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The present paper reviews the evidence as to whether patients on lipid-lowering drugs should restrict dietary SFA intake. Premature mortality from atherosclerotic CVD has fallen dramatically in many high-income countries. This appears to be due to a combination of improved treatment following a cardiovascular event and reduced risk factors, including LDL-cholesterol. Whether this reduction is due to changes in dietary habits, or the increasing availability of highly potent cholesterol-reducing drugs remains to be firmly established. While reducing dietary SFA intake has been the cornerstone of public health nutrition policy for several decades, the efficacy of such dietary changes has been challenged in recent years. While there remains a lack of consensus in the literature, there is an emerging view that dietary advice should be specifically modified to emphasise replacing SFA with PUFA in the diet rather than carbohydrate. The advice to moderate dietary SFA intake given to the general population is usually also given to those individuals at high risk of CVD who are prescribed lipid-lowering drugs. There is limited evidence to suggest that any potential benefit of such a diet on LDL-cholesterol may be offset by a concurrent decrease in HDL-cholesterol. However, as diets rich in SFA are frequently energy-dense, and rich in red and processed meat (potential risk factors for CVD in themselves), it would seem prudent to continue to advise patients on lipid-lowering drugs to maintain a low-fat diet.
Background: Heterozygous loss-of-function mutations in the synaptic scaffolding gene SHANK2 are strongly associated with autism spectrum disorder (ASD). However, their impact on the function of human neurons is unknown. Derivation of induced pluripotent stem cells (iPSC) from affected individuals permits generation of live neurons to answer this question. Methods: We generated iPSCs by reprogramming dermal fibroblasts of neurotypic and ASD-affected donors. To isolate the effect of SHANK2, we used CRISPR/Cas9 to knock out SHANK2 in control iPSCs and correct a heterozygous nonsense mutation in ASD-affected donor iPSCs. We then derived cortical neurons from SOX1+ neural precursor cells differentiated from these iPSCs. Using a novel assay that overcomes line-to-line variability, we compared neuronal morphology, total synapse number, and electrophysiological properties between SHANK2 mutants and controls. Results: Relative to controls, SHANK2 mutant neurons have increased dendrite complexity, dendrite length, total synapse number (1.5-2-fold), and spontaneous excitatory postsynaptic current (sEPSC) frequency (3-7.6-fold). Conclusions: ASD-associated heterozygous loss-of-function mutations in SHANK2 increase synaptic connectivity among human neurons by increasing synapse number and sEPSC frequency. This is partially supported by increased dendrite length and complexity, providing evidence that SHANK2 functions as a suppressor of dendrite branching during neurodevelopment.
The final stages of low-mass stellar evolution are characterized by significant mass loss due to stellar pulsations during the AGB phase, which lead to the development of planetary nebulae. Molecular masers of H2O, SiO, and ground state OH transitions are commonly detected in oxygen-rich late-type stars (OH/IR objects). In contrast, excited OH maser transitions are rare. We discuss our study of the carbon-rich pre-planetary nebula CRL618 (a prototypical post-AGB star). Observations conducted in May 2008 with the 305m Arecibo Telescope resulted in the first detection of a 4765MHz OH maser line in a late-type stellar object; the detection was confirmed a few months later also with Arecibo. Subsequent observations in 2015 and 2017 resulted in non-detection of the 4765MHz OH line. Our observations indicate that the 4765MHz OH maser in CRL 618 is highly variable, possibly tracing a short-lived phenomenon during the development of a pre-planetary nebula.
Nutrition during pregnancy can impact on the susceptibility of the offspring to CVD. Postnatal consumption of trans-fatty acids (TFA), associated with partially hydrogenated vegetable oil (PHVO), increases the risk of atherosclerosis, whereas evidence for those TFA associated with ruminant-derived dairy products and meat remain equivocal. In this study, we investigate the impact of maternal consumption of dietary PHVO (P) and ruminant milk fat (R) on the development of atherosclerosis in their offspring, using the transgenic apoE*3 Leiden mouse. Dams were fed either chow (C) or one of three high-fat diets: a diet reflecting the SFA content of a ‘Western’ diet (W) or one enriched with either P or R. Diets were fed during either pregnancy alone or pregnancy and lactation. Weaned offspring were then transferred to an atherogenic diet for 12 weeks. Atherosclerosis was assessed as lipid staining in cross-sections of the aorta. There was a significant effect of maternal diet during pregnancy on development of atherosclerosis (P=0·013) in the offspring with those born of mothers fed R or P during pregnancy displaying smaller lesions that those fed C or W. This was not associated with changes in total or lipoprotein cholesterol. Continuing to feed P during lactation increased atherosclerosis compared with that seen in offspring of dams fed P only during pregnancy (P<0·001). No such effect was seen in those from mothers fed R (P=0·596) or W (P=901). We conclude that dietary TFA have differing effects on cardiovascular risk at different stages of the lifecycle.
