The Effect of an Early Education Program on Adult Health: The Carolina Abecedarian Project Randomized Controlled Trial

Objectives. We explored whether a successful randomized controlled trial of early education, the Carolina Abecedarian Project (ABC), which enrolled infants from 1972 to 1977 at the Frank Porter Graham Child Development Institute in Chapel Hill, North Carolina, improved health outcomes and behaviors by 21 years of age. Methods. ABC randomized 111 infants to receive an intensive early education program or nutritional supplements and parental counseling alone; participants have been followed to the present day. We examined the effect of ABC on health outcomes and behavioral risk factors when participants were aged 21 years, and then explored the mediators of this relationship. Results. Relative to the control group, the ABC treatment group was previously found to have improved cognition and educational attainment. We found that the intervention also improved heath (P = .05) and health behaviors (P = .03) when participants were aged 21 years. These improvements in behaviors were not mediated by IQ, math and reading scores at 15 years of age, educational attainment, or health insurance. Conclusions. Effective early education programs may improve health and reduce risky health behaviors in adulthood

Acoustic and Seismic Fields of Hydraulic Jumps at Varying Froude Numbers

Mechanisms that produce seismic and acoustic wavefields near rivers are poorly understood because of a lack of observations relating temporally dependent river conditions to the near-river seismoacoustic fields. This controlled study at the Harry W. Morrison Dam (HWMD) on the Boise River, Idaho, explores how temporal variation in fluvial systems affects surrounding acoustic and seismic fields. Adjusting the configuration of the HWMD changed the river bathymetry and therefore the form of the standing wave below the dam. The HWMD was adjusted to generate four distinct wave regimes that were parameterized through their dimensionless Froude numbers (Fr) and observations of the ambient seismic and acoustic wavefields at the study site. To generate detectable and coherent signals, a standing wave must exceed a threshold Fr value of 1.7, where a nonbreaking undular jump turns into a breaking weak hydraulic jump. Hydrodynamic processes may partially control the spectral content of the seismic and acoustic energies. Furthermore, spectra related to reproducible wave conditions can be used to calibrate and verify fluvial seismic and acoustic models

Docosahexaenoic acid regulates the formation of lipid rafts: A unified view from experiment and simulation

Docosahexaenoic acid (DHA, 22:6) is an n-3 polyunsaturated fatty acid (n-3 PUFA) that influences immunological, metabolic, and neurological responses through complex mechanisms. One structural mechanism by which DHA exerts its biological effects is through its ability to modify the physical organization of plasma membrane signaling assemblies known as sphingomyelin/cholesterol (SM/chol)-enriched lipid rafts. Here we studied how DHA acyl chains esterified in the sn-2 position of phosphatidylcholine (PC) regulate the formation of raft and non-raft domains in mixtures with SM and chol on differing size scales. Coarse grained molecular dynamics simulations showed that 1-palmitoyl-2-docosahexaenoylphosphatylcholine (PDPC) enhances segregation into domains more than the monounsaturated control, 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC). Solid state 2H NMR and neutron scattering experiments provided direct experimental evidence that substituting PDPC for POPC increases the size of raft-like domains on the nanoscale. Confocal imaging of giant unilamellar vesicles with a non-raft fluorescent probe revealed that POPC had no influence on phase separation in the presence of SM/chol whereas PDPC drove strong domain segregation. Finally, monolayer compression studies suggest that PDPC increases lipid-lipid immiscibility in the presence of SM/chol compared to POPC. Collectively, the data across model systems provide compelling support for the emerging model that DHA acyl chains of PC lipids tune the size of lipid rafts, which has potential implications for signaling networks that rely on the compartmentalization of proteins within and outside of rafts

Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway.

A promising new compound class for treating human malaria is the imidazolopiperazines (IZP) class. IZP compounds KAF156 (Ganaplacide) and GNF179 are effective against Plasmodium symptomatic asexual blood-stage infections, and are able to prevent transmission and block infection in animal models. But despite the identification of resistance mechanisms in P. falciparum, the mode of action of IZPs remains unknown. To investigate, we here combine in vitro evolution and genome analysis in Saccharomyces cerevisiae with molecular, metabolomic, and chemogenomic methods in P. falciparum. Our findings reveal that IZP-resistant S. cerevisiae clones carry mutations in genes involved in Endoplasmic Reticulum (ER)-based lipid homeostasis and autophagy. In Plasmodium, IZPs inhibit protein trafficking, block the establishment of new permeation pathways, and cause ER expansion. Our data highlight a mechanism for blocking parasite development that is distinct from those of standard compounds used to treat malaria, and demonstrate the potential of IZPs for studying ER-dependent protein processing

Effect of Plain Versus Sugar-Sweetened Breakfast on Energy Balance and Metabolic Health : A Randomized Crossover Trial

We would like to thank Pippa Heath for her help with randomization, our participants, and Dr. Graham Horgan for statistical advice. Funding Information Economic and Social Research Council. Grant Number: ES/J50015X/1 Biotechnology and Biological Sciences Research Council (BBSRC) GlaxoSmithKline Lucozade Ribena Suntory Kellogg’s Nestlé PepsiCo Sugar Nutrition UK Danone Baby Nutrition the Alpro Foundation Kellogg Europe Unilever Volac International The Collagen Research Institute British Summer FruitsPeer reviewedPublisher PD

Sex and size influence the spatiotemporal distribution of white sharks, with implications for interactions with fisheries and spatial management in the southwest Indian Ocean

