IMPORTANCE: Fetal safety of magnetic resonance imaging (MRI) during the first trimester of pregnancy or with gadolinium enhancement at any time of pregnancy is unknown. OBJECTIVE: To evaluate the ...long-term safety after exposure to MRI in the first trimester of pregnancy or to gadolinium at any time during pregnancy. DESIGN, SETTING, AND PARTICIPANTS: Universal health care databases in the province of Ontario, Canada, were used to identify all births of more than 20 weeks, from 2003-2015. EXPOSURES: Magnetic resonance imaging exposure in the first trimester of pregnancy, or gadolinium MRI exposure at any time in pregnancy. MAIN OUTCOMES AND MEASURES: For first-trimester MRI exposure, the risk of stillbirth or neonatal death within 28 days of birth and any congenital anomaly, neoplasm, and hearing or vision loss was evaluated from birth to age 4 years. For gadolinium-enhanced MRI in pregnancy, connective tissue or skin disease resembling nephrogenic systemic fibrosis (NSF-like) and a broader set of rheumatological, inflammatory, or infiltrative skin conditions from birth were identified. RESULTS: Of 1 424 105 deliveries (48% girls; mean gestational age, 39 weeks), the overall rate of MRI was 3.97 per 1000 pregnancies. Comparing first-trimester MRI (n = 1737) to no MRI (n = 1 418 451), there were 19 stillbirths or deaths vs 9844 in the unexposed cohort (adjusted relative risk RR, 1.68; 95% CI, 0.97 to 2.90) for an adjusted risk difference of 4.7 per 1000 person-years (95% CI, −1.6 to 11.0). The risk was also not significantly higher for congenital anomalies, neoplasm, or vision or hearing loss. Comparing gadolinium MRI (n = 397) with no MRI (n = 1 418 451), the hazard ratio for NSF-like outcomes was not statistically significant. The broader outcome of any rheumatological, inflammatory, or infiltrative skin condition occurred in 123 vs 384 180 births (adjusted HR, 1.36; 95% CI, 1.09 to 1.69) for an adjusted risk difference of 45.3 per 1000 person-years (95% CI, 11.3 to 86.8). Stillbirths and neonatal deaths occurred among 7 MRI-exposed vs 9844 unexposed pregnancies (adjusted RR, 3.70; 95% CI, 1.55 to 8.85) for an adjusted risk difference of 47.5 per 1000 pregnancies (95% CI, 9.7 to 138.2). CONCLUSIONS AND RELEVANCE: Exposure to MRI during the first trimester of pregnancy compared with nonexposure was not associated with increased risk of harm to the fetus or in early childhood. Gadolinium MRI at any time during pregnancy was associated with an increased risk of a broad set of rheumatological, inflammatory, or infiltrative skin conditions and for stillbirth or neonatal death. The study may not have been able to detect rare adverse outcomes.
Climate Change and Food Systems Vermeulen, Sonja J; Campbell, Bruce M; Ingram, John S.I
Annual review of environment and resources,
11/2012, Letnik:
37, Številka:
1
Journal Article
Recenzirano
Food systems contribute 19%-29% of global anthropogenic greenhouse gas (GHG) emissions, releasing 9,800-16,900 megatonnes of carbon dioxide equivalent (MtCO
2
e) in 2008. Agricultural production, ...including indirect emissions associated with land-cover change, contributes 80%-86% of total food system emissions, with significant regional variation. The impacts of global climate change on food systems are expected to be widespread, complex, geographically and temporally variable, and profoundly influenced by socioeconomic conditions. Historical statistical studies and integrated assessment models provide evidence that climate change will affect agricultural yields and earnings, food prices, reliability of delivery, food quality, and, notably, food safety. Low-income producers and consumers of food will be more vulnerable to climate change owing to their comparatively limited ability to invest in adaptive institutions and technologies under increasing climatic risks. Some synergies among food security, adaptation, and mitigation are feasible. But promising interventions, such as agricultural intensification or reductions in waste, will require careful management to distribute costs and benefits effectively.
The natural antibiotic teixobactin kills pathogenic bacteria without detectable resistance. The difficult synthesis and unfavourable solubility of teixobactin require modifications, yet insufficient ...knowledge on its binding mode impedes the hunt for superior analogues. Thus far, teixobactins are assumed to kill bacteria by binding to cognate cell wall precursors (Lipid II and III). Here we present the binding mode of teixobactins in cellular membranes using solid-state NMR, microscopy, and affinity assays. We solve the structure of the complex formed by an improved teixobactin-analogue and Lipid II and reveal how teixobactins recognize a broad spectrum of targets. Unexpectedly, we find that teixobactins only weakly bind to Lipid II in cellular membranes, implying the direct interaction with cell wall precursors is not the sole killing mechanism. Our data suggest an additional mechanism affords the excellent activity of teixobactins, which can block the cell wall biosynthesis by capturing precursors in massive clusters on membranes.
Food security is high on the global policy agenda. Demand for food is increasing as populations grow and gain wealth to purchase more varied and resource-intensive diets. There is increased ...competition for land, water, energy, and other inputs into food production. Climate change poses challenges to agriculture, particularly in developing countries (1), and many current farming practices damage the environment and are a major source of greenhouse gases (GHG). In an increasingly globalized world, food insecurity in one region can have widespread political and economic ramifications (2).
