Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory ...syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown.
In a retrospective study based on a U.S. national registry, we determined the anti-SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19. The primary outcome was death within 30 days after plasma transfusion. Patients who were enrolled through July 4, 2020, and for whom data on anti-SARS-CoV-2 antibody levels in plasma transfusions and on 30-day mortality were available were included in the analysis.
Of the 3082 patients included in this analysis, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group. The association of anti-SARS-CoV-2 antibody levels with the risk of death from Covid-19 was moderated by mechanical ventilation status. A lower risk of death within 30 days in the high-titer group than in the low-titer group was observed among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% confidence interval CI, 0.48 to 0.91), and no effect on the risk of death was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78 to 1.32).
Among patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti-SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT04338360.).
Greater rates of genetic gain can be achieved by selecting animals born to younger parents. However, little is known about the lifetime performance of dual purpose ewes (Ovis aries) that are born to ...primiparous ewe lambs (8 to 9 months old at breeding). This experiment investigated the effect of being born from either a ewe lamb or mixed age dam as either a single or twin on the lifetime performance of ewe progeny. Lifetime performance was measured in terms of the life time live weights of the ewes, the weight and number of lambs born and weaned, the efficiency of production (kilograms of lamb weaned / predicted pasture intake (kgDM) of the ewes), and ewe survival. The study followed the lifetime production of 17 single and 41 twin female lambs born to mature ewes (M1 and M2, respectively), and 28 single and 29 twin lambs born to ewe lambs (L1 and L2, respectively). Over their lifetime L2 ewes were lighter (P<0.05) but had similar body condition scores to the other three ewe groups. There was no difference in average progeny weaning weight or total progeny litter weaning weights between groups. The M1 ewes had the greatest longevity (P<0.05) of the four groups. Even though L2 ewes were lighter than the other three groups, this was insufficient to increase their lifetime efficiency of production (kg lamb weaned/predicted pasture consumption), relative to the other groups. These results suggest farmers could select replacements born to ewe lambs without sacrificing animal production.
Exercise therapy - the public health message Blair, S. N.; Sallis, R. E.; Hutber, A. ...
Scandinavian journal of medicine & science in sports,
August 2012, Letnik:
22, Številka:
4
Journal Article
Recenzirano
Non‐communicable chronic diseases (NCDs), such as cardiovascular disease, diabetes, and cancer, are currently responsible for 65% of all deaths worldwide and are projected to cause over 75% of all ...deaths by 2030. A substantial accumulation of epidemiological and experimental evidence has established a causal relationship between NCDs and well‐known yet preventable risk factors (e.g., physical inactivity and obesity). Given that physical activity has both direct and indirect effects on the mortality and morbidity of NCDs via other risk factors (e.g., obesity, diabetes, and hypertension), it is now undeniable that sedentary lifestyles are one of the most significant public health problems of the 21st century.
In 2007, the American College of Sports Medicine (ACSM) and American Medical Association (AMA) launched the Exercise is Medicine® (EIM) initiative in recognition of the fundamental importance of physical activity to health and well‐being. EIM is on the forefront of a global movement to reduce sedentary lifestyles, foster implementation of exercise counseling into clinical practice, and disseminate exercise therapy on a global scale. If the devastating human losses and financial burden of inactivity‐induced chronic disease are to be ameliorated, the wide‐ranging cost‐effective health benefits and financial feasibility of physical activity interventions must be appreciated and promoted.
High-resolution microscopy of deep tissue with large field-of-view (FOV) is critical for elucidating organization of cellular structures in plant biology. Microscopy with an implanted probe offers an ...effective solution. However, there exists a fundamental trade-off between the FOV and probe diameter arising from aberrations inherent in conventional imaging optics (typically, FOV < 30% of diameter). Here, we demonstrate the use of microfabricated non-imaging probes (optrodes) that when combined with a trained machine-learning algorithm is able to achieve FOV of 1x to 5x the probe diameter. Further increase in FOV is achieved by using multiple optrodes in parallel. With a 1 × 2 optrode array, we demonstrate imaging of fluorescent beads (including 30 FPS video), stained plant stem sections and stained living stems. Our demonstration lays the foundation for fast, high-resolution microscopy with large FOV in deep tissue via microfabricated non-imaging probes and advanced machine learning.
