750 research outputs found

    Respiratory Motion Correction in Dynamic PET with a Single Attenuation Map

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    In addition to static tracer uptake values used routinely in clinical facilities, PET imaging can provide useful information on tracer kinetics via the use of dynamic acquisitions where a set of time frames are acquired starting from the injection/inhalation of the radiotracer. In lung studies, kinetic parameters, estimated from compartmental modelling, are however affected by respiratory motion. When only one attenuation image is available, most existing motion compensation strategies are not appropriate for the initial short time frames, especially as the activity distribution changes rapidly over the early part of the dynamic acquisition. This work presents a preliminary study to handle respiratory motion using a two-step process that uses gated dynamic data as input. We first use joint reconstruction of activity and motion on the entire gated PET data to estimate deformation fields. This allows the subsequent reconstruction of each time frame separately with motion compensation. We present results comparing on one hand the compartment model fit residuals with and without respiratory motion compensation and on the other hand the diaphragm position in non-attenuation corrected images and from this method

    ATENA–A Novel Rapidly Manufactured Medical Invasive Ventilator Designed as a Response to the COVID-19 Pandemic: Testing Protocol, Safety, and Performance Validation

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    Background: The urgent need for mechanical ventilators to support respiratory insufficiency due to SARS-CoV-2 led to a worldwide effort to develop low-cost, easily assembled, and locally manufactured ventilators. The ATENA ventilator project was developed in a community-based approach targeting the development, prototyping, testing, and decentralized manufacturing of a new mechanical ventilator. Objective: This article aims to demonstrate ATENA's adequate performance and safety for clinical use. Material: ATENA is a low-cost ventilator that can be rapidly manufactured, easily assembled, and locally produced anywhere in the world. It was developed following the guidelines and requirements provided by European and International Regulatory Authorities (MHRA, ISO 86201) and National Authorities (INFARMED). The device was thoroughly tested using laboratory lung simulators and animal models. Results: The device meets all the regulatory requirements for pandemic ventilators. Additionally, the pre-clinical experiences demonstrated security and adequate ventilation and oxygenation, in vivo. Conclusion: The ATENA ventilator had a good performance in required tests in laboratory scenarios and pre-clinical studies. In a pandemic context, ATENA is perfectly suited for safely treating patients in need of mechanical ventilation.Financial support and sponsorship by CEiiA, INOV4COVID program, donations from scientific patronage, and commercial sales

    Red (660 nm) and infrared (830 nm) low-level laser therapy in skeletal muscle fatigue in humans: what is better?

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    In animal and clinical trials low-level laser therapy (LLLT) using red, infrared and mixed wavelengths has been shown to delay the development of skeletal muscle fatigue. However, the parameters employed in these studies do not allow a conclusion as to which wavelength range is better in delaying the development of skeletal muscle fatigue. With this perspective in mind, we compared the effects of red and infrared LLLT on skeletal muscle fatigue. A randomized double-blind placebo-controlled crossover trial was performed in ten healthy male volunteers. They were treated with active red LLLT, active infrared LLLT (660 or 830 nm, 50 mW, 17.85 W/cm2, 100 s irradiation per point, 5 J, 1,785 J/cm2 at each point irradiated, total 20 J irradiated per muscle) or an identical placebo LLLT at four points of the biceps brachii muscle for 3 min before exercise (voluntary isometric elbow flexion for 60 s). The mean peak force was significantly greater (p < 0.05) following red (12.14%) and infrared LLLT (14.49%) than following placebo LLLT, and the mean average force was also significantly greater (p < 0.05) following red (13.09%) and infrared LLLT (13.24%) than following placebo LLLT. There were no significant differences in mean average force or mean peak force between red and infrared LLLT. We conclude that both red than infrared LLLT are effective in delaying the development skeletal muscle fatigue and in enhancement of skeletal muscle performance. Further studies are needed to identify the specific mechanisms through which each wavelength acts

    Safety, immunogenicity, and transplacental antibody transport of conjugated and polysaccharide pneumococcal vaccines administered to pregnant women with HIV: a multicentre randomised controlled trial

