact in the hemodynamic behavior of coronary blood flow, influencing atherosclerotic plaque formation. The present work focuses on, through a statistical study, the connection between several geometric parameters of the right coronary artery-ostium cross-sectional area, angles between the common trunk and the side-branches, tortuosity, curvature and cross-sectional area in each side-branch-and their influence on hemodynamic descriptors. Parameters such as low wall shear stress and local disturbed flow, which are associated with atherosclerosis formation, were analysed., Methods: Computed tomography images of ten healthy individuals were selected to reconstruct in vivo three-dimensional models of right coronary arteries. Blood flow was simulated through a compliant model with realistic boundary conditions. Calculated hemodynamic descriptors values were correlated with the geometric parameters using the Pearson correlation coefficient (r) and the p value., Results: The strongest correlations were found in the middle and distal segments of the right coronary artery. A decrease in the ostium area promotes a decrease in the WSS magnitude from the proximal to the distal segment (r = 0.82). Very strong correlations (r > 0.90) were achieved between geometric parameters (cross-sectional area, angle, tortuosity) of the right-ventricular branch and the wall shear stress magnitude in the middle and distal segments., Conclusions: Low values of tortuosity, smaller cross-sectional area and higher angle of the right-ventricular branch leads to a hemodynamic behavior more propitious to atherosclerosis formation, within the study cases. The right-ventricular branch seems to have the highest influence in the hemodynamic behavior of the right coronary artery.

The hemodynamics conditioned by coronary geometry may play an important role in the creation of a pro-atherogenic environment in specific locations of the coronary tree. The aim of this study is to identify how several geometric parameters of the left coronary artery - cross-section areas, proximal left anterior descending artery length, angles between the branches and the septum, curvature and tortuosity - can be related with hemodynamic descriptors, using a computational fluid-structure interaction method. It is widely accepted that the hemodynamic indicators play an important role in identifying possible pro-atherogenic locations. A statistical study, using Pearson correlation coefficient and P value, was performed for a population study of 8 normal human left coronary arteries presenting right-dominant circulation. Within the study cases, arteries with high caliber (r = 0.88), high angles LMS-LAD (r = 0.49), LAD-LCx (r = 0.57) and LAD-Septum (r = 0.52), and high tortuosity LMS-LCx (r = 0.63) were correlated with a hemodynamic behavior propitious to plaque formation in the left anterior descending artery. In contrast, high proximal left anterior descending artery length (r = -0.41), high angle LMS-LCx (r = -0.59), high tortuosity LMS-LAD (r = -0.56) and LAD-LCx (r = -0.55) and high curvature of LMS (r = -0.60) and LCx (r = -0.56) can lead to non-favorable hemodynamic conditions for atheroma formation. Graphical abstract.

Exposure to ultraviolet (UV) radiation blocks DNA replication and arrests cellular division in Escherichia coli. Restoration of chromosome replication involves nucleoid reorganization, which involves the participation of the recombination-catalyzing proteins RecA, RecO, RecR and RecN. In this work, we evaluated the influence of recN, uvrA and recJ gene mutations on post-irradiation nucleoid reorganization. We used isogenic E. coli strains that are defective for these genes to study post-irradiation kinetics of the nucleoid shape fractions using fluorescence microscopy. The results showed that in the wild-type strain, post-irradiation nucleoid reorganization occurs, which restores the nucleoid shape fractions in the cells to those observed prior to irradiation. First, the nucleoid condenses into the central area of the irradiated cell. Second, the nucleoid disperses along the cell. Third, the cell enters the chromosome replicative phase and cytokinesis. Escherichia coli cells with a recN mutation did not exhibit increased nucleoid condensation, but chromosome replication and cytokinesis occurred. In the uvrA and recJ strains, the condensation step was delayed compared to the wild-type strain, and chromosome replication and cytokinesis did not occur. The results are discussed with an emphasis on the functions of RecN, UvrA and RecJ in nucleoid reorganization in UV-irradiated E. coli cells.

