A cautionary tale of low-pass sequencing and imputation with respect to haplotype accuracy.

BACKGROUND: Low-pass whole-genome sequencing and imputation offer significant cost savings, enabling substantial increases in sample size and statistical power. This approach is particularly promising in livestock breeding, providing an affordable means of screening individuals for deleterious alleles or calculating genomic breeding values. Consequently, it may also be of value in companion animal genomics to support pedigree breeding. We sought to evaluate in dogs the impact of low coverage sequencing and reference-guided imputation on genotype concordance and association analyses. RESULTS: DNA isolated from saliva of 30 Labrador retrievers was sequenced at low (0.9X and 3.8X) and high (43.5X) coverage, and down-sampled from 43.5X to 9.6X and 17.4X. Genotype imputation was performed using a diverse reference panel (1021 dogs), and two subsets of the former panel (256 dogs each) where one had an excess of Labrador retrievers relative to other breeds. We observed little difference in imputed genotype concordance between reference panels. Association analyses for a locus acting as a disease proxy were performed using single-marker (GEMMA) and haplotype-based (XP-EHH) tests. GEMMA results were highly correlated (r ≥ 0.97) between 43.5X and ≥ 3.8X depths of coverage, while for 0.9X the correlation was lower (r ≤ 0.8). XP-EHH results were less well correlated, with r ranging from 0.58 (0.9X) to 0.88 (17.4X). Across a random sample of 10,000 genomic regions averaging 17 kb in size, we observed a median of three haplotypes per dog across the sequencing depths, with 5% of the regions returning more than eight haplotypes. Inspection of one such region revealed genotype and phasing inconsistencies across sequencing depths. CONCLUSIONS: We demonstrate that saliva-derived canine DNA is suitable for whole-genome sequencing, highlighting the feasibility of client-based sampling. Low-pass sequencing and imputation require caution as incorrect allele assignments result when the subject possesses alleles that are absent in the reference panel. Larger panels have the capacity for greater allelic diversity, which should reduce the potential for imputation error. Although low-pass sequencing can accurately impute allele dosage, we highlight issues with phasing accuracy that impact haplotype-based analyses. Consequently, if accurately phased genotypes are required for analyses, we advocate sequencing at high depth (> 20X).

Gsx2, but not Gsx1, is necessary for early forebrain patterning and long-term survival in zebrafish.

BACKGROUND: Homeobox transcription factor encoding genes, genomic screen homeobox 1 and 2 (gsx1 and gsx2), are expressed during neurodevelopment in multiple vertebrates. However, we have limited knowledge of the dynamic expression of these genes through developmental time and the gene networks that they regulate in zebrafish. RESULTS: We confirmed that gsx1 is expressed initially in the hindbrain and diencephalon and later in the optic tectum, pretectum, and cerebellar plate. gsx2 is expressed in the early telencephalon and later in the pallium and olfactory bulb. gsx1 and gsx2 are co-expressed in the hypothalamus, preoptic area, and hindbrain, however, rarely co-localize in the same cells. gsx1 and gsx2 mutant zebrafish were made with TALENs. gsx1 mutants exhibit stunted growth, however, they survive to adulthood and are fertile. gsx2 mutants experience swim bladder inflation failure that prevents survival. We also observed significantly reduced expression of multiple forebrain patterning distal-less homeobox genes in mutants, and expression of foxp2 was not significantly affected. CONCLUSIONS: This work provides novel tools with which other target genes and functions of Gsx1 and Gsx2 can be characterized across the central nervous system to better understand the unique and overlapping roles of these highly conserved transcription factors.

Mercury Bioaccumulation and Cortisol Interact to Influence Endocrine and Immune Biomarkers in a Free-Ranging Marine Mammal.