Global demand for meat and dairy products has increased dramatically in recent decades and, through a combination of global population growth, increased lifespan and improved economic prosperity in the developing world will inevitably continue to increase. The predicted increases in livestock production will put a potentially unsustainable burden on global resources, including land for production of crops required for animal feed and fresh water. Furthermore, animal production itself is associated with greenhouse gas production, which may speed up global warming and thereby impact on our ability to produce food. There is, therefore, an urgent need to find methods to improve the sustainability of livestock production. This review will consider various options for improving the sustainability of livestock production with particular emphasis on finding ways to replace conventional crops as sources of animal feeds. Alternatives, such as currently underutilised crops (grown on a marginal land) and insects, reared on substrates not suitable for direct consumption by farm animals, represent possible solutions. Coupled with a moderation of excessive meat consumption in wealthier countries, such strategies may secure the long-term sustainability of meat and milk production and mitigate against the adverse health effects of excessive intake.
Introduction: Point of care ultrasound (PoCUS) provides invaluable information during resuscitation efforts in cardiac arrest by determining presence/absence of cardiac activity and identifying reversible causes such as pericardial tamponade. There is no agreed guideline on how to safely and effectively incorporate PoCUS into the advanced cardiac life support (ACLS) algorithm. We consider that a consensus-based priority checklist using a “4 F’s” approach (Fluid; Form; Function; Filling), would provide a better algorithm during ACLS. Methods: The ultrasound subcommittee of the Australasian College for Emergency Medicine (ACEM) drafted a checklist incorporating PoCUS into the ACLS algorithm. This was further developed using the input of 24 international experts associated with five professional organizations led by the International Federation of Emergency Medicine. A modified Delphi tool was developed to reach an international consensus on how to integrate ultrasound into cardiac arrest algorithms for emergency department patients. Results: Consensus was reached following 3 rounds. The agreed protocol focuses on the timing of PoCUS as well as the specific clinical questions. Core cardiac windows performed during the rhythm check pause in chest compressions are the sub-xiphoid and parasternal cardiac views. Either view should be used to detect pericardial fluid, as well as examining ventricular form (e.g. right heart strain) and function, (e.g. asystole versus organized cardiac activity). Supplementary views include lung views (for absent lung sliding in pneumothorax and for pleural fluid), and IVC views for filling. Additional ultrasound applications are for endotracheal tube confirmation, proximal leg veins for DVT, or for sources of blood loss (AAA, peritoneal/pelvic fluid). Conclusion: The authors hope that this process will lead to a consensus-based SHoC-cardiac arrest guideline on incorporating PoCUS into the ACLS algorithm.
Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high-fat diet in utero, programed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28 days postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (P<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol; however, transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared with wild-type controls (P=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R2=0.563, P<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol two-fold higher than in chow-fed mothers, P=0.011). The data strongly suggest that maternal hypercholesterolemia programs later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models.
We present global VLBI and VLBA observations of the compact steep spectrum quasar B1524–136. These observations reveal well-defined radio jets on both sides of the active nucleus. Also, the overall radio structure appears highly distorted and asymmetric with the counter-jet exhibiting several oscillations. A possible scenario is one in which jet and counter-jet are inclined at about 25° and 75° to the line of sight respectively and an environment which is dense on the jet side. Possible implications of these results are discussed.
In 1991, the Committee on Medical Aspects of Food Policy produced a report on the dietary reference values for food energy and nutrients for groups of people in the United Kingdom. The resulting recommendations, which included specific limits for intakes of total, saturated, trans- and cis-polyunsaturated fatty acids (PUFA) have remained a cornerstone of public health policy ever since, and similar recommendations have been adopted by the World Health Organization. These recommendations were made largely on the basis of specific effects of these fatty acids on the risk of developing atherosclerotic cardiovascular disease (CVD). The intervening years have seen a plethora of human epidemiological and intervention trials to further elucidate the specific relationship between dietary fatty acid intake, plasma lipids and lipoproteins and cardiovascular morbidity and mortality. A number of recent meta-analyses and systematic reviews have revisited the role of specific dietary fatty acid classes and CVD risk. In general, these continue to support a link between saturated fatty acids (SFA) and CVD morbidity/mortality. They also highlight the potent adverse effects of trans fatty acids derived from partially hydrogenated vegetable oil. The most recent data suggest that replacing SFA with cis-PUFA (primarily linoleic acid) has the greatest impact on reducing CVD risk. Evidence of specific beneficial effects of n-3 PUFA is generally stronger for secondary, rather than primary, CVD risk, and it is restricted to very long chain fatty acids of marine origin as opposed to alpha-linolenic acid. Taken together, these data suggest that recent focus on dietary n-6-to-n-3 PUFA ratios may have been misguided, and that future strategies should focus on replacing dietary SFA with total PUFA, rather than concentrating on n-6 : n-3 PUFA ratio.
