COVID-19 vaccines have proven highly effective among individuals without a previous SARS-CoV-2 infection, but their effectiveness in preventing symptomatic infection and severe outcomes among ...individuals with previous infection is less clear. We aimed to estimate the effectiveness of four COVID-19 vaccines against symptomatic infection, hospitalisation, and death for individuals with laboratory-confirmed previous SARS-CoV-2 infection.
Using national COVID-19 notification, hospitalisation, and vaccination datasets from Brazil, we did a test-negative, case-control study to assess the effectiveness of four vaccines (CoronaVac Sinovac, ChAdOx1 nCoV-19 AstraZeneca, Ad26.COV2.S Janssen, and BNT162b2 Pfizer-BioNtech) for individuals with laboratory-confirmed previous SARS-CoV-2 infection. We matched cases with RT-PCR positive, symptomatic COVID-19 with up to ten controls with negative RT-PCR tests who presented with symptomatic illnesses, restricting both groups to tests done at least 90 days after an initial infection. We used multivariable conditional logistic regression to compare the odds of test positivity and the odds of hospitalisation or death due to COVID-19, according to vaccination status and time since first or second dose of vaccines.
Between Feb 24, 2020, and Nov 11, 2021, we identified 213 457 individuals who had a subsequent, symptomatic illness with RT-PCR testing done at least 90 days after their initial SARS-CoV-2 infection and after the vaccination programme started. Among these, 30 910 (14·5%) had a positive RT-PCR test consistent with reinfection, and we matched 22 566 of these cases with 145 055 negative RT-PCR tests from 68 426 individuals as controls. Among individuals with previous SARS-CoV-2 infection, vaccine effectiveness against symptomatic infection 14 or more days from vaccine series completion was 39·4% (95% CI 36·1–42·6) for CoronaVac, 56·0% (51·4–60·2) for ChAdOx1 nCoV-19, 44·0% (31·5–54·2) for Ad26.COV2.S, and 64·8% (54·9–72·4) for BNT162b2. For the two-dose vaccine series (CoronaVac, ChAdOx1 nCoV-19, and BNT162b2), effectiveness against symptomatic infection was significantly greater after the second dose than after the first dose. Effectiveness against hospitalisation or death 14 or more days from vaccine series completion was 81·3% (75·3–85·8) for CoronaVac, 89·9% (83·5–93·8) for ChAdOx1 nCoV-19, 57·7% (−2·6 to 82·5) for Ad26.COV2.S, and 89·7% (54·3–97·7) for BNT162b2.
All four vaccines conferred additional protection against symptomatic infections and severe outcomes among individuals with previous SARS-CoV-2 infection. The provision of a full vaccine series to individuals after recovery from COVID-19 might reduce morbidity and mortality.
Brazilian National Research Council, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Oswaldo Cruz Foundation, JBS, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Generalitat de Catalunya.
Abstract Background The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more ...complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism. Scope of review In this review, we discuss the diverse biological functions of ghrelin, the regulation of its secretion, and address questions that still remain 15 years after its discovery. Major conclusions In recent years, ghrelin has been found to have a plethora of central and peripheral actions in distinct areas including learning and memory, gut motility and gastric acid secretion, sleep/wake rhythm, reward seeking behavior, taste sensation and glucose metabolism.
We consider here first the nature of nutrient transport through estuaries and in particular the capacity of estuaries to modify that flux. We then focus particularly on the Wash system in the UK as ...an example of a particular type of “small estuary”, and also consider some tropical estuarine systems in Malaysia. We present nutrient budgets for the Wash system now and create estimates of these budgets 3000 years ago. These show that currently the system is a small sink for fluvial nitrate (∼30% removal) largely due to denitrification and dissolved inorganic phosphorus (∼24%) by burial. 3000 years ago, prior to large scale human intervention to reclaim wetlands for agriculture, the Wash system was much bigger and operated as a sink for all terrestrial nitrogen (albeit with much lower inputs) and also a sink for nitrate from the North Sea, predominantly via organic nitrogen burial. A similar change with time is evident in the phosphorus flux. We suggest that this change in function of this estuarine system has been replicated in many other estuarine systems. Given the key role of benthic processes of burial and denitrification we go on to suggest that the classification of estuaries in terms of area and river flow may offer a route to a typology of estuarine nutrient retention efficiency.