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    Background: Pneumococcus remains an important cause of morbidity in pregnant women with HIV and their infants. We compared the safety and immunogenicity of PCV-10 and PPV-23 with placebo administered in pregnancy. Methods: This double-blind, multicentre, randomised controlled trial was done at eight outpatient clinics in Brazil. Eligible participants were adult women with HIV who were pregnant at a gestational age between 14 weeks and less than 34 weeks and who were taking antiretroviral therapy at study entry. Participants were randomly assigned (1:1:1) to receive either PCV-10, PPV-23, or placebo. Participants and study teams were unaware of treatment allocation. Antibodies against seven vaccine serotypes in PCV-10 and PPV-23 were measured by ELISA. The primary outcomes were maternal and infant safety assessed by the frequency of adverse events of grade 3 or higher; maternal seroresponse (defined as ≥2-fold increase in antibodies from baseline to 28 days after immunisation) against five or more serotypes; and infant seroprotection (defined as anti-pneumococcus antibody concentration of ≥0·35 μg/mL) against five or more serotypes at 8 weeks of life. The study was powered to detect differences of 20% or higher in the primary immunological outcomes between treatment groups. This trial is registered with ClinicalTrials.gov, NCT02717494. Findings: Between April 1, 2016, and Nov 30, 2017, we enrolled 347 pregnant women with HIV, of whom 116 were randomly assigned to the PCV-10 group, 115 to the PPV-23 group, and 116 to the placebo group. One participant in the PCV-10 group did not receive the vaccine and was excluded from subsequent analyses. The frequency of adverse events of grade 3 or higher during the first 4 weeks was similar in the vaccine and placebo groups (3% [90% CI 1–7] for the PCV-10 group, 2% [0–5] for the PPV-23 group, and 3% [1–8] for the placebo group). However, injection site and systemic grade 2 adverse reactions were reported more frequently during the first 4 weeks in the vaccine groups than in the placebo group (14% [9–20] for the PCV-10 group, 7% [4–12] for the PPV-23 group, and 3% [1–7] for the placebo group). The frequency of grade 3 or higher adverse effects was similar across maternal treatment groups (20% [14–27] for the PCV-10 group, 21% [14–28] for the PPV-23 group, and 20% [14–27] for the placebo group). Seroresponses against five or more serotypes were present in 74 (65%) of 114 women in the PCV-10 group, 72 (65%) of 110 women in the PPV-23 group, and none of the 113 women in the placebo group at 4 weeks post vaccination (p<0·0001 for PPV-23 group vs placebo and PCV-10 group vs placebo). Seroresponse differences of 20% or higher in vaccine compared with placebo recipients persisted up to 24 weeks post partum. At birth, 76 (67%) of 113 infants in the PCV-10 group, 62 (57%) of 109 infants in the PPV-23 group, and 19 (17%) of 115 infants in the placebo group had seroprotection against five or more serotypes (p<0·0001 for PPV-23 vs placebo and PCV-10 vs placebo). At 8 weeks, the outcome was met by 20 (19%) of 108 infants in the PCV-10 group, 24 (23%) of 104 infants in the PPV-23 group, and one (1%) of 109 infants in the placebo group (p<0·0001). Although a difference of 20% or higher compared with placebo was observed only in the infants who received PPV-23 at 8 weeks of life, the difference between the two vaccine groups was not appreciable. Interpretation: PCV-10 and PPV-23 were equally safe and immunogenic in pregnant women with HIV and conferred similar levels of seroprotection to their infants. In areas in which childhood PCV administration decreased the circulation of PCV serotypes, PPV-23 administration to pregnant women with HIV might be more advantageous than PCV by virtue of including a broader range of serotypes

    A framework for automated enrichment of functionally significant inverted repeats in whole genomes

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    <p>Abstract</p> <p>Background</p> <p>RNA transcripts from genomic sequences showing dyad symmetry typically adopt hairpin-like, cloverleaf, or similar structures that act as recognition sites for proteins. Such structures often are the precursors of non-coding RNA (ncRNA) sequences like microRNA (miRNA) and small-interfering RNA (siRNA) that have recently garnered more functional significance than in the past. Genomic DNA contains hundreds of thousands of such inverted repeats (IRs) with varying degrees of symmetry. But by collecting statistically significant information from a known set of ncRNA, we can sort these IRs into those that are likely to be functional.</p> <p>Results</p> <p>A novel method was developed to scan genomic DNA for partially symmetric inverted repeats and the resulting set was further refined to match miRNA precursors (pre-miRNA) with respect to their density of symmetry, statistical probability of the symmetry, length of stems in the predicted hairpin secondary structure, and the GC content of the stems. This method was applied on the <it>Arabidopsis thaliana</it> genome and validated against the set of 190 known Arabidopsis pre-miRNA in the miRBase database. A preliminary scan for IRs identified 186 of the known pre-miRNA but with 714700 pre-miRNA candidates. This large number of IRs was further refined to 483908 candidates with 183 pre-miRNA identified and further still to 165371 candidates with 171 pre-miRNA identified (i.e. with 90% of the known pre-miRNA retained).</p> <p>Conclusions</p> <p>165371 candidates for potentially functional miRNA is still too large a set to warrant wet lab analyses, such as northern blotting, on all of them. Hence additional filters are needed to further refine the number of candidates while still retaining most of the known miRNA. These include detection of promoters and terminators, homology analyses, location of candidate relative to coding regions, and better secondary structure prediction algorithms. The software developed is designed to easily accommodate such additional filters with a minimal experience in Perl.</p

    A Highly Conserved Poc1 Protein Characterized in Embryos of the Hydrozoan Clytia hemisphaerica: Localization and Functional Studies

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    Poc1 (Protein of Centriole 1) proteins are highly conserved WD40 domain-containing centriole components, well characterized in the alga Chlamydomonas, the ciliated protazoan Tetrahymena, the insect Drosophila and in vertebrate cells including Xenopus and zebrafish embryos. Functions and localizations related to the centriole and ciliary axoneme have been demonstrated for Poc1 in a range of species. The vertebrate Poc1 protein has also been reported to show an additional association with mitochondria, including enrichment in the specialized “germ plasm” region of Xenopus oocytes. We have identified and characterized a highly conserved Poc1 protein in the cnidarian Clytia hemisphaerica. Clytia Poc1 mRNA was found to be strongly expressed in eggs and early embryos, showing a punctate perinuclear localization in young oocytes. Fluorescence-tagged Poc1 proteins expressed in developing embryos showed strong localization to centrioles, including basal bodies. Anti-human Poc1 antibodies decorated mitochondria in Clytia, as reported in human cells, but failed to recognise endogenous or fluorescent-tagged Clytia Poc1. Injection of specific morpholino oligonucleotides into Clytia eggs prior to fertilization to repress Poc1 mRNA translation interfered with cell division from the blastula stage, likely corresponding to when neosynthesis normally takes over from maternally supplied protein. Cell cycle lengthening and arrest were observed, phenotypes consistent with an impaired centriolar biogenesis or function. The specificity of the defects could be demonstrated by injection of synthetic Poc1 mRNA, which restored normal development. We conclude that in Clytia embryos, Poc1 has an essentially centriolar localization and function
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