The influence of ApoE genotype on the lipid profile and lipoproteins during normal pregnancy in a Southern African population

Background: Pregnancy is associated with increases in fasting triglycerides and total cholesterol.1 ApoE isoforms are known to influence the concentration of cholesterol, with apoE2 homozygosity lowering and apoE4 homozygosity raising the cholesterol concentration compared with E3 homozygosity.2 The lipid profiles ApoE status and prevalence of small dense LDL species were evaluated for subjects attending an antenatal clinic.Results: Samples from 690 women aged between 16 and 42 years of age were analyzed during and after pregnancy. The fasting plasma triglyceride concentration (in mmol/L) was significantly higher in pregnancy (median = 1.5, IQR 1.0-2.0 vs median = 0.6, IQR 0.5-0.8 respectively, p < 0.0001). Similarly, the total cholesterol (in mmol/L) was increased during pregnancy (median=4.1, IQR 3.6-4.7 vs median 3.5, IQR 3.1-3.5, respectively p=0.0167). The median LDL cholesterol and HDL cholesterol did not change. Higher proportions of small density LDL species were seen during pregnancy compared to after pregnancy. The distribution of the LDL species during pregnancy and 6 weeks post-partum were significantly different p<0.0001 with the smaller species being much higher during pregnancy.Conclusion: ApoE4 genotype was associated with increased total cholesterol and LDL cholesterol concentrations during pregnancy. Pregnancy results in a reversible remodeling of LDL to smaller species, the significance of which is unknown but mayindicate a predisposition to atherosclerosisKeywords: Apolipoprotein E. Lipids, pregnancy, small dense LDL species, African.Due to errors in the previous PDF especially in the 'Cite as' authors names, the PDF fulltext has been reloaded. This information is now correct

The influence of ApoE genotype on the lipid profile and lipoproteins during normal pregnancy in a Southern African population.

Background: Pregnancy is associated with increases in fasting triglycerides and total cholesterol. ApoE isoforms are known to influence the concentration of cholesterol, with apoE2 homozygosity lowering and apoE4 homozygosity raising the cholesterol concentration compared with E3 homozygosity. The lipid profiles ApoE status and prevalence of small dense LDL species were evaluated for subjects attending an antenatal clinic. Results: Samples from 690 women aged between 16 and 42 years of age were analyzed during and after pregnancy. The fasting plasma triglyceride concentration (in mmol/L) was significantly higher in pregnancy (median = 1.5, IQR 1.0-2.0 vs median = 0.6, IQR 0.5-0.8 respectively, p < 0.0001). Similarly, the total cholesterol (in mmol/L) was increased during pregnancy (median=4.1, IQR 3.6-4.7 vs median 3.5, IQR 3.1-3.5, respectively p=0.0167). The median LDL cholesterol and HDL cholesterol did not change. Higher proportions of small density LDL species were seen during pregnancy compared to after pregnancy. The distribution of the LDL species during pregnancy and 6 weeks post-partum were significantly different p<0.0001 with the smaller species being much higher during pregnancy. Conclusion: ApoE4 genotype was associated with increased total cholesterol and LDL cholesterol concentrations during pregnancy. Pregnancy results in a reversible remodeling of LDL to smaller species, the significance of which is unknown but may indicate a predisposition to atherosclerosi

Residents transitioning between hospital and care homes: protocol for codesigning a systems-level response to safety issues (SafeST study)

Introduction: The aim of this study is to develop a better understanding of incident reporting in relation to transitions in care between hospital and care home, and to codesign a systems- level response to safety issues for patients transitioning between hospital and care home. Methods and analysis: Two workstreams (W) will run in parallel. W1 will aim to develop a taxonomy of incident reporting in care homes, underpinned by structured interviews (N=150) with care home representatives, scoping review of care home incident reporting systems, and a review of incident reporting policy related to care homes. The taxonomy will be developed using a standardised approach to taxonomy development. W2 will be structured in three phases (P). P1a will consist of ≤40 interviews with care home staff to develop a better understanding of their specific internal systems for reporting incidents, and P1b will include ≤30 interviews with others involved in transitions between hospital and care home. P1a and P1b will also examine the impact of the SARS- CoV- 2 pandemic on safe transitions. P2 will consist of a retrospective documentary analysis of care home data relating to resident transitions, with data size and sampling determined based on data sources identified in P1a. A validated data extraction form will be adapted before use. P3 will consist of four validation and codesign workshops to develop a service specification using National Health Service Improvement’s service specification framework, which will then be mapped against existing systems and recommendations produced. Framework analysis informed by the heuristic of systemic risk factors will be the primary mode of analysis, with content analysis used for analysing incident reports. Ethics and dissemination: The study has received university ethical approval and Health Research Authority approval. Findings will be disseminated to commissioners, providers and regulators who will be able to use the codesigned service specification to improve integrated care