Mercury bioaccumulation from deep-ocean prey and the extreme life history strategies of adult female northern elephant seals (Mirounga angustirostris) provide a unique system to assess the interactive effects of mercury and stress on animal health by quantifying blood biomarkers in relation to mercury (skeletal muscle and blood mercury) and cortisol concentrations. The thyroid hormone thyroxine (tT4) and the antibody immunoglobulin E (IgE) were associated with mercury and cortisol concentrations interactively, where the magnitude and direction of the association of each biomarker with mercury or cortisol changed depending on the concentration of the other factor. For example, when cortisol concentrations were lowest, tT4 was positively related to muscle mercury, whereas tT4 had a negative relationship with muscle mercury in seals that had the highest cortisol concentrations. Additionally, we observed that two thyroid hormones, triiodothyronine (tT3) and reverse triiodothyronine (rT3), were negatively (tT3) and positively (rT3) associated with mercury concentrations and cortisol in an additive manner. As an example, tT3 concentrations in late breeding seals at the median cortisol concentration decreased by 14% across the range of observed muscle mercury concentrations. We also observed that immunoglobulin M (IgM), the pro-inflammatory cytokine IL-6 (IL-6), and a reproductive hormone, estradiol, were negatively related to muscle mercury concentrations but were not related to cortisol. Specifically, estradiol concentrations in late molting seals decreased by 50% across the range of muscle mercury concentrations. These results indicate important physiological effects of mercury on free-ranging apex marine predators and interactions between mercury bioaccumulation and extrinsic stressors. Deleterious effects on animals' abilities to maintain homeostasis (thyroid hormones), fight off pathogens and disease (innate and adaptive immune system), and successfully reproduce (endocrine system) can have significant individual- and population-level consequences.

Age- and Sex-Varying Associations Between Depressive Symptoms and Substance Use from Modal Ages 35 to 55 in a National Sample of U.S. Adults.

It is important to examine normative age-related change in substance use risk factors across the lifespan, with research focusing on middle adulthood particularly needed. The current study examined time-varying associations between depressive symptoms and alcohol, cigarette, and marijuana use from modal ages 35 to 55 in a national sample of US adults, overall and by sex. Data were obtained from 11,147 individuals in the longitudinal Monitoring the Future study. Participants were in 12th grade (modal age 18) in 1976-1982 and (for the data reported in this study) were surveyed again at modal ages 35 (in 1993-1999), 40, 45, 50, and 55 (in 2013-2019). Weighted time-varying effect modeling was used to examine age-related change in associations among depressive symptoms, any and heavy use of cigarettes, alcohol, and marijuana. Across midlife, greater depressive symptoms were associated with decreased odds of any alcohol use during the 40 s and 50 s, but with increased odds of binge drinking from ages 35-40, and-at most ages-any and pack + cigarette use and any and frequent marijuana use. The association between depressive symptoms and substance use was generally similar for men and women. Results highlight the increased risk for binge drinking, smoking, and marijuana with higher levels of depressive symptoms and underscore the importance of screening and interventions for depressive symptoms and substance use in midlife.

Avian influenza antibody prevalence increases with mercury contamination in wild waterfowl.

Environmental contamination is widespread and can negatively impact wildlife health. Some contaminants, including heavy metals, have immunosuppressive effects, but prior studies have rarely measured contamination and disease simultaneously, which limits our understanding of how contaminants and pathogens interact to influence wildlife health. Here, we measured mercury concentrations, influenza infection, influenza antibodies and body condition in 749 individuals from 11 species of wild ducks overwintering in California. We found that the odds of prior influenza infection increased more than fivefold across the observed range of blood mercury concentrations, while accounting for species, age, sex and date. Influenza infection prevalence was also higher in species with higher average mercury concentrations. We detected no relationship between influenza infection and body fat content. This positive relationship between influenza prevalence and mercury concentrations in migratory waterfowl suggests that immunotoxic effects of mercury contamination could promote the spread of avian influenza along migratory flyways, especially if influenza has minimal effects on bird health and mobility. More generally, these results show that the effects of environmental contamination could extend beyond the geographical area of contamination itself by altering the prevalence of infectious diseases in highly mobile hosts.

The Influence of Timing in Critical Care Nutrition.

Proper timing of critical care nutrition has long been a matter of controversy. Critical illness waxes and wanes in stages, creating a dynamic flux in energy needs that we have only begun to examine. Furthermore, response to nutrition support likely differs greatly at the level of the individual patient in regard to genetic status, disease stage, comorbidities, and more. We review the observational and randomized literature concerning timing in nutrition support, discuss mechanisms of harm in feeding critically ill patients, and highlight the role of precision nutrition for moving the literature beyond the realm of blunt population averages into one that accounts for the patient-specific complexities of critical illness and host genetics.

Concordance of Computed Tomography Regional Body Composition Analysis Using a Fully Automated Open-Source Neural Network versus a Reference Semi-Automated Program with Manual Correction.