The definition of a suitable mesh to simulate blood flow in the human carotid bifurcation has been investigated. In this research, a novel mesh generation method is proposed: hexahedral cells at the center of the vessel and a fine grid of tetrahedral cells near the artery wall, in order to correctly simulate the large blood velocity gradients associated with specific locations. The selected numerical examples to show the pertinence of the novel generation method are supported by carotid ultrasound image data of a patient-specific case. Doppler systolic blood velocities measured during ultrasound examination are compared with simulated velocities using 4 different combinations of hexahedral and tetrahedral meshes and different fluid dynamic simulators. The Lin's test was applied to show the concordance of the results. Wall shear stress-based descriptors and localized normalized helicity descriptor emphasize the performance of the new method. Another feature is the reduced computation time required by the developed methodology. With the accurate combined mesh, different flow rate partitions, between the internal carotid artery and external carotid artery, were studied. The overall effect of the partitions is mainly in the blood flow patterns and in the hot-spot modulation of atherosclerosis-susceptible regions, rather than in their distribution along the bifurcation., (Copyright © 2018 John Wiley & Sons, Ltd.)

The information in this protocol covers from the basic steps and material necessary to start a sand fly colony up to the specific details which are important to the success of a Nyssomyia neivai colony. The greatest problems in our colony of Ny. neivai were solved with specific care, for instance, using vermiculite and an adequate number of adults in oviposition containers; the control of fungus with the exact amount of diet for the larvae and humidity control; a second blood meal for females and control of the number of times animals are used for blood meals. Currently, our colony is at F22 generation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Sand flies are natural hosts of various microorganisms. Due to their epidemiological importance, sand fly colonies are kept in laboratories to be studied in terms of their biology and vector/host/parasite interactions. In order to investigate the presence of oviposition pheromones in Nyssomyia neivai, experiments using Solid Phase Microextraction (SPME) were performed. However, siloxanes which is an external class of contamination, present in breeding containers made by plaster used to maintain sand flies in colonies, may be hindered the experiments., (Published by Elsevier B.V.)

Objective: Preeclampsia is a specific disorder of human pregnancy that is associated with hyperuricemia and higher levels of pro-inflammatory cytokines. Adenosine deaminase (ADA) is an enzyme present in all human tissues, and is considered an indicator of cellular inflammation. In the present study we assess whether adenosine deaminase (ADA) activity is altered in women with preeclampsia (PE) and contributes to elevated levels of uric acid and pro-inflammatory cytokine production., Study Design: The population studied consisted of 60 women with PE, 30 normotensive pregnant women (NT) and 20 non-pregnant women (NP). Uric acid concentration and ADA activity were determined in the serum. Peripheral blood mononuclear cells (PBMCs) were isolated and evaluated for intracellular nuclear transcription factor kappa B (NF-κB) levels and for endogenous tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production. The data were evaluated with parametric or non-parametric tests with significance set at P<0.05., Results: ADA levels were higher in the PE group compared with the NT and NP groups (P<0.001). A positive correlation between ADA and uric acid levels was identified in women with PE (P<0.001). Endogenous production of IL-1β and TNF-α, as well as intracellular NF-κB levels, were higher in PBMCs from the PE group than from NT and NP women (P<0.01) and correlated with the ADA concentration in preeclamptic women (P<0.01)., Conclusion: An elevation in ADA activity in women with PE may contribute to their increased levels of uric acid and pro-inflammatory immune activity., (Copyright © 2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Purpose: There is nowadays extensive experimental and computational investigation on the pathophysiology of atherosclerosis, searching correlations between its focal nature and local hemodynamic environment. The goal of this work is to present a methodology for patient-specific hemodynamics study of the carotid artery bifurcation based on the use of ultrasound (US) morphological and blood flow velocity patient data., Materials/methods: Subject-specific studies were performed for two patients, using a developed finite element code. Geometrical models were obtained from the acquisition of longitudinal and sequential cross-sectional ultrasound images and boundary conditions from Doppler velocity measurements at the common carotid artery., Results: There was a good agreement between ultrasound imaging data and computational simulated results. For a normal and a stenosed carotid bifurcation the velocity, wall shear stress (WSS) and WSS descriptors analysis illustrated the extremely complex hemodynamic behavior along the cardiac cycle. Different patterns were found, associated with morphology and hemodynamic patient-specific conditions. High values of time-averaged WSS (TAWSS) were found at stenosis site and for both patients TAWSS fields presented low values within areas of high oscillating shear index and relative residence time values, corresponding to recirculation zones., Conclusion: Simulated hemodynamic parameters were able to capture the disturbed flow conditions in a normal and a stenosed carotid artery bifurcation, which play an important role in the development of local atherosclerotic plaques. Computational simulations based on clinic US might help improving diagnostic and treatment management of carotid atherosclerosis., (Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Background: The most critical phase in sand fly colonization is the high mortality in the larval instars. In this study, we sought out strategies for improving the colonization of Nyssomyia neivai, one of the vectors of cutaneous leishmaniasis agent in South America., Methods: A colony of Ny. neivai was established in the laboratory from a field population, and the productivity of adults was evaluated considering carrying capacity, diet for larvae and surface for oviposition., Results: The highest emergency rate of adults was achieved with the fewest couples inside 150 mL rearing chambers on a sterilized diet made of rabbit feces, rabbit food, soil and fish food and with vermiculite as a substrate for oviposition and the development of larvae., Conclusion: Our data on Ny. neivai colonization showed that the best adult productivities were achieved with fewer couples inside the rearing chambers; smaller rearing containers of 150 mL (due to less fungi growth); sterilized diet made of rabbit feces, rabbit food, soil and fish food; and vermiculite as the substrate for oviposition and development of larvae.

The ability of using non-expensive ultrasound (US) image data together with computer fluid simulation to access various severities of carotid stenosis was inquired in this study. Subject-specific hemodynamic conditions were simulated using a developed finite element solver. Individual structured meshing of the common carotid artery (CCA) bifurcation was built from segmented longitudinal and cross-sectional US images; imposed boundary velocities were based on Doppler US measurements. Simulated hemodynamic parameters such as velocities, wall shear stress (WSS) and derived descriptors were able to predict disturbed flow conditions which play an important role in the development of local atherosclerotic plaques. Hemodynamic features from six individual CCA bifurcations were analyzed. High values of time-averaged WSS (TAWSS) were found at stenosis site. Low values of TAWSS were found at the bulb and at the carotid internal and external branches depending on the particular features of each patient. High oscillating shear index and relative residence time values assigned highly disturbed flows at the same artery surface regions that correlate only moderately with low TAWSS results. Based on clinic US examinations, results provide estimates of flow changes and forces at the carotid artery wall toward the link between hemodynamic behavior and stenosis pathophysiology.