•Nutrient retention in estuaries depends on the “geography” of an estuary.•This geography is being modified greatly by human activity.•Changes in geography and inputs contribute to changing fluxes to coastal waters.
Viruses have evolved diverse strategies to evade the host innate immune response and promote infection. The retinoic acid-inducible gene I (RIG-I)-like receptors RIG-I and MDA5 are antiviral factors ...that sense viral RNA and trigger downstream signal via mitochondrial antiviral-signaling protein (MAVS) to activate type I interferon expression. 14-3-3ε is a key component of the RIG-I translocon complex that interacts with MAVS at the mitochondrial membrane; however, the exact role of 14-3-3ε in this pathway is not well understood. In this study, we demonstrate that 14-3-3ε is a direct substrate of both the poliovirus and coxsackievirus B3 (CVB3) 3C proteases (3C
) and that it is cleaved at Q236↓G237, resulting in the generation of N- and C-terminal fragments of 27.0 and 2.1 kDa, respectively. While the exogenous expression of wild-type 14-3-3ε enhances
mRNA production during poly(I:C) stimulation, expression of the truncated N-terminal fragment does not. The N-terminal 14-3-3ε fragment does not interact with RIG-I in co-immunoprecipitation assays, nor can it facilitate RIG-I translocation to the mitochondria. Probing the intrinsically disordered C-terminal region identifies key residues responsible for the interaction between 14-3-3ε and RIG-I. Finally, overexpression of the N-terminal fragment promotes CVB3 infection in mammalian cells. The strategic enterovirus 3C
-mediated cleavage of 14-3-3ε antagonizes RIG-I signaling by disrupting critical interactions within the RIG-I translocon complex, thus contributing to evasion of the host antiviral response. IMPORTANCE Host antiviral factors work to sense virus infection through various mechanisms, including a complex signaling pathway known as the retinoic acid-inducible gene I (RIG-I)-like receptor pathway. This pathway drives the production of antiviral molecules known as interferons, which are necessary to establish an antiviral state in the cellular environment. Key to this antiviral signaling pathway is the small chaperone protein 14-3-3ε, which facilitates the delivery of a viral sensor protein, RIG-I, to the mitochondria. In this study, we show that the enteroviral 3C protease cleaves 14-3-3ε during infection, rendering it incapable of facilitating this antiviral response. We also find that the resulting N-terminal cleavage fragment dampens RIG-I signaling and promotes virus infection. Our findings reveal a novel viral strategy that restricts the antiviral host response and provides insights into the mechanisms underlying 14-3-3ε function in RIG-I antiviral signaling.
Recent results from the MAVEN Langmuir Probe and Waves instrument suggest higher than predicted electron temperatures (Te) in Mars' dayside ionosphere above ~180 km in altitude. Correspondingly, ...measurements from Neutral Gas and Ion Mass Spectrometer indicate significant abundances of O2+ up to ~500 km in altitude, suggesting that O2+ may be a principal ion loss mechanism of oxygen. In this article, we investigate the effects of the higher Te (which results from electron heating) and ion heating on ion outflow and loss. Numerical solutions show that plasma processes including ion heating and higher Te may greatly increase O2+ loss at Mars. In particular, enhanced Te in Mars' ionosphere just above the exobase creates a substantial ambipolar electric field with a potential (eΦ) of several kBTe, which draws ions out of the region allowing for enhanced escape. With active solar wind, electron, and ion heating, direct O2+ loss could match or exceed loss via dissociative recombination of O2+. These results suggest that direct loss of O2+ may have played a significant role in the loss of oxygen at Mars over time.
Key Points
O2+ outflow at Mars is greatly enhanced by ambipolar electric field
Enhanced electron temperatures result in a strong ambipolar electric field
In the past, direct loss of O2+ could have exceeded that of associative recombination
A two-dose regimen of the Oxford-AstraZeneca (ChAdOx1) Covid-19 vaccine with an inter-dose interval of three months has been implemented in many countries with restricted vaccine supply. However, ...there is limited evidence for the effectiveness of ChAdOx1 by dose in elderly populations in countries with high prevalence of the Gamma variant of SARS-CoV-2. Here, we estimate ChAdOx1 effectiveness by dose against the primary endpoint of RT-PCR-confirmed Covid-19, and secondary endpoints of Covid-19 hospitalization and Covid-19-related death, in adults aged ≥60 years during an epidemic with high Gamma variant prevalence in São Paulo state, Brazil using a matched, test-negative case-control study. Starting 28 days after the first dose, effectiveness of a single dose of ChAdOx1 is 33.4% (95% CI, 26.4-39.7) against Covid-19, 55.1% (95% CI, 46.6-62.2) against hospitalization, and 61.8% (95% CI, 48.9-71.4) against death. Starting 14 days after the second dose, effectiveness of the two-dose schedule is 77.9% (95% CI, 69.2-84.2) against Covid-19, 87.6% (95% CI, 78.2-92.9) against hospitalization, and 93.6% (95% CI, 81.9-97.7) against death. Completion of the ChAdOx1 vaccine schedule affords significantly increased protection over a single dose against mild and severe Covid-19 outcomes in elderly individuals during widespread Gamma variant circulation.