Tumor inflammation promotes angiogenesis, immunosuppression, and tumor growth, but the mechanisms controlling inflammatory cell recruitment to tumors are not well understood. We found that a range of ...chemoattractants activating G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and Toll-like/IL-1 receptors (TLR/IL1Rs) unexpectedly initiate tumor inflammation by activating the PI3-kinase isoform p110γ in Gr1+CD11b+ myeloid cells. Whereas GPCRs activate p110γ in a Ras/p101-dependent manner, RTKs and TLR/IL1Rs directly activate p110γ in a Ras/p87-dependent manner. Once activated, p110γ promotes inside-out activation of a single integrin, α4β1, causing myeloid cell invasion into tumors. Pharmacological or genetic blockade of p110γ suppressed inflammation, growth, and metastasis of implanted and spontaneous tumors, revealing an important therapeutic target in oncology.
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► Tumor inflammation depends on myeloid cell p110γ and integrin α4β1 ► RTKs, TLR/ILRs, and GPCRs directly activate p110γ to promote tumor inflammation ► RTKs and TLR/ILRs activate p110γ via p87 and Ras independently of GPCRs ► Inhibitors of p110γ block tumor inflammation, growth, and progression
A 28-day battery cage study was conducted to test the efficacy of tannin-free grain sorghum varieties fed to Cobb 500 male broiler chickens (n = 512) and challenged with Eimeria maxima (EM) and ...Clostridium perfringens (CP). Birds were fed 1 of 8 treatments (corn, red/bronze, white/tan, or U.S. No. 2 sorghum) and were grouped by challenge method (challenged with EM/CP or unchallenged). On d 14, birds in the challenge group were orally inoculated with ∼5,000 oocysts of EM, and on d 19, 20, and 21, birds were given a broth culture of CP with ∼108 CFU/mL once daily. On d 21, three birds were scored for the degree/presence of necrotic enteritis (NE) lesions. Birds and feed were group weighed (d 0, 14, 21, and 28) to calculate average feed intake (FI), body weight gain (BWG), and adjusted feed conversion ratio (AdjFCR). Intestinal integrity was assessed through histological analysis of intestinal tissues, and change in transcriptome was determined using mRNA-sequencing on intestinal mucosa. Relative concentrations of secondary metabolites in grain sorghum were determined by LC-MS/MS analysis. Data were analyzed as a 2-way ANOVA with factors of treatment, challenge and their interaction. Regardless of challenge from 14 to 21 d, birds on the corn, white/tan, and U.S. No. 2 treatments were more efficient than those fed red/bronze treatment (P = 0.0026). From 14 to 28 d, BWG was significantly higher for the white/tan treatment (P = 0.024) compared to the red/bronze treatment. At 21 d, a significant interaction was observed for lesion score (P = 0.0001) in which, challenged birds fed red/bronze and white/tan treatments had reduced intestinal lesions compared to U.S. No. 2 and corn treatments. No differences among treatments were observed in jejunum morphology, but differential expression analysis showed an upregulation in defense response to bacteria and biotic stress in the challenged red/bronze treatment compared to the challenged corn. This study demonstrated improved gut health and minimal impact on growth and efficiency of broilers fed select grain sorghum varieties when challenged with EM/CP.