Problem: This study evaluated whether the monocyte inflammatory state in pre-eclampsia (PE) might be associated with polarization to either M1 classically or M2 alternatively activated monocyte subsets., Method of Study: Eighty-five women with (PE) and 52 normotensive (NT) pregnant women matched for gestational age were included. Expression of surface receptors characteristic of M1, such as Toll-like receptor (TLR)2, TLR4, and CD64, or M2, such as CD163 and CD206 monocyte subsets were evaluated in peripheral blood monocytes by flow cytometry. Tumour necrosis factor-alpha (TNF-α), interleukin-(IL)-12p40, IL-12p70, and IL-10 were evaluated in the supernatant of monocyte cultures by ELISA., Results: Expression of TLR4 and CD64 by monocytes from pre-eclamptic women was significantly higher, while the expression of CD163 and CD206 expression was significantly lower compared with NT pregnant women. Endogenous production of TNF-α, IL-12p40, and IL-12p70 by monocytes was increased, while synthesis of IL-10 was lower in women with PE than in NT pregnant women., Conclusions: Monocytes from women with PE are classically activated, producing higher levels of pro-inflammatory cytokines, and express surface receptors characteristic of the M1 subset. These results provide evidence that the systemic inflammatory environment in PE may differentiate and polarize these cells to the M1 phenotype., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Preeclampsia (PE), a specific syndrome of pregnancy, can be classified into early and late onset, depending on whether clinical manifestations occur before or after 34 weeks' gestation. We determined whether plasma concentrations of Hsp60 and Hsp70 were related to circulating cytokine levels, as well as kidney and liver functions, in early- and late-onset PE. Two hundred and thirty-seven preeclamptic women (95 with early- and 142 with late-onset PE) were evaluated. Plasma levels of Hsp60, Hsp70, and their specific antibodies, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-10, IL-12, and soluble TNF-α-receptor I (sTNFRI) concentrations, were determined by enzyme-linked immunosorbent assay (ELISA). Concentrations of Hsp70, TNF-α, IL-1β, IL-12, and sTNFRI were significantly elevated in patients with early-onset PE compared with women with late-onset PE; IL-10 levels were significantly lower in the early-onset PE group. Concentrations of urea, uric acid, proteinuria, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and lactate dehydrogenase (LDH) were also significantly higher in early-onset PE. The percentage of infants with intrauterine growth restriction was also significantly higher in women with early-onset PE. There were positive correlations between Hsp70 levels and TNF-α, TNFRI, IL-1β, IL-12, GOT, GPT, LDH, and uric acid concentrations in early-onset PE group. Thus, early-onset PE was associated with greater maternal and fetal impairment. There are differences in pathophysiology between early- and late-onset PE, highlighting by the difference in Hsp70 levels., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Silibinin is a polyphenolic plant flavonoid with anti-inflammatory properties. The present study investigated the effect of silibinin on oxidative metabolism and cytokine production - tumor necrosis factor-alpha (TNF-α), interleukin (IL)12, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, IL-10, and transforming growth factor beta (TGF-β1) - by peripheral blood monocytes (PBM) from preeclamptic pregnant women. It is a case-controlled study involving women with preeclampsia (PE, n = 30) compared with normotensive pregnant (NT, n = 30) and with non-pregnant (NP, n = 30) women. Monocytes were obtained and cultured with or without silibinin (5 μM or 50 μM) for 18 h. Superoxide anion (O2-) and hydrogen peroxide (H2O2) release were determined by specific assays, and cytokine levels were determined by immunoenzymatic assays (ELISA). Monocytes from preeclamptic women cultured without stimulus released higher levels of O22, H2O2 and TNF-α, and lower levels of IL-10 and TGF-β1 than did monocytes from NT and NP women. Treatment in vitro with silibinin significantly inhibited spontaneous O2- and H2O2 release and TNF-α production by monocytes from preeclamptic women. The main effect of silibinin was obtained at 50 μM concentration. Thus, silibinin exerts anti-oxidative and anti-inflammatory effects on monocytes from preeclamptic pregnant women by inhibiting the in vitro endogenous release of reactive oxygen species and TNF-α production.