Quick, efficient, fully automated open-source programs to segment muscle and adipose tissues from computed tomography (CT) images would be a great contribution to body composition research. This study examined the concordance of cross-sectional areas (CSA) and densities for muscle, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and intramuscular adipose tissue (IMAT) from CT images at the third lumbar (L3) between an automated neural network (test method) and a semi-automatic human-based program (reference method). Concordance was further evaluated by disease status, sex, race/ethnicity, BMI categories. Agreement statistics applied included Lin's Concordance (CCC), Spearman correlation coefficient (SCC), Sorensen dice-similarity coefficient (DSC), and Bland−Altman plots with limits of agreement (LOA) within 1.96 standard deviation. A total of 420 images from a diverse cohort of patients (60.35 ± 10.92 years; body mass index (BMI) of 28.77 ± 7.04 kg/m2; 55% female; 53% Black) were included in this study. About 30% of patients were healthy (i.e., received a CT scan for acute illness or pre-surgical donor work-up), while another 30% had a diagnosis of colorectal cancer. The CCC, SCC, and DSC estimates for muscle, VAT, SAT were all greater than 0.80 (>0.80 indicates good performance). Agreement analysis by diagnosis showed good performance for the test method except for critical illness (DSC 0.65−0.87). Bland−Altman plots revealed narrow LOA suggestive of good agreement despite minimal proportional bias around the zero-bias line for muscle, SAT, and IMAT CSA. The test method shows good performance and almost perfect concordance for L3 muscle, VAT, SAT, and IMAT per DSC estimates, and Bland−Altman plots even after stratification by sex, race/ethnicity, and BMI categories. Care must be taken to assess the density of the CT images from critically ill patients before applying the automated neural network (test method).

Prioritizing nutrition during recovery from critical illness.

PURPOSE OF REVIEW: Patients admitted to the intensive care unit (ICU) often experience a significant decline in nutritional status due to a combination of the physiologic response to critical illness and insufficient calorie intake. The majority of research related to nutrition interventions for this population focuses on nutrition support during the acute phase. Minimal attention is given to the nutritional status of ICU patients during the recovery phase. This review will describe calorie intake when ICU care ends, provide an overview of barriers that limit intake, and possible interventions to improve nutritional status. RECENT FINDINGS: Current evidence suggests patients are consuming < 60% of calorie requirements after extubation and ICU discharge. This inadequate calorie intake may exacerbate weight loss and muscle and fat wasting. Physiologic, physical, and cognitive manifestations of critical illness can lead to multiple issues that cause poor intake. Possible interventions to improve calorie intake include a patient-centered approach that utilizes oral nutrition supplements and enteral nutrition. SUMMARY: Consuming adequate caloric intake in the recovery phase of critical illness is essential for rehabilitation. A systematic, patient centered approach that includes close monitoring of calorie and protein and timely interventions may be the best method to improve overall intake.

Affect-Based Problem Drinking Risk: The Reciprocal Relationship between Affective Lability and Problem Drinking.

AIMS: Negative affect has been implicated in risk for the development of problematic drinking behavior. Furthermore, there is evidence for reciprocal relationships between negative affect and problem drinking, such that engagement in problem drinking also predicts increases in negative affect. However, affective models of risk often fail to consider affective lability-the experience of rapidly changing mood. Although affective lability appears to increase risk for problem drinking, it is unknown if this relationship persists above and beyond other affect-related constructs (e.g. depression, anxiety) and if it is reciprocal in nature. Accordingly, we used a longitudinal survey design to examine (a) if affective lability predicts problem drinking above and beyond depression and anxiety and (b) if affective lability and problem drinking demonstrate a reciprocal relationship. METHODS: First-year college students (n = 358) participated in a three wave longitudinal study. We constructed a structural equation model (SEM) of a random intercept cross-lagged panel model to test our hypotheses. RESULTS: Consistent with our hypotheses, affective lability predicted increases in problem drinking while anxiety and depression did not. Problem drinking and affective lability demonstrated a reciprocal relationship in which increases in one predicted increases in the other at subsequent time points. This relationship was present beyond the predictive effects of anxiety or depression. CONCLUSIONS: Affective lability appears to be an important affect-based predictor of problem drinking, and there may be a reciprocal, risk-enhancing relationship between affective lability and problem drinking.Components of negative affect, such as depression or anxiety, have been shown to predict risk for problem drinking, and vice versa. A less considered construct, affective lability, predicted problem drinking while anxiety and depression did not add any predictive power. Problem drinking and affective lability also appeared to demonstrate a reciprocal relationship.

Acceleration-triggered animal-borne videos show a dominance of fish in the diet of female northern elephant seals.