The study was made possible through generous funding by Fischer Productions for fieldwork and equipment costs. TP was supported by a postdoctoral fellowship funded by the Nelson Mandela University Research Career Development Office (2016-2018) and funding from the South African Research Chairs Initiative awarded to Prof AT Lombard by the National Research Foundation, and by a Royal Society Newton International Fellowship (2018-2020, NF170682).Human activities in the oceans increase the extinction risk of marine megafauna. Interventions require an understanding of movement patterns and the spatiotemporal overlap with threats. We analysed the movement patterns of 33 white sharks (Carcharodon carcharias) satellite-tagged in South Africa between 2012 and 2014 to investigate the influence of size, sex and season on movement patterns and the spatial and temporal overlap with longline and gillnet fisheries and marine protected areas (MPAs). We used a hidden Markov model to identify ‘resident’ and ‘transient’ movement states and investigate the effect of covariates on the transition probabilities between states. A model with sex, total length and season had the most support. Tagged sharks were more likely to be in a resident state near the coast and a transient state away from the coast, while the probability of finding a shark in the transient state increased with size. White sharks moved across vast areas of the southwest Indian Ocean, emphasising the need for a regional management plan. White sharks overlapped with longline and gillnet fisheries within 25% of South Africa’s Exclusive Economic Zone and spent 15% of their time exposed to these fisheries during the study period. The demersal shark longline fishery had the highest relative spatial and temporal overlap, followed by the pelagic longline fishery and the KwaZulu-Natal (KZN) shark nets and drumlines. However, the KZN shark nets and drumlines reported the highest white shark catches, emphasising the need to combine shark movement and fishing effort with reliable catch records to assess risks to shark populations accurately. White shark exposure to shark nets and drumlines, by movement state, sex and maturity status, corresponded with the catch composition of the fishery, providing support for a meaningful exposure risk estimate. White sharks spent significantly more time in MPAs than expected by chance, likely due to increased prey abundance or less disturbance, suggesting that MPAs can benefit large, mobile marine megafauna. Conservation of white sharks in Southern Africa can be improved by implementing non-lethal solutions to beach safety, increasing the observer coverage in fisheries, and continued monitoring of movement patterns and existing and emerging threats.Publisher PDFPeer reviewe

An Umbrella Review With Meta-Analysis of Chest Computed Tomography for Diagnosis of COVID-19: Considerations for Trauma Patient Management

BackgroundRT-PCR testing is the standard for diagnosis of COVID-19, although it has its suboptimal sensitivity. Chest computed tomography (CT) has been proposed as an additional tool with diagnostic value, and several reports from primary and secondary studies that assessed its diagnostic accuracy are already available. To inform recommendations and practice regarding the use of chest CT in the in the trauma setting, we sought to identify, appraise, and summarize the available evidence on the diagnostic accuracy of chest CT for diagnosis of COVID-19, and its application in emergency trauma surgery patients; overcoming limitations of previous reports regarding chest CT accuracy and discussing important considerations regarding its role in this setting.MethodsWe conducted an umbrella review using Living Overview of Evidence platform for COVID-19, which performs regular automated searches in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and more than 30 other sources. The review was conducted following the JBI methodology for systematic reviews. The Grading of Recommendations, Assessment, Development, and Evaluation approach for grading the certainty of the evidence is reported (registered in International Prospective Register of Systematic Reviews, CRD42020198267).ResultsThirty studies that fulfilled selection criteria were included; 19 primary studies provided estimates of sensitivity (0.91, 95%CI = [0.88–0.93]) and specificity (0.73, 95%CI = [0.61; 0.82]) of chest CT for COVID-19. No correlation was found between sensitivities and specificities (ρ = 0.22, IC95% [–0.33; 0.66]). Diagnostic odds ratio was estimated at: DOR = 27.5, 95%CI (14.7; 48.5). Evidence for sensitivity estimates was graded as MODERATE, and for specificity estimates it was graded as LOW.ConclusionThe value of chest CT appears to be that of an additional screening tool that can easily detect PCR false negatives, which are reportedly highly frequent. Upon the absence of PCR testing and impossibility to perform RT-PCR in trauma patients, chest CT can serve as a substitute with increased value and easy implementation.Systematic Review Registration[www.crd.york.ac.uk/prospero], identifier [CRD42020198267]

Protemic identification of Germline Proteins in Caenorhabditis elegans

Sexual reproduction involves fusion of 2 haploid gametes to form diploid offspring with genetic contributions from both parents. Gamete formation represents a unique developmental program involving the action of numerous germline-specific proteins. In an attempt to identify novel proteins involved in reproduction and embryonic development, we have carried out a proteomic characterization of the process in Caenorhabditis elegans. To identify candidate proteins, we used 2D gel electrophoresis (2DGE) to compare protein abundance in nucleus-enriched extracts from wild-type C. elegans, and in extracts from mutant worms with greatly reduced gonads (glp-4(bn2) worms reared at 25°C); 84 proteins whose abundance correlated with germline presence were identified. To validate candidates, we used feeding RNAi to deplete candidate proteins, and looked for reduction in fertility and/or germline cytological defects. Of 20 candidates so screened for involvement in fertility, depletion of 13 (65%) caused a significant reduction in fertility, and 6 (30%) resulted in sterility (\u3c5 % of wild-type fertility). Five of the 13 proteins with demonstrated roles in fertility have not previously been implicated in germline function. The high frequency of defects observed after RNAi depletion of candidate proteins suggests that this approach is effective at identifying germline proteins, thus contributing to our understanding of this complex organ