In medical practice, bypass grafts are commonly used as an alternative route around strongly stenosed or occluded arteries. In contrast to arterial bifurcations, surgically created anastomosis can be modified with the objective of enabling optimal graft geometry to yield a flow environment that improves its longevity. This paper presents a three dimensional numerical study of blood flow through bypass systems with different geometries. Coupled with the finite element solver a shape optimization framework considering a genetic algorithm is presented. Numerical results show the benefits of understanding blood flow hemodynamic at anastomosis junctions achieving design improvements. Minimizing recirculation zones and flow stagnation can be useful in surgical planning., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Preeclampsia (PE) is a complication of human pregnancy associated with an intense inflammatory response involving leukocyte activation, as well as elevated production of pro-inflammatory cytokines. The nuclear transcription factor-kappa B (NF-κB) is present in cells of the immune system and is responsible for transcription of genes coding for pro-inflammatory proteins. Silibinin is the main component of silymarin, a polyphenolic extract obtained from fruits and seeds of Silybum marianum with potent hepatoprotective and anti-inflammatory activities. In this study, we assessed whether silibinin modulated NF-κB activity and the production of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMCs) from preeclamptic patients. PBMC from women with PE, normotensive (NT) pregnant women, and nonpregnant (NP) women were cultured with or without silibinin (5 μM and 50 μM) and 1 μg/mL lipopolysaccharide (LPS) for 18 h. The supernatants were assayed for tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) by ELISA. Cells were cultured for 30 min to evaluate NF-κB activity. There was increased endogenous activation of NF-κB as well as TNF-α and IL-1β release by PBMC in the PE group compared with the NT and NP groups. A positive correlation between NF-κB activity and cytokine production was also observed in the PE group. Silibinin was capable of reducing, at least in part, the levels of NF-κB and cytokines TNF-α and IL-1β in preeclamptic women. We conclude that silibinin exhibits potent anti-inflammatory activity on PBMC from preeclamptic women by downmodulation of NF-κB activation and inflammatory cytokine production., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Hyperuricemia is a common finding in preeclamptic pregnancies and proteinuria, as well as hypertension are markers of preeclampsia. Production of anti-angiogenic proteins seems to be involved in the pathophysiology of hypertension and proteinuria in preeclampsia., Objectives: The purpose of this study was to evaluate whether there is an association between renal function and changes in serum levels of angiogenic factors in preeclamptic patients., Methods: Serum was obtained from 83 preeclamptic patients in the last trimester of pregnancy for determination of uric acid. Placental growth factor (PlGF), vascular endothelial growth factor (VEGF) and soluble form of vascular endothelial growth factor receptor (sVEGFR-1) were evaluated in serum by an enzyme immunoassay. Proteinuria was determined in a 24-h urine collection. The concentration of angiogenic factors was compared with serum uric acid levels (<6mg/dL vs ⩾6mg/dL) and with proteinuria levels (<2g vs ⩾2g). Statistical analysis was performed using non-parametric tests with significance level set at 5%., Results: In 40% of women with preeclampsia serum uric acid levels were ⩾6mg/dL, and proteinuria concentration ⩾2g was detected in 41% of patients. Positive correlation was observed between uric acid and proteinuria levels (r=0.7274; p<0.0001). Serum levels of PIGF were significantly lower in preeclamptic women with serum uric acid level ⩾6mg/dL compared with women with serum uric acid <6mg/dL (median 48.46 vs 117.32pg/mL). Significant difference between proteinuria ⩾2g and <2g was detected in relation to serum levels of PIGF (median 47.58 vs 114.24pg/mL), VEGF (median 25.35 vs 33.74pg/mL) and sVEGFR-1 (median 5386 vs 4605pg/mL)., Conclusion: Elevation in circulating uric acid as well as proteinuria in preeclamptic women is associated with an altered angiogenic balance, suggesting that angiogenic factors may be involved in kidney dysfunction., (Copyright © 2010. Published by Elsevier B.V.)