Understanding the deformation mechanisms that may operate in pyrite (FeS2) across a range of P-Tconditions is important in deciphering the history of deformed ore deposits. Pyrite has frequently been considered a hard mineral, which deforms by cataclastic flow or diffusive processes, if at all, at temperatures <425°C. However, utilizing SEM-based orientation-contrast (OC) imaging and electron-backscatter diffraction (EBSD) techniques, plastic deformation can now be readily identified within pyrite grains. In this study, a series of pyrite-rich polymetallic ore deposits, deformed at low temperature metamorphic conditions (∼200—420°C), have been investigated. Results indicate that pyrite grains in all the ore deposits preserve internal lattice ‘distortion’ or ‘bending’ and therefore plastic deformation mechanisms have operated. Many pyrite grains in the ore deposits also contain low-angle (∼2°) sub-grain boundaries or ‘dislocation walls', indicating that both dislocation glide and creep have been the dominant deformation mechanisms at peak metamorphic conditions within the pyrite grains. These results suggest that the brittle-ductile transition in pyrite occurs at temperatures potentially as low as ∼200°C, far lower than implied from previous studies or the current pyrite deformation-mechanism map.
Highly pathogenic avian influenza (HPAI) subtype H5N1 remains a public health threat as long as it circulates in wild and domestic birds. Information on the transmissibility of H5N1 HPAI from wild birds is needed for evidence-based public health advice. We investigated if transmission of H5N1 HPAI had taken place in people that had unprotected contact with infected wild mute swans during an incident at the Abbotsbury Swannery in Dorset, England. Thirteen people who had been exposed to infected swans were contacted and actively followed up for symptoms. Serology was taken after 30 days. We did not find evidence of transmission of H5N1 HPAI to humans during the incident. The incident provided a rare opportunity to study the transmissibility of the virus from wild birds to humans.
Dietary conjugated linoleic acids (CLA) have been reported to have a number of isomer-dependent effects on lipid metabolism including reduction in adipose tissue deposition, changes in plasma lipoprotein concentrations and hepatic lipid accumulation. The aim of this study was to compare the effect of individual CLA isomers against lipogenic and high ‘Western’ fat background diets. Golden Syrian hamsters were fed a high-carbohydrate rodent chow or chow supplemented with 17·25 % fat formulated to represent the type and amount of fatty acids found in a typical ‘Western’ diet (including 0·2 % cholesterol). Diets were further supplemented with 0·25 % (w/w) rapeseed oil, cis9, trans11 (c9,t11)-CLA or trans10, cis12 (t10,c12)-CLA. Neither isomer had a significant impact on plasma lipid or lipoprotein concentrations. The t10,c12-CLA isomer significantly reduced perirenal adipose tissue depot mass. While adipose tissue acetyl CoA carboxylase and fatty acid synthase mRNA concentrations (as measured by quantitative PCR) were unaffected by CLA, lipoprotein lipase mRNA was specifically reduced by t10,c12-CLA, on both background diets (P < 0·001). This was associated with a specific reduction of sterol regulatory element binding protein 1c expression in perirenal adipose tissue (P = 0·018). The isomers appear to have divergent effects on liver TAG content with c9,t11-CLA producing lower concentrations than t10,c12-CLA. We conclude that t10,c12-CLA modestly reduces adipose tissue deposition in the Golden Syrian hamster independently of background diet and this may possibly result from reduced uptake of lipoprotein fatty acids, as a consequence of reduced lipoprotein lipase gene expression.
Poor quality of nutrition during fetal development is associated with adverse health outcomes in adult life. Epidemiological studies suggest that markers of fetal undernutrition are predictive of risk of the metabolic syndrome and CHD. Here we show that feeding a low-protein diet during pregnancy programmed the development of atherosclerosis in ApoE*3-Leiden mice. ApoE*3-Leiden mice carry a mutation of human ApoE*3 rendering them prone to atherosclerosis when fed a diet rich in cholesterol. It was noted that fetal exposure to protein restriction led to a greater degree of dyslipidaemia in mice when fed an atherogenic diet, with low-protein-exposed ApoE*3 mice having elevated total plasma cholesterol (34 % higher; P < 0·001) and TAG (39 % higher; P < 0·001) relative to offspring exposed to a control diet in utero. The low-protein group developed more severe atherosclerotic lesions within the aortic arch (2·61-fold greater lesion area; P < 0·001). Analysis of a targeted gene array suggested a potential role for members of the LDL receptor superfamily, along with similar programmed suppression of the mRNA expression of hepatic sterol regulatory element-binding protein-1c. This indicates that disordered lipid metabolism may play a role in the fetal programming of atherosclerosis in this model. Whereas earlier studies have shown early programming of cardiovascular risk factors, these results demonstrate for the first time that the interaction of prenatal undernutrition with a postnatal atherogenic diet increases the extent of atherosclerotic disease.