X-ray free electron lasers deliver photon pulses that are bright enough to observe diffraction from extremely small crystals at a time scale that outruns their destruction. As crystals are ...continuously replaced, this technique is termed serial femtosecond crystallography (SFX). Due to its high pulse repetition rate, the European XFEL enables the collection of rich and extensive data sets, which are suited to study various scientific problems, including ultra-fast processes. The enormous data rate, data complexity, and the nature of the pixelized multimodular area detectors at the European XFEL pose severe challenges to users. To streamline the analysis of the SFX data, we developed the semiautomated pipeline EXtra-Xwiz around the established CrystFEL program suite, thereby processing diffraction patterns on detector frames into structure factors. Here we present EXtra-Xwiz, and we introduce its architecture and use by means of a tutorial. Future plans for its development and expansion are also discussed.
Leishmaniasis is a neglected tropical disease caused by Leishmania species. Available therapeutic options have several limitations. The drive to develop new, more potent, and selective ...antileishmanial agents is thus a major goal. Herein we report the synthesis and the biological activity evaluation against promastigote and amastigote forms of Leishmania amazonensis of nine 4,8-dimethoxynaphthalenyl chalcones. Compound ((E)-1-(4,8-dimethoxynaphthalen-1-yl)-3-(4-nitrophenyl)prop-2-en-1-one), 4f, was the most promising with an IC50 = 3.3 ± 0.34 μM (promastigotes), a low cytotoxicity profile (CC50 = 372.9 ± 0.04 μM), and a high selectivity index (SI = 112.6). Furthermore, 4f induced several morphological and ultrastructural changes in the free promastigote forms, loss of plasma membrane integrity, and increased reactive oxygen species (ROS). An in silico analysis of drug-likeness and ADME parameters suggested high oral bioavailability and intestinal absorption. Compound 4f reduced the number of infected macrophages and the number of amastigotes per macrophage, with an IC50 value of 18.5 ± 1.19 μM. Molecular docking studies with targets, ARG and TR, showed that compound 4f had more hydrogen bond interactions with the ARG enzyme, indicating a more stable protein-ligand binding. These results suggest that 4,8-dimethoxynaphthalenyl chalcones are worthy of further study as potential antileishmanial drugs.
Although acute gastroenteritis (AGE) has been reported as a common infectious disease in children, there is scarce information about enterovirus (EV) circulating associated with AGE cases in Brazil. ...The purpose of the present study was to identify and characterize the enteroviruses associated with AGE in children in Belém, Brazil. A total of 175 stool samples were obtained from children hospitalized revealing the presence of EV in 26.3% (46/175) of infections. EV type was identified in 78.3% (36/46) and EV-B species (61.1%; 22/36) was the most prevalent EV-detected followed by EV-C (25%; 9/36) and EV-A (13.9%; 5/36). This study has provided important information about the enterovirus circulation in Pará state, Northern Brazil.
In the current investigation, fecal material was obtained during a community‐based longitudinal study conducted from 1983 to 1986. This study consisted of 71 children aged newborn to 3 years. A total ...of 216 samples from three of these children were screened by real‐time quantitative polymerase chain reaction (RT‐qPCR) for the presence of enteroviruses, and positive samples were serotyped by VP1 and VP3 sequencing of the viral genome. Of these, 12 (5.6%) came from symptomatic cases, and the remaining asymptomatic cases were collected fortnightly during the 3 years of study. A positivity of 63.4% (137/216) was obtained by RT‐qPCR, with 58.3% (7/12) in relation to the symptomatic group and 63.7% (130/204) in relation to the asymptomatic group. The 137 positive samples were inoculated into the RD, HEp2C, and L20B cell lines, and the cytopathic effect was observed in 37.2% (51/137) samples. It was also possible to identify 40.9% (56/137), between isolated (n = 46) and nonisolated (n = 10). Enterovirus serotype diversity (n = 25) was identified in this study, with the predominant species being B (80.3%), followed by C (16.1%) and A (3.6%). Cases of reinfection by different serotypes were also observed in the three children studied. Analyses involving different age groups of these minors confirmed that the most affected age was between 12 to 24 months, with a prevalence of 77.6% (52/67). The enterovirus (EV) circulated in the 3 years of research, showed peaks in some months, without defined seasonality. This study demonstrated a high circulation and serotype diversity of EV in fecal samples, collected over 30 years ago. This endorsed the evaluation of important points of the epidemiology of these viruses, such as the presence of coinfection and reinfection of the same individual by different circulating serotypes. Understanding the frequency and duration of EV infections is important in determining their association with persistent diarrhea.
Highlights
High detection rate of enteroviruses in children followed from birth to 3 years of age.
Unprecedented research for this virus, considering the period for comparative analysis.
Phylogenetic analysis of nucleotide sequences allowed for accurate classification of enteroviruses variants.