Knowledge of the diet of marine mammals is fundamental to understanding their role in marine ecosystems and response to environmental change. Recently, animal-borne video cameras have revealed the diet of marine mammals that make short foraging trips. However, novel approaches that allocate video time to target prey capture events is required to obtain diet information for species that make long foraging trips over great distances. We combined satellite telemetry and depth recorders with newly developed date-/time-, depth- and acceleration-triggered animal-borne video cameras to examine the diet of female northern elephant seals during their foraging migrations across the eastern North Pacific. We obtained 48.2 h of underwater video, from cameras mounted on the head (n=12) and jaw (n=3) of seals. Fish dominated the diet (78% of 697 prey items recorded) across all foraging locations (range: 37-55°N, 122-152°W), diving depths (range: 238-1167 m) and water temperatures (range: 3.2-7.4°C), while squid comprised only 7% of the diet. Identified prey included fish such as myctophids, Merluccius sp. and Icosteus aenigmaticus, and squid such as Histioteuthis sp., Octopoteuthis sp. and Taningia danae Our results corroborate fatty acid analysis, which also found that fish are more important in the diet, and are in contrast to stomach content analyses that found cephalopods to be the most important component of the diet. Our work shows that in situ video observation is a useful method for studying the at-sea diet of long-ranging marine predators.

Prolonged Cardiopulmonary Bypass is Associated With Endothelial Glycocalyx Degradation.

BACKGROUND: The endothelial glycocalyx (EG) is involved in critical regulatory mechanisms that maintain endothelial vascular integrity. We hypothesized that prolonged cardiopulmonary bypass (CPB) may be associated with EG degradation. We performed an analysis of soluble syndecan-1 levels in relation to duration of CPB, as well as factors associated with cell stress and damage, such as mitochondrial DNA (mtDNA) and inflammation. METHODS: Blood samples from subjects undergoing cardiac surgery with CPB (n = 54) were obtained before and during surgery, 4-8 h and 24 h after completion of CPB, and on postoperative day 4. Flow cytometry was used to determine subpopulations of white blood cells. Plasma levels of mtDNA were determined using quantitative polymerase chain reaction and plasma content of shed syndecan-1 was measured. To determine whether syndecan-1 was signaling white blood cells, the effect of recombinant syndecan-1 on mobilization of neutrophils from bone marrow was tested in mice. RESULTS: CPB is associated with increased mtDNA during surgery, increased syndecan-1 blood levels at 4-8 h, and increased white blood cell count at 4-8 h and 24 h. Correlation analysis revealed significant positive associations between time on CPB and syndecan-1 (rs = 0.488, P < 0.001) and level of syndecan-1 and neutrophil count (rs = 0.351, P = 0.038) at 4-8 h. Intravenous administration of recombinant syndecan-1 in mice resulted in a 2.5-fold increase in the number of circulating neutrophils, concurrent with decreased bone marrow neutrophil number. CONCLUSIONS: Longer duration of CPB is associated with increased plasma levels of soluble syndecan-1, a signal for EG degradation, which can induce neutrophil egress from the bone marrow. Development of therapy targeting EG shedding may be beneficial in patients with prolonged CPB.

Advances in abortion care technology and management.

PURPOSE OF REVIEW: To review emerging evidence specific to abortion care, including diagnostic testing and pain management. RECENT FINDINGS: Recent advances in abortion care include improvements in gestational age dating, Rh status testing, and pain management methods. When ultrasound technology is available, the use of crown-rump length (CRL)-based dating is more accurate up to 13 weeks and composite CRL and biometry between 13 and 14 weeks. Evidence supports using updated fetal foot length-to-gestational age reference ranges for postprocedure gestational age confirmation. Serum tests for two placental proteins, pregnancy-associated plasma protein A and a disintegrin and metalloproteinase 12, show potential for identifying pregnancies with gestational age more than 70 days. Early research using flow cytometry demonstrates that fetal RBC exposure after first-trimester uterine aspiration is insufficient to cause maternal Rh-sensitization, supporting elimination of Rh testing and anti-D-immunoglobulin provision prior to 8 weeks gestation. Recent studies exploring pain management strategies have not generated a standardized approach. Auricular acupuncture appears to be promising. SUMMARY: Emerging data on improvements in gestational age dating and eliminating laboratory testing prior to early abortion procedures could have important implications for expanding access to early abortion care and telemedicine. Person-centered, novel pain management modalities, such as auricular acupuncture, help to improve client experience, by addressing both pain and anxiety.