Introduction: Pre-eclampsia (PE) is a complication of human pregnancy characterized by hypertension and proteinuria after 20 weeks of gestation. In addition to increased activation of monocytes and granulocytes, there is an elevated production of proinflammatory cytokines in pregnant women with PE. The nuclear transcription factor-kB (NF-kB) is present in the cells of the immune system and is responsible for transcription of genes related to inflammation. Whereas the PE is associated with intense inflammatory response, the use of substances modulating the activity of NF-kB factor could be useful in alleviating the inflammation present in these patients. Silibinin is the main component of silymarin, a polyphenolic extract obtained from fruits and seeds of Sylibum marianum with potent hepatoprotective, anti-inflammatory and anti-fibrotic activities., Objectives: The objective of this study was to assess whether silibinin modulates the activity of NF-kB and the production of inflammatory cytokines by mononuclear cells of patients with PE., Methods: We evaluated 34 pregnant women with PE, 20 normotensive pregnant women (NT) and 15 non-pregnant women (NP). Mononuclear cells (PBMC) were obtained from peripheral blood and cultured in the presence or absence of silibinin (50uM) and stimulated with 1ug/mL of lipopolysaccharide (LPS) for 18h. The supernatant was employed for determination of tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1β) by enzyme immunoassay. The cells were also cultured for 30min to perform the extraction and determination of the nuclear activity of NF-kB., Results: The results showed increased endogenous activation of NF-kB in PBMC of the PE group compared with the NT and NP groups. We also observed increased production of TNF-α and IL-1β by non-stimulated PBMC in the PE group compared with NT and NP groups. A positive correlation between NF-kB activity and endogenous production of TNF-α (r=0.6509; p=0.0047) or IL-1 b (r=0.5106; p=0.0304) was observed in the PE group. Silibinin showed an anti-inflammatory activity by inhibiting the spontaneous and LPS-stimulated NF-kB activation as well as the production of inflammatory cytokines in all the groups studied., Conclusion: Patients with PE showed a greater activation of PBMC cells compared with NT women. Silibinin showed modulatory activity on the inflammatory response by downregulation of NF-kB activation as well as TNF-α and IL-10 production., Financial Support: FAPESP 2010/00776-0., (Copyright © 2012. Published by Elsevier B.V.)

Introduction: Toll-like receptor (TLR)-4 and TLR-2 are involved in inflammatory response of monocytes. These cells are activated in pregnant women with preeclampsia (PE), and over-produce inflammatory cytokines. TLR4 may recognize endogenous ligands, the so-called danger signals released by damaged cells, leading to production of pro-inflammatory cytokines., Objectives: This study investigated TLR2 and TLR4 expression and cytokine production by monocytes from women with PE before and after stimulation with TLR ligands., Methods: Monocytes (5×10(5)cell/mL) were obtained from 32 preeclamptic (PE) and 20 normotensive (NT) pregnant women in the last trimester of pregnancy. TLR2 and TLR4 expression on monocyte surface was determined by flow cytometry in non-stimulated cells, and after 18h of culture with lipopysaccharide (LPS) and peptidoglycan (PG). TNF-α, IL-10 and IL-12p70 production by these cells stimulated or not with LPS or PG was evaluated by enzyme immunoassay. Results were analyzed by non-parametric tests with significance level set at 5%., Results: In the absence of stimulation, the basal TLR4 expression by monocytes detected by the median fluorescence intensity (MFI) was significantly higher in the PE group than in the NT group while no significant differences were observed between groups in relation to endogenous TLR2 expression. An increase in TLR4 MFIs was detected after monocytes from NT pregnant women were stimulated with LPS while TLR2 expression was increased after PG-stimulation. No alterations in TLR expression was detected after LPS or PG-stimulation in monocytes from patients with PE. Evaluation of endogenous cytokine levels in supernatant culture of monocytes showed higher concentrations of TNF-α and IL-12p70 in preeclamptic women in comparison with the NT group, whereas IL-10 values were significantly higher in NT pregnant women than in the PE group. In contrast, when monocytes were stimulated with the TLRs ligands LPS and PG, the release of TNF-α was significantly reduced, while IL-12p70 levels were significantly higher in women with PE compared to NT group. IL-10 production was similar in both groups studied., Conclusion: The basal up-regulation of TLR4 expression associated with endogenous high TNF-α and IL-12p70 production by monocytes from preeclamptic women confirms the activated profile of these cells by the disease process. These findings provide new insights into possible roles for TLRs in the pathogenesis of systemic inflammation detected in PE., Financial Support: FAPESP 2009/11924-3 and 2010/20207-0., (Copyright © 2012. Published by Elsevier B.V.)