The co-circulation of types of arbovirus in areas where they are endemic increased the risk of outbreaks and limited the diagnostic methods available. Here, we analyze the epidemiological profile of ...DENV, CHIKV and ZIKV at the serological and molecular level in patients with suspected infection with these arboviruses in the city of Juazeiro do Norte, Ceará, Brazil. In 2016, the Central Public Health Laboratory (LACEN) of Juazeiro do Norte received 182 plasma samples from patients who visited health facilities with symptoms compatible with arbovirus infection. The LACEN performed serological tests for detection of IgM/IgG to DENV and CHIKV. They then sent these samples to the Retrovirology Laboratory of the Federal University of São Paulo and Faculty of Medical of the ABC where molecular analyses to confirm the infection by DENV, ZIKV and CHIKV were performed. The prevalence of IgM/IgG antibodies and of infections confirmed by RT-qPCR were presented with 95% confidence interval. In serologic analysis, 125 samples were positive for antibodies against CHIKV and all were positive for antibodies against DENV. A higher prevalence of IgG against CHIKV (63.20% with 95% CI: 45.76-70.56) than against DENV (95.05% with 95% CI: 78.09-98.12) was observed. When the samples were submitted to analysis by RT-qPCR, we observed the following prevalence: mono-infection by ZIKV of 19.23% (95% CI: 14.29-34.82) patients, mono-infection by CHIKV of 3.84% (95% CI: 2.01-5.44) and co-infection with ZIKV and CHIKV of 1.09% (95% CI: 0.89-4.56). The serologic and molecular tests performed in this study were effective in analyzing the epidemiological profile of DENV, CHIKV and ZIKV in patients with suspected infection by these arboviruses in the city of Juazeiro do Norte, Ceará/Brazil.
Abstract
On the detection and identification of enteroviruses circulating in children with acute gastroenteritis in Brazil: reply to Luchs, A. Comments on Detection and identification of ...enteroviruses circulating in children with acute gastroenteritis in Pará State, Northern Brazil (2010–2011).
Augmented reality (AR) uses the real-world setting but enables a person to interact with virtual objects. In this study, we aimed to explore the use of alphabet letter and number in an AR task and ...its influence in reaction time in a population with autism spectrum disorders (ASD) compared with the performance of typical developing (TD) controls. We evaluated reaction time before and after AR tasks that consisted of identifying correct numbers and alphabet letters in 48 people with ASD and 48 with TD controls. Results indicate that total points for TD group were higher (
= 86.4 and
= 79.0) when compared with the ASD group (
= 54.5 and
= 51.5) for alphabet letters and numbers, respectively. Moreover, in analysis of reaction time results, only the ASD group showed an improvement in performance after the practice of an AR task. The control group was faster before (
= 553.7) and after (
= 560.5) when compared with the ASD group (
= 2616.0 and
= 2374.6, respectively). Despite the need for further studies, our results support that there is potential for clinical use of an AR task-based intervention for people with ASD.
Summary While administration of medical aerosols with heliox and positive airway pressure are both used clinically to improve aerosol delivery, few studies have differentiated their separate roles in ...treatment of asthmatics. The aim of this randomized, double blinded study is to differentiate the effect of heliox and oxygen with and without positive expiratory pressure (PEP), on delivery of radiotagged inhaled bronchodilators on pulmonary function and deposition in asthmatics. 32 patients between 18 and 65 years of age diagnosed with stable moderate to severe asthma were randomly assigned into four groups: (1) Heliox + PEP ( n = 6), (2) Oxygen + PEP ( n = 6), (3) Heliox ( n = 11) and (4) Oxygen without PEP ( n = 9). Each group received 1 mg of fenoterol and 2 mg of ipratropium bromide combined with 25 mCi (955 Mbq) of Technetium-99m and 0.9% saline to a total dose volume of 3 mL placed in a Venticis® II nebulizer attached to a closed, valved mask with PEP of 0 or 10 cm H2O. Both gas type and PEP level were blinded to the investigators. Images were acquired with a single-head scintillation camera with the longitudinal and transverse division of the right lung as regions of interest (ROIs). While all groups responded to bronchodilators, only group 1 showed increase in FEV1 %predicted and IC compared to the other groups ( p < 0.04). When evaluating the ROI in the vertical gradient we observed higher deposition in the middle and lower third in groups 1 ( p = 0.02) and 2 ( p = 0.01) compared to group 3. In the horizontal gradient, a higher deposition in the central region in groups 1 ( p = 0.03) and 2 ( p = 0.02) compared to group 3 and intermediate region of group 2 compared to group 3. We conclude that aerosol deposition was higher in groups with PEP independent of gas used, while bronchodilator response with Heliox + PEP improved FEV1 % and IC compared to administration with Oxygen, Oxygen with PEP and Heliox alone. Trial registration NCT01268462.
The European XFEL is a megahertz repetition-rate facility producing extremely bright and coherent pulses of a few tens of femtoseconds duration. The amount of data generated in the context of user ...experiments can exceed hundreds of gigabits per second, resulting in tens of petabytes stored every year. These rates and volumes pose significant challenges both for facilities and users thereof. In fact, if unaddressed, extraction and interpretation of scientific content will be hindered, and investment and operational costs will quickly become unsustainable. In this article, we outline challenges and solutions in data reduction.
In the nearly planar title compound (r.m.s. deviation for the 24 non-H atoms = 0.064 Å), C(18)H(16)ClN(3)O(2), the conformation about the N=C bond is E. Supra-molecular chains propagated by glide ...symmetry along 001 are found in the crystal packing. These are sustained by N-H⋯N hydrogen bonds with the quinoline N atom being the acceptor. The chains are connected into a three-dimensional architecture by π-π inter-actions involving all three aromatic rings centroid-centroid distances = 3.5650 (9)-3.6264 (9) Å.
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