Combination of High-Calorie Delivery and Organ Failure Increases Mortality Among Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: Among critically ill patients, the benefits of nutrition support may vary depending on severity of organ dysfunction. The objective of the current article was to explore the relationship between organ failure and calories exposure with hospital mortality during the first week of acute respiratory distress syndrome. DESIGN: Retrospective observational study. SETTING: Single-center ICU. PATIENTS: Adults admitted to the ICU with a diagnosis of acute respiratory distress syndrome. INTERVENTIONS: Calorie delivery from enteral nutrition, parenteral nutrition, propofol, and dextrose containing fluids were collected for 7 days following intubation. Sequential Organ Failure Assessment score was calculated at ICU admit and for the same 7 days to describe organ dysfunction; four different Sequential Organ Failure Assessment variables were created 1) Sequential Organ Failure Assessment at ICU admit, 2) average Sequential Organ Failure Assessment for the first 7 days following intubation, 3) the highest Sequential Organ Failure Assessment for the first 7 days following intubation, and 4) change in Sequential Organ Failure Assessment from intubation to 7 days later. MEASUREMENTS AND MAIN RESULTS: A total of 298 patients were included. Sequential Organ Failure Assessment at ICU admit, average Sequential Organ Failure Assessment for the first 7 days following intubation, highest Sequential Organ Failure Assessment for the first 7 days following intubation, change in Sequential Organ Failure Assessment from intubation to 7 days later, and calorie delivery the first 7 days following intubation were all associated with increased likelihood of mortality. Compared with patients with low organ failure and low-calorie delivery, those with high-calorie delivery and low organ failure, low-calorie delivery and high organ failure, and the combination of both high organ failure with high-calorie delivery were associated with an incremental increase in the likelihood or mortality. CONCLUSIONS: Organ failure appears to modify the relationship between calorie exposure and ICU outcome. Additional research is needed to identify appropriate thresholds for safe calorie exposure with increased organ failure.

Notch2 and Proteomic Signatures in Mouse Neointimal Lesion Formation.

OBJECTIVE: Vascular remodeling is associated with complex molecular changes, including increased Notch2, which promotes quiescence in human smooth muscle cells. We used unbiased protein profiling to understand molecular signatures related to neointimal lesion formation in the presence or absence of Notch2 and to test the hypothesis that loss of Notch2 would increase neointimal lesion formation because of a hyperproliferative injury response. APPROACH AND RESULTS: Murine carotid arteries isolated at 6 or 14 days after ligation injury were analyzed by mass spectrometry using a data-independent acquisition strategy in comparison to uninjured or sham injured arteries. We used a tamoxifen-inducible, cell-specific Cre recombinase strain to delete the Notch2 gene in smooth muscle cells. Vessel morphometric analysis and immunohistochemical staining were used to characterize lesion formation, assess vascular smooth muscle cell proliferation, and validate proteomic findings. Loss of Notch2 in smooth muscle cells leads to protein profile changes in the vessel wall during remodeling but does not alter overall lesion morphology or cell proliferation. Loss of smooth muscle Notch2 also decreases the expression of enhancer of rudimentary homolog, plectin, and annexin A2 in vascular remodeling. CONCLUSIONS: We identified unique protein signatures that represent temporal changes in the vessel wall during neointimal lesion formation in the presence and absence of Notch2. Overall lesion formation was not affected with loss of smooth muscle Notch2, suggesting compensatory pathways. We also validated the regulation of known injury- or Notch-related targets identified in other vascular contexts, providing additional insight into conserved pathways involved in vascular remodeling.

Mobile technology for family planning.

PURPOSE OF REVIEW: To evaluate the recent literature on mobile health applications available to patients for contraception and abortion care. RECENT FINDINGS: Women are increasingly interested in contraceptive tools utilizing mobile technology, and a majority of women expect them to be science-based. The largest number of available mobile apps supports natural family planning methods, which is recognized as the least effective contraceptive method. Many available apps cannot be relied on for accurate, science-based pregnancy prevention methods. Further, there is a paucity of data regarding use of mobile technology for women seeking or receiving abortion. SUMMARY: Further research is needed to evaluate mobile health apps and how they can best provide patient consumers with accurate, evidence-based information to support the prevention of unintended pregnancy.

ErbB2 promotes endothelial phenotype of human left ventricular epicardial highly proliferative cells (eHiPC).