A fundamental goal of the Earth Science community is to understand how perturbations on Earth's surface are preserved in the stratigraphic record. Recent Source to Sink (S2S) studies of the Waipaoa ...Sedimentary System (WSS), New Zealand, are synthesized herein to provide a holistic perspective of the processes that generate, transport and preserve sedimentary strata and organic carbon on the Waipaoa margin in the late Quaternary. Rapid uplift associated with subduction processes and weak sedimentary units have conspired to generate rapid rates of incision and erosion in the Waipaoa catchment since the Last Glacial Maximum (LGM). We show that although much of the sediment exported offshore during this time interval originated from valley excavation, a substantial portion emanated from hillslopes, mostly through deep-seated landslide and earthflow processes that were vigorous during periods of rapid fluvial incision just prior to the Pleistocene–Holocene transition. Lacustrine sediments deposited in naturally-dammed 7-ky-old Lake Tutira provide a record of Holocene environmental controls on upper catchment sedimentation in the WSS, with 1400 storms identified. Storm frequency is modulated by the waxing and waning of atmospheric teleconnections between the tropics and Antarctica. Furthermore, clear long-term changes in sediment yield are evident from the Lake Tutira record following human settlement as conversion to pasture is accompanied by a 3-fold increase in the long-term lake sediment accumulation rate.
Whereas there is ample evidence that Waipaoa River flood deposits are routinely deposited offshore in the sheltered confines of Poverty Bay, over the longer term, waves and currents subsequently resuspend and transport these deposits both landward (sandy fraction) and seaward (finer fraction). Thus, the timing of sediment supply to areas of net sediment accumulation is more often driven by wave events that are not associated with river flooding. Therefore, we conclude that asynchronicity of river-sediment delivery and of wave resuspension in most instances precludes the direct preservation of flood events in the stratigraphic record of the Waipaoa Shelf. Over the longer term, the sediment package preserved on the shelf and slope since the LGM can be explained in large measure by sequence-stratigraphic models forced by varying sea level and ongoing tectonic deformation of the margin. As sea level rose, sediment supply to the slope was reduced by about a factor of 5 due to shelf trapping. Despite this reduction, turbidites are found at similar frequency throughout the LGM–Present, as the dominant trigger appears to be subduction earthquakes, with large ones having a return interval of about 200±100years. Sediment-budget exercises that consider both modern (river discharge versus centennial accumulation rates) and post-LGM (terrestrial production versus offshore isopachs) mass balances indicate that about half of the total sediment production from the Waipaoa escapes the study area. Moreover, a coupled sediment transport-hydrodynamic model and observations of textural trends on the shelf indicate that a large fraction of the sediment is carried outside the study area along the shelf to the northeast by the river plume or by combined current/wave activity. Therefore, we conclude that the WSS is an open system with sediment escape from the present day through the LGM.
The organic matter associated with sediment as it moves from upland source to marine sink is a product of particle history, and provides a record of materials that have cycled over timescales of days to millions of years. The ubiquity of fossil Organic Carbon (OC) in both the terrestrial and marine realms of the Waipaoa attests both to the chronic nature of its source, crumbling mudstones further destabilized by land use, and its biogeochemical recalcitrance. Modern OC persists by virtue of its continual production along the S2S transit, and is buried and preserved within the adjacent marine depocenters. The Waipaoa contrasts with dispersal systems on wide, energetic shelves (e.g., the Amazon and Fly Rivers) where sediment is extensively refluxed in oxygenated overlying water resulting in the biogeochemical incineration of particulate OC. The Waipaoa, like other small mountainous rivers on active margins, exhibits a high riverine OC preservation efficiency (>50%) in its marine depocenters because of the relatively rapid, event-driven accumulation of sediment.