Plant communities with traits that would maximize community performance can be invaded by plants that invest extra in acquiring resources at the expense of others, lowering the overall community ...performance, a so-called tragedy of the commons (TOC). By contrast, maximum community performance is usually the objective in agriculture. We first give an overview of the occurrence of TOCs in plants, and explore the extent to which past crop breeding has led to trait values that go against an unwanted TOC. We then show how linking evolutionary game theory (EGT) with mechanistic knowledge of the physiological processes that drive trait expression and the ecological aspects of biotic interactions in agro-ecosystems might contribute to increasing crop yields and resource-use efficiency.
Current increases in crop production are falling below the 2% annual rise needed to maintain global food security, while restrictions on the use of synthetic fertilizers and pesticides are increasing. This calls for new more ecology-based directions in crop breeding and management.
Optimal plant communities with maximum growth or seed production are often not stable against invasion by individuals that invest more in resource harvesting. These effects have been framed as TOCs and conflict with the need in agriculture for increased yields and ecosystem service provisioning.
Recently there is increased interest in assessing how these TOCs arise and how this knowledge in turn may give directions for crop breeding and management. Linking evolutionary game theory (EGT) – the key mathematical tool to analyze natural selection in situations where organisms interact – to our increased understanding of the physiological regulation of trait expression and ecological interactions in agro-ecosystems provides a framework through which this can be achieved.
Fatigue during walking is a common complaint in cerebral palsy (CP). The primary purpose of this study is to investigate muscle fatigue from surface electromyography (sEMG) measurements after a ...treadmill-based fatigue protocol with increasing incline and speed in children with CP with drop foot. The secondary purpose is to investigate whether changes in sagittal kinematics of hip, knee and ankle occur after fatigue. Eighteen subjects with unilateral spastic CP performed the protocol while wearing their ankle-foot orthosis and scored their fatigue on the OMNI scale of perceived exertion. The median frequency (MF) and root mean square (RMS) were used as sEMG measures for fatigue and linear mixed effects model were applied. The MF was significantly decreased in fatigued condition, especially in the affected leg and in the tibialis anterior and peroneus longus muscle. The RMS did not change significantly in fatigued condition, while the OMNI fatigue score indicated patients felt really fatigued. No changes in sagittal kinematics of hip, knee and ankle were found using statistical non-parametric mapping. In conclusion, the current fatigue protocol seems promising in inducing fatigue in a population with CP with drop foot and it could be used to expand knowledge on muscle fatigue during walking in CP.
The prototype demonstrated here is the first fully integrated sample-to-result diagnostic platform for performing nucleic acid amplification tests that requires no permanent instrument or manual ...sample processing. The multiplexable autonomous disposable nucleic acid amplification test (MAD NAAT) is based on two-dimensional paper networks, which enable sensitive chemical detection normally reserved for laboratories to be carried out anywhere by untrained users. All reagents are stored dry in the disposable test device and are rehydrated by stored buffer. The paper network is physically multiplexed to allow independent isothermal amplification of multiple targets; each amplification reaction is also chemically multiplexed with an internal amplification control. The total test time is less than one hour. The MAD NAAT prototype was used to characterize a set of human nasal swab specimens pre-screened for methicillin-resistant Staphylococcus aureus (MRSA) bacteria. With qPCR as the quantitative reference method, the lowest input copy number in the range where the MAD NAAT prototype consistently detected MRSA in these specimens was ∼5 × 10(3) genomic copies (∼600 genomic copies per biplexed amplification reaction).
Abstract
Antibiotics that use novel mechanisms are needed to combat antimicrobial resistance
1–3
. Teixobactin
4
represents a new class of antibiotics with a unique chemical scaffold and lack of ...detectable resistance. Teixobactin targets lipid II, a precursor of peptidoglycan
5
. Here we unravel the mechanism of teixobactin at the atomic level using a combination of solid-state NMR, microscopy, in vivo assays and molecular dynamics simulations. The unique enduracididine C-terminal headgroup of teixobactin specifically binds to the pyrophosphate-sugar moiety of lipid II, whereas the N terminus coordinates the pyrophosphate of another lipid II molecule. This configuration favours the formation of a β-sheet of teixobactins bound to the target, creating a supramolecular fibrillar structure. Specific binding to the conserved pyrophosphate-sugar moiety accounts for the lack of resistance to teixobactin
4
. The supramolecular structure compromises membrane integrity. Atomic force microscopy and molecular dynamics simulations show that the supramolecular structure displaces phospholipids, thinning the membrane. The long hydrophobic tails of lipid II concentrated within the supramolecular structure apparently contribute to membrane disruption. Teixobactin hijacks lipid II to help destroy the membrane. Known membrane-acting antibiotics also damage human cells, producing undesirable side effects. Teixobactin damages only membranes that contain lipid II, which is absent in eukaryotes, elegantly resolving the toxicity problem. The two-pronged action against cell wall synthesis and cytoplasmic membrane produces a highly effective compound targeting the bacterial cell envelope. Structural knowledge of the mechanism of teixobactin will enable the rational design of improved drug candidates.
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