Vertically aligned carbon nanofiber (CNF) arrays, particularly when coated with a polypyrrole film, show well‐defined electrical properties with extremely low impedance. The polymer film also serves ...as a biomaterial (with great freedom of chemical and biological modification) for cell/tissue engineering to create an intimate subcellular electrical–neural interface, which is desirable for implantable biomedical devices. The Figure shows a single PC12 neural cell (green) spanning collagen‐coated CNF microbundles.
Environmental surveillance, using detection of Salmonella Typhi DNA, has emerged as a potentially useful tool to identify typhoid-endemic settings; however, it is relatively costly and requires ...molecular diagnostic capacity. We sought to determine whether S. Typhi bacteriophages are abundant in water sources in a typhoid-endemic setting, using low-cost assays.
We collected drinking and surface water samples from urban, peri-urban and rural areas in 4 regions of Nepal. We performed a double agar overlay with S. Typhi to assess the presence of bacteriophages. We isolated and tested phages against multiple strains to assess their host range. We performed whole genome sequencing of isolated phages, and generated phylogenies using conserved genes.
S. Typhi-specific bacteriophages were detected in 54.9% (198/361) of river and 6.3% (1/16) drinking water samples from the Kathmandu Valley and Kavrepalanchok. Water samples collected within or downstream of population-dense areas were more likely to be positive (72.6%, 193/266) than those collected upstream from population centers (5.3%, 5/95) (p=0.005). In urban Biratnagar and rural Dolakha, where typhoid incidence is low, only 6.7% (1/15, Biratnagar) and 0% (0/16, Dolakha) river water samples contained phages. All S. Typhi phages were unable to infect other Salmonella and non-Salmonella strains, nor a Vi-knockout S. Typhi strain. Representative strains from S. Typhi lineages were variably susceptible to the isolated phages. Phylogenetic analysis showed that S. Typhi phages belonged to the class Caudoviricetes and clustered in three distinct groups.
S. Typhi bacteriophages were highly abundant in surface waters of typhoid-endemic communities but rarely detected in low typhoid burden communities. Bacteriophages recovered were specific for S. Typhi and required Vi polysaccharide for infection. Screening small volumes of water with simple, low-cost (~$2) plaque assays enables detection of S. Typhi phages and should be further evaluated as a scalable tool for typhoid environmental surveillance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Postauthorization observational studies play a key role in understanding COVID-19 vaccine effectiveness following the demonstration of efficacy in clinical trials. Although bias due to confounding, ...selection bias, and misclassification can be mitigated through careful study design, unmeasured confounding is likely to remain in these observational studies. Phase III trials of COVID-19 vaccines have shown that protection from vaccination does not occur immediately, meaning that COVID-19 risk should be similar in recently vaccinated and unvaccinated individuals, in the absence of confounding or other bias. Several studies have used the estimated effectiveness among recently vaccinated individuals as a negative control exposure to detect bias in vaccine effectiveness estimates. In this paper, we introduce a theoretical framework to describe the interpretation of such a bias indicator in test-negative studies, and outline strong assumptions that would allow vaccine effectiveness among recently vaccinated individuals to serve as a negative control exposure.
We demonstrate that land reclamation in estuaries is resulting in very large-scale loss of intertidal area and disconnection of stored sediment with the water column. This process is not just causing ...loss of estuarine ecosystem services, it is also having a major deleterious impact on the ability of estuaries to retain nutrients and trace metals. The global scale of loss of estuarine wetlands and subtidal sediments has reached the point where the impact of this loss of estuarine retention is likely to be affecting coastal seas worldwide and possibly global element cycles.
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