Understanding a Low Vitamin D State in the Context of COVID-19

While a low vitamin D state has been associated with an increased risk of infection by SARS-CoV-2 in addition to an increased severity of COVID-19 disease, a causal role is not yet established. Here, we review the evidence relating to i) vitamin D and its role in SARS-CoV-2 infection and COVID-19 disease ii) the vitamin D status in the Irish adult population iii) the use of supplemental vitamin D to treat a deficient status and iv) the application of the Bradford-Hill causation criteria. We conclude that reverse causality probably makes a minimal contribution to the presence of low vitamin D states in the setting of COVID-19. Applying the Bradford-Hill criteria, however, the collective literature supports a causal association between low vitamin D status, SARS-CoV-2 infection, and severe COVID-19 (respiratory failure, requirement for ventilation and mortality). A biologically plausible rationale exists for these findings, given vitamin D’s role in immune regulation. The thresholds which define low, deficient, and replete vitamin D states vary according to the disease studied, underscoring the complexities for determining the goals for supplementation. All are currently unknown in the setting of COVID-19. The design of vitamin D randomised controlled trials is notoriously problematic and these trials commonly fail for a number of behavioural and methodological reasons. In Ireland, as in most other countries, low vitamin D status is common in older adults, adults in institutions, and with obesity, dark skin, low UVB exposure, diabetes and low socio-economic status. Physiological vitamin D levels for optimal immune function are considerably higher than those that can be achieved from food and sunlight exposure alone in Ireland. A window exists in which a significant number of adults could benefit from vitamin D supplementation, not least because of recent data demonstrating an association between vitamin D status and COVID-19. During the COVID pandemic, we believe that supplementation with 20-25ug (800–1000 IU)/day or more may be required for adults with apparently normal immune systems to improve immunity against SARS-CoV-2. We expect that higher monitored doses of 37.5–50 ug (1,500–2,000)/day may be needed for vulnerable groups (e.g., those with obesity, darker skin, diabetes mellitus and older adults). Such doses are within the safe daily intakes cited by international advisory agencies

A quasi-synoptic survey of the thermocline circulation and water mass distribution within the Canary Basin

Shipboard hydrographic measurements and moored current meters are used to infer both the large-scale and mesoscale water mass distribution and features of the general circulation in the Canary Basin. We found a convoluted current system dominated by the time-dependent meandering of the eastward flowing Azores Current and the formation of mesoscale eddies. At middepths, several distinctly different water masses are identified: Subpolar Mode and Labrador Sea Water are centered in the northwest, Subantarctic Intermediate Water is centered in the southeast, and the saltier, warmer Mediterranean tongue lies between them. Mesoscale structures of these water masses suggest the presence of middepth meanders and detached eddies which may be caused by fluctuations of the Azores Current

Epigenome-Wide Association Study of Kidney Function Identifies Trans-Ethnic and Ethnic-Specific Loci

BACKGROUND: DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach. METHODS: The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses. RESULTS: We identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development. CONCLUSIONS: We uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context

Will Exercise Advice Be Sufficient for Treatment of Young Adults With Prehypertension and Hypertension?:A Systematic Review and Meta-Analysis

Previous studies report benefits of exercise for blood pressure control in middle age and older adults, but longer-term effectiveness in younger adults is not well established. We performed a systematic review and meta-analysis of published randomized control trials with meta-regression of potential effect modifiers. An information specialist completed a comprehensive search of available data sources, including studies published up to June 2015. Authors applied strict inclusion and exclusion criteria to screen 9524 titles. Eligible studies recruited younger adults with a cardiovascular risk factor (with at least 25% of cohort aged 18 to 40 years); the intervention had a defined physical activity strategy and reported blood pressure as primary or secondary outcome. Meta-analysis included 14 studies randomizing 3614 participants, mean age 42.2+/-6.3 (sd) years. At 3 to 6 months, exercise was associated with a reduction in systolic blood pressure of –4.40 mmHg (95%CI, -5.78 to -3.01) and in diastolic blood pressure of -4.17 mmHg (95%CI, -5.42 to -2.93). Intervention effect was not significantly influenced by baseline blood pressure, body weight or subsequent weight loss. Observed intervention effect was lost after 12 months follow-up with no reported benefit over control, mean difference in systolic blood pressure -1.02 mmHg (95%CI, -2.34 to 0.29) and in diastolic blood pressure –0.91 mmHg (95%CI, -1.85 to 0.02). Current exercise guidance provided to reduce blood pressure in younger adults is unlikely to benefit long-term cardiovascular risk. There is need for continued research to improve age specific strategies and recommendations for hypertension prevention and management in young adults

Hydrographic changes in the eastern subpolar North Atlantic during the last deglaciation

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Quaternary Science Reviews 29 (2010): 3336-3345, doi:10.1016/j.quascirev.2010.08.013.Millennial-scale climate fluctuations of the last deglaciation have been tied to abrupt changes in the Atlantic Meridional Overturning Circulation (MOC). A key to understanding mechanisms of MOC collapse and recovery is the documentation of upper ocean hydrographic changes in the vicinity of North Atlantic deep convection sites. Here we present new high-resolution ocean temperature and δ18Osw records spanning the last deglaciation from an eastern subpolar North Atlantic site that lies along the flow path of the North Atlantic Current, approaching deep convection sites in the Labrador and Greenland-Iceland-Norwegian (GIN) Seas. High-resolution temperature and δ18Osw records from subpolar Site 980 help track the movement of the subpolar/subtropical front associated with temperature and Atlantic MOC changes throughout the last deglaciation. Distinct δ18Osw minima during Heinrich-1 (H1) and the Younger Dryas (YD) correspond with peaks in ice-rafted debris and periods of reduced Atlantic MOC, indicating the presence of melt water in this region that could have contributed to MOC reductions during these intervals. Increased tropical and subtropical δ18Osw during these periods of apparent freshening in the subpolar North Atlantic suggest a buildup of salt at low latitudes that served as a negative feedback on reduced Atlantic MOC.Support for this research was provided by the U.S. National Science Foundation (JFM and DWO) and a postdoctoral scholarship funded in part by the Gary Comer Science and Education Foundation (HB)

Adenomatous polyposis coli protein nucleates actin assembly and synergizes with the formin mDia1

The microtubule regulator APC is now shown to also regulate actin filament dynamics through its C-terminal “Basic” domain