Introduction: Monocytes from peripheral blood of pregnant women with preeclampsia are endogenously activated and secrete high levels of free radicals and inflammatory cytokines., Objectives: This study aimed at evaluating whether the inflammatory state of monocytes observed in preeclampsia is associated with the polarization of monocyte to M1 profile in peripheral blood, correlating the expression of surface receptors CD64, TLR2, TLR4, and CD163 and CD206 with cytokine production., Methods: We studied 90 pregnant women, 30 normotensive and 60 with preeclampsia, matched for gestational age. Peripheral blood monocytes obtained from normotensive pregnant or preeclamptic pregnant women were cultured for 18h, and the expression of surface receptors on M1 inflammatory monocyte subpopulation (TLR2, TLR4 and CD64) and M2 suppressor monocyte subpopulation (CD163 and CD206) were evaluated by flow cytometry, using specific monoclonal antibodies, labeled with fluorochromes. The values were expressed as ??the mean fluorescence intensity. Moreover, the production of proinflammatory cytokines associated with M1 profile (TNF-α, IL-12p70 and IL-23) and the anti-inflammatory cytokine associated with M2 profile (IL-10) were evaluated in the monocyte supernatant of culture by enzyme immunoassay. Results were analyzed using nonparametric tests with significance level set at 5%., Results: The expression of CD4 and TLR4 on monocyte surface, from women with preeclampsia was significantly higher, while the expression of CD163 and CD206 was significantly decreased compared with normotensive pregnant women, suggesting the predominance of monocyte M1 profile. Endogenous production of TNF-α, IL-12p70 and IL-23 by monocytes was increased, while synthesis of IL-10 was lower in women with preeclampsia compared with normotensive pregnant women. Positive correlations between TLR4 and CD64 (r=0.5849), TLR4 and TNF-α (r=0.5126) or TLR4 and IL-23 (r=0.8095), as well as between CD64 and TNF-α (r = 0.7133) or CD64 and IL-23 (r = 0.6051) were observed in the preeclamptic group. The results confirm the activated state of monocytes from women with preeclampsia by increased production of proinflammatory cytokines and the expression of receptors characteristic of the M1 subpopulation., Conclusion: This study provides evidence that monocytes from women with preeclampsia are classically activated and the systemic inflammatory environment may differentiate and polarize these cells to the M1 profile., Financial Support: CNPq, FAPESP 2009/11924-3 and 2010/20207-0., (Copyright © 2012. Published by Elsevier B.V.)

Introduction: Preeclampsia is a human pregnancy-specific syndrome characterized by the onset of hypertension and proteinuria. These manifestations may occur before the 34th week of gestation or from this period on, being denominated early-onset or late-onset preeclampsia respectively. The etiology of both disorders seems to differ qualitatively; therefore, different strategies of prevention and treatment must be studied., Objectives: The aim of the present study is to determine whether the plasma levels of heat-shock proteins Hsp60 and Hsp70 as well as specific antibodies anti-Hsp60 and anti-Hsp70 may differentiate early-onset from late-onset preeclampsia., Methods: We evaluated 175 pregnant women with PE (55 early-onset PE and 120 late-onset PE). Plasma was obtained from peripheral blood and Hsp60, Hsp70 as well as anti-Hsp60 and anti-Hsp70 antibody levels were determined by enzyme immunoassay. Uric acid levels were also determined in the plasma of patients. For statistical analyses, the Mann-Whitney U-test and the Spearman rank order correlation were applied with significance level set at 5%., Results: Hsp70 levels obtained from early-onset PE group were significantly higher than the late-onset PE women and showed positive correlation with uric acid (r=0.4547; p=0.0028). The Hsp60 production was similar in both groups. Our results also indicate that there was no significant difference of anti-Hsp60 and anti-Hsp70 antibody levels between women with early- and late-onset PE. However,these antibody levels were high,indicating a strong relationship with the production of HSP60 and Hsp70 protein., Conclusion: Association between levels of Hsp70 and uric acid in plasma of patients with early-onset PE seems to reflect the oxidative stress in this group of patients. This study provides evidence that Hsp70 determination may be utilized to assess the differentiation between early- and late-onset PE., Financial Support: FAPESP 2010/09241-2., (Copyright © 2012. Published by Elsevier B.V.)