Objective: This study was performed to determine the apparent metabolizable energy (AMEn) content of tannin-free red/bronze, white/tan and U.S. No. 2 varieties of grain sorghum for feeding Japanese ...quail and validate their nutrient profile by evaluating effects on performance and carcass traits with full-substitution of corn.Methods: Experiment 1 determined the AMEn content of red/bronze, white/tan, and U.S. No. 2 grain sorghum varieties fed to mixed-sex Japanese quail (Coturnix japonica) (n = 314) at 3 and 6-weeks of age. Analyses were based on a 2×4 factorial treatment design with age and grain types defining the treatments, and a randomized complete block experiment design with cage and trials defining the block. AMEn values were validated by evaluating the performance and carcass traits of Japanese quail (n = 644) from 1 to 40 days of age in Experiment 2 with birds were fed 1 of 4 complete diets. Statistical analyses were conducted on performance data and select individual carcass trait measurements.Results: Determined AMEn values at 3-weeks of age were 3,524±122.03 (red/bronze), 3,252±122.03 (white/tan), and 3,039±123.44 (U.S. No. 2) kcal/kg. At 6-weeks of age, determined AMEn were 3,373±297.35 (red/bronze), 3,279±297.35 (white/tan), and 2,966±298.64 (U.S. No. 2) kcal/kg. Carcass traits showed live body weight (p = 0.0409) and hot carcass weight (p = 0.0234) were greatest in U.S. No. 2; however, carcass yield (p<0.0001) was lowest. No significant differences were observed among treatments for feed intake, feed conversion ratio, breast weight and breast yield (p>0.05).Conclusion: These studies demonstrated that tannin-free grain sorghum varieties may be a potential alternative to corn in quail diets while maintaining growth performance and carcass parameters.
Abstract Activation of the cannabinoid type 1 (CB1) receptor, a major G-protein-coupled receptor in brain, acts to regulate neuronal excitability and has been shown to mediate the anticonvulsant ...effects of cannabinoids in several animal models of seizure, including the rat pilocarpine model of acquired epilepsy. However, the long-term effects of status epilepticus on the expression and function of the CB1 receptor have not been described. Therefore, this study was initiated to evaluate the effect of status epilepticus on CB1 receptor expression, binding, and G-protein activation in the rat pilocarpine model of acquired epilepsy. Using immunohistochemistry, we demonstrated that status epilepticus causes a unique “redistribution” of hippocampal CB1 receptors, consisting of specific decreases in CB1 immunoreactivity in the dense pyramidal cell layer neuropil and dentate gyrus inner molecular layer, and increases in staining in the CA1-3 strata oriens and radiatum. In addition, this study demonstrates that the redistribution of CB1 receptor expression results in corresponding functional changes in CB1 receptor binding and G-protein activation using 3 H R (+)-2,3-dihydro-5-methyl-3-(morpholinyl)methylpyrrolo1,2,3- de -1,4-benzoxazin-yl(1-napthalen-yl)methanone mesylate (WIN55,212-2) and agonist-stimulated 35 SGTPγS autoradiography, respectively. The redistribution of CB1 receptor-mediated 35 SGTPγS binding was 1) attributed to an altered maximal effect (Emax ) of WIN55,212-2 to stimulate 35 SGTPγS binding, 2) reversed by the CB1 receptor antagonist N -(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1 H -pyrazole-3-carboxamide hydrochloride (SR141716A), 3) confirmed by the use of other CB1 receptor agonists, and 4) not reproduced in other G-protein-coupled receptor systems examined. These results demonstrate that status epilepticus causes a unique and selective reorganization of the CB1 receptor system that persists as a permanent hippocampal neuronal plasticity change associated with the development of acquired epilepsy.
The 2,272,351-base pair genome of Neisseria meningitidis strain MC58 (serogroup B), a causative agent of meningitis and septicemia, contains 2158 predicted coding regions, 1158 (53.7%) of which were ...assigned a biological role. Three major islands of horizontal DNA transfer were identified; two of these contain genes encoding proteins involved in pathogenicity, and the third island contains coding sequences only for hypothetical proteins. Insights into the commensal and virulence behavior of N. meningitidis can be gleaned from the genome, in which sequences for structural proteins of the pilus are clustered and several coding regions unique to serogroup B capsular polysaccharide synthesis can be identified. Finally, N. meningitidis contains more genes that undergo phase variation than any pathogen studied to date, a mechanism that controls their expression and contributes to the evasion of the host immune system.
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