Invasions and Extinctions Reshape Coastal Marine Food Webs

The biodiversity of ecosystems worldwide is changing because of species loss due to human-caused extinctions and species gain through intentional and accidental introductions. Here we show that the combined effect of these two processes is altering the trophic structure of food webs in coastal marine systems. This is because most extinctions (∼70%) occur at high trophic levels (top predators and other carnivores), while most invasions are by species from lower trophic levels (70% macroplanktivores, deposit feeders, and detritivores). These opposing changes thus alter the shape of marine food webs from a trophic pyramid capped by a diverse array of predators and consumers to a shorter, squatter configuration dominated by filter feeders and scavengers. The consequences of the simultaneous loss of diversity at top trophic levels and gain at lower trophic levels is largely unknown. However, current research suggests that a better understanding of how such simultaneous changes in diversity can impact ecosystem function will be required to manage coastal ecosystems and forecast future changes

Effects of Trophic Skewing of Species Richness on Ecosystem Functioning in a Diverse Marine Community

Widespread overharvesting of top consumers of the world’s ecosystems has “skewed” food webs, in terms of biomass and species richness, towards a generally greater domination at lower trophic levels. This skewing is exacerbated in locations where exotic species are predominantly low-trophic level consumers such as benthic macrophytes, detritivores, and filter feeders. However, in some systems where numerous exotic predators have been added, sometimes purposefully as in many freshwater systems, food webs are skewed in the opposite direction toward consumer dominance. Little is known about how such modifications to food web topology, e.g., changes in the ratio of predator to prey species richness, affect ecosystem functioning. We experimentally measured the effects of trophic skew on production in an estuarine food web by manipulating ratios of species richness across three trophic levels in experimental mesocosms. After 24 days, increasing macroalgal richness promoted both plant biomass and grazer abundance, although the positive effect on plant biomass disappeared in the presence of grazers. The strongest trophic cascade on the experimentally stocked macroalgae emerged in communities with a greater ratio of prey to predator richness (bottom-rich food webs), while stronger cascades on the accumulation of naturally colonizing algae (primarily microalgae with some early successional macroalgae that recruited and grew in the mesocosms) generally emerged in communities with greater predator to prey richness (the more top-rich food webs). These results suggest that trophic skewing of species richness and overall changes in food web topology can influence marine community structure and food web dynamics in complex ways, emphasizing the need for multitrophic approaches to understand the consequences of marine extinctions and invasions

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe

Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10−8) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies

The Massachusetts universal health insurance law: A case study of making health care policy

This is a case study of the process in Massachusetts that led to An Act to Make Health Security Available to All Citizens of the Commonwealth and to Improve Hospital Financing in 1988. It is set within the historical framework of the political economy of health care in the United States. The health care product emerged in the commodity form, the health care sector grew to be one of the most highly profitable sectors of the economy. The financing system became enmeshed in capital-labor relations through the development of employment-based health insurance.^ The process in Massachusetts is analyzed through the role of capital, the working class and the State. The structurally powerful players include medical capital (hospitals, physicians, insurers, biomedical technology firms); nonmedical capital (traditional industries, manufacturing, large employers); competitive capital (small business); the working class (organized labor, low wage, disenfranchised); the State.^ In the 1980\u27s, hospital rates in Massachusetts far exceeded the nation. As a result of shifts in the structure of the economy, an increase in the number of uninsured workers, accelerated a cost-shift for hospital care to employers who provided employee health insurance. Fifteen months of political negotiating ensued, primarily between the hospitals and big business over the issue of uncompensated care, with the State attempting to achieve a settlement.^ On the surface the debate centered on ensuring universal access to health care. In reality, it was a battle between two factions of capital over who would pay the health care bill. In the end the hospitals got massive revenue increases and big capital had its cost liability capped. The State took over hundreds of millions of dollars in health care costs to glue the deal together.^ This study highlights the structural basis of power in capitalist society. The most powerful players, the hospitals, controlled the definition of the problem, and dictated the solutions. The State was forced to align itself with big capital in order to assert itself into the negotiations. The question of access to health care was irrelevant to the process and the outcome.