Unlabelled: The harmony of the facial profile is widely influenced by the height and form of the nasal dorsum. A few millimeters can make the lateral view aesthetically more or less pleasing and adequate in a subject's face. Professionals working with facial aesthetics should focus not only on the surgical techniques for proposed outcomes, but also with the subtleties and subjectivity that characterize aesthetic concepts and judgment., Material and Methods: A prospective survey to evaluate the preferences of a group of healthcare professionals working with facial aesthetics, a group of fine artists, and lay people about the best nasal radix height; the survey involved comparing 3 different nasal radix heights using computer-altered photographs of women with measurements close to the Caucasian standard., Results and Conclusion: The lowest position of the nasal radix--close to the height of the pupil--was preferred (53%), followed by the middle position (superior crease of the eye). The highest position, resembling classic Greek statues, was considered the worst. The authors evaluated the effect of age, gender, and educational level on the choice of the best and worst female profiles.

Plants have contributed over the years to the discovery of various pharmacological products. Amongst the enormous diversity of herbs with remarkable medicinal use and further pharmacological potential, here in this report we evaluated pulp extracts from Eugenia dysenterica fruits and further identified the active principle involved in such laxative activity in rats. For protein isolation, fruits were macerated with an extraction solution following precipitation with (NH(4))(2)SO(4) (100%). After dialysis, the peptide was applied onto a reversed-phase semi-preparative HPLC column, and the major fraction was eluted with 26% and 66% acetonitrile. The evaluation of molecular masses by MALDI-TOF and Tris/Tricine SDS-PAGE of HPLC fractions showed the presence of a major peptide with approximately 7 kDa. The N-terminal amino acid peptide sequence was determined and showed no similarity to other proteins deposited in the Data Bank. Peptide from E. dysenterica was able to enhance rats' intestinal motility by approximately 20.8%, probably being responsible for laxative activity. Moreover, these proteins were non-toxic to mammals, as observed in histopathology and hemolytic analyses. In conclusion, results here reported indicate that, in the near future, proteins synthesized by E. dysenterica fruits could be utilized in the development of novel biotechnological pharmaceutics with laxative properties for use in chronic constipation and irritable bowel syndrome treatment., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: To assess the impact of zinc supplementation on nutritional and biochemical parameters among children aged 12 to 59 months., Methods: A blinded randomized clinical trial was carried out with 58 children aged 12 to 59 months included in the Programa Governamental de Combate a Carências Nutricionais (National Child Nutritional Program), which provided them with 2 kg of iron-fortified milk. The supplementation group (n = 28) received 10 mg/day of zinc sulfate for four months, and the control group (n = 30) received placebo. The following parameters were used to assess the nutritional status: weight-for-height and height-for-age expressed as z scores, according to National Center for Health Statistics (NCHS) standards, biochemical measurements of serum iron and serum zinc, and hemoglobin and hematocrit levels., Results: Zinc supplementation did not have a remarkable influence on anthropometric parameters. Baseline serum zinc levels were low in both groups. After supplementation, variations in mean hemoglobin (p = 0.002), hematocrit (p = 0.001), serum zinc (p = 0.023), and serum iron (p = 0.013) levels significantly increased in the zinc supplementation group., Conclusion: Zinc supplementation improved hemoglobin response and normalized serum zinc concentration. The results show the importance of establishing policies for nutritional care that can tackle zinc deficiency as well.