Lincoln, the Friendly Neighbor

The sculpture depicts a full-length Abraham Lincoln dressed in a suit. He stands with two children - male and female - and a dog. This particular sculpture is number one in a limited release of thirty.https://scholarsjunction.msstate.edu/fvw-artifacts/2377/thumbnail.jp

Lincoln, the Friendly Neighbor

The sculpture depicts a full-length Abraham Lincoln dressed in a suit. He stands with two children - male and female - and a dog. This particular sculpture is number one in a limited release of thirty.https://scholarsjunction.msstate.edu/fvw-statuettes-and-figurines/1031/thumbnail.jp

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Seasonal variations in exposure to methylmercury and its dietary sources among pregnant Inuit women in Nunavik, Canada

Among populations living in close connection with the sea, rivers and lakes for subsistence, diet varies according to local monthly wildlife species availability and food preferences. This may lead to variations in methylmercury (MeHg) exposure over a year, although no biomonitoring studies have documented this issue in Circumpolar populations, the most exposed to international Hg emissions. Our aim was to characterize seasonal variations in MeHg exposure among pregnant Inuit women from Nunavik and to identify country foods responsible for these variations. Between October 2016 and March 2017, 97 participants were recruited. Blood mercury (Hg) was tested and hair Hg was measured by centimeter as a surrogate for monthly MeHg exposure over the past year. Latent class growth analysis was conducted to identify groups of pregnant women with similar hair Hg monthly trajectories. Country foods consumption was documented by season. Seasonal daily intakes of MeHg were estimated based on concentrations in country foods. Retrospective monthly hair Hg analyses revealed that MeHg exposure was lowest in winter, and highest in summer and early fall months. Three latent classes (groups) of pregnant women with similar trajectories of monthly hair Hg variations were identified: high (n = 20, 21%), moderate (n = 38, 41%) and low variation (n = 35, 38%). Beluga meat was the country food contributing to most of daily MeHg intake, primarily during summer and fall, and was the only one associated with the odds of being classified into moderate and high variation groups (OR 95% CI: 1.19 [1.01–1.39] and 1.25 [1.04–1.50]). These findings underscore the importance of monthly variations in exposure to MeHg due to the seasonality of local foods consumed and responsible for elevated MeHg exposure. Further studies critically need to understand local diet fluctuations over a year to adequately assess MeHg exposure, adopt timely preventive interventions and evaluate the effectiveness of the Minamata Convention

Mutation analysis and characterization of ATR sequence variants in breast cancer cases from high-risk French Canadian breast/ovarian cancer families

BACKGROUND: Ataxia telangiectasia-mutated and Rad3-related (ATR) is a member of the PIK-related family which plays, along with ATM, a central role in cell-cycle regulation. ATR has been shown to phosphorylate several tumor suppressors like BRCA1, CHEK1 and TP53. ATR appears as a good candidate breast cancer susceptibility gene and the current study was designed to screen for ATR germline mutations potentially involved in breast cancer predisposition. METHODS: ATR direct sequencing was performed using a fluorescent method while widely available programs were used for linkage disequilibrium (LD), haplotype analyses, and tagging SNP (tSNP) identification. Expression analyses were carried out using real-time PCR. RESULTS: The complete sequence of all exons and flanking intronic sequences were analyzed in DNA samples from 54 individuals affected with breast cancer from non-BRCA1/2 high-risk French Canadian breast/ovarian families. Although no germline mutation has been identified in the coding region, we identified 41 sequence variants, including 16 coding variants, 3 of which are not reported in public databases. SNP haplotypes were established and tSNPs were identified in 73 healthy unrelated French Canadians, providing a valuable tool for further association studies involving the ATR gene, using large cohorts. Our analyses led to the identification of two novel alternative splice transcripts. In contrast to the transcript generated by an alternative splicing site in the intron 41, the one resulting from a deletion of 121 nucleotides in exon 33 is widely expressed, at significant but relatively low levels, in both normal and tumoral cells including normal breast and ovarian tissue. CONCLUSION: Although no deleterious mutations were identified in the ATR gene, the current study provides an haplotype analysis of the ATR gene polymorphisms, which allowed the identification of a set of SNPs that could be used as tSNPs for large-scale association studies. In addition, our study led to the characterization of a novel Δ33 splice form, which could generate a putative truncated protein lacking several functional domains. Additional studies in large cohorts and other populations will be needed to further evaluate if common and/or rare ATR sequence variants can be associated with a modest or intermediate breast cancer risk

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570