The adult human heart contains a subpopulation of highly proliferative cells. The role of ErbB receptors in these cells has not been studied. From human left ventricular (LV) epicardial biopsies, we isolated highly proliferative cells (eHiPC) to characterize the cell surface expression and function of ErbB receptors in the regulation of cell proliferation and phenotype. We found that human LV eHiPC express all four ErbB receptor subtypes. However, the expression of ErbB receptors varied widely among eHiPC isolated from different subjects. eHiPC with higher cell surface expression of ErbB2 reproduced the phenotype of endothelial cells and were characterized by endothelial cell-like functional properties. We also found that EGF/ErbB1 induces VEGFR2 expression, while ligands for both ErbB1 and ErbB3/4 induce expression of Tie2. The number of CD31posCD45neg endothelial cells is higher in LV biopsies from subjects with high ErbB2 (ErbB2high) eHiPC compared to low ErbB2 (ErbB2low) eHiPC. These findings have important implications for potential strategies to increase the efficacy of cell-based revascularization of the injured heart, through promotion of an endothelial phenotype in cardiac highly proliferative cells.

Multilevel Factors Affecting Time to Cancer Diagnosis and Care Quality in Botswana.

BACKGROUND: Cancer incidence is increasing in Africa, and the majority of patients are diagnosed with advanced disease, limiting treatment options and survival. We sought to understand care patterns and factors contributing to delayed diagnosis and treatment initiation among patients with cancer in Botswana. PATIENTS AND METHODS: We recruited 20 patients who were enrolled in a prospective cancer cohort in Botswana to a qualitative substudy that explored cancer care pathways and factors affecting cancer care access and quality. We conducted an in-depth interview with each participant between October 2014 and January 2015, using a a structured interview guide with questions about initial cancer symptoms, previous consultations, diagnosis, and care pathways. Medical records were used to confirm dates or treatment details when needed. RESULTS: Individual and interpersonal factors such as cancer awareness and social support facilitated care-seeking behaviors. However, patients experienced multiple delays in diagnosis and treatment because of provider and health system barriers. Health system factors, such as misdiagnosis, understaffed facilities, poor referral communication and scheduling, and inadequate laboratory reporting systems, affected access to and quality of cancer care. CONCLUSION: These findings highlight the need for interventions at the patient, provider, and health system levels to improve cancer care quality and outcomes in Botswana. Results also suggest that widespread cancer education has potential to promote early diagnosis through family and community networks. Identified barriers and facilitators suggest that interventions to improve community education and access to diagnostic technologies could help improve cancer outcomes in this setting. IMPLICATIONS FOR PRACTICE: The majority (54%) of patients with cancer in Botswana present with advanced-stage cancer despite universal access to free health care, limiting the options for treatment and decreasing the likelihood of positive treatment outcomes. To reduce time from symptom onset to cancer treatment initiation, causes of delay in cancer care trajectories must be identified. The narratives of the patients interviewed for this study give insight into psychosocial factors, outlooks on disease, lower-level provider delays, and health system barriers that contribute to substantial delays for patients with cancer in Botswana. Identification of problems and barriers is essential for development of effective interventions to mitigate these factors, in order to improve cancer outcomes in this population.

Foraging and fasting can influence contaminant concentrations in animals: an example with mercury contamination in a free-ranging marine mammal.

Large fluctuations in animal body mass in relation to life-history events can influence contaminant concentrations and toxicological risk. We quantified mercury concentrations in adult northern elephant seals (Mirounga angustirostris) before and after lengthy at sea foraging trips (n = 89) or fasting periods on land (n = 27), and showed that mercury concentrations in blood and muscle changed in response to these events. The highest blood mercury concentrations were observed after the breeding fast, whereas the highest muscle mercury concentrations were observed when seals returned to land to moult. Mean female blood mercury concentrations decreased by 30% across each of the two annual foraging trips, demonstrating a foraging-associated dilution of mercury concentrations as seals gained mass. Blood mercury concentrations increased by 103% and 24% across the breeding and moulting fasts, respectively, demonstrating a fasting-associated concentration of mercury as seals lost mass. In contrast to blood, mercury concentrations in female's muscle increased by 19% during the post-breeding foraging trip and did not change during the post-moulting foraging trip. While fasting, female muscle mercury concentrations increased 26% during breeding, but decreased 14% during moulting. Consequently, regardless of exposure, an animal's contaminant concentration can be markedly influenced by their annual life-history events.

Retrospective and Prospective Memory Among OEF/OIF/OND Veterans With a Self-Reported History of Blast-Related mTBI.

OBJECTIVES: To evaluate prospective and retrospective memory abilities in Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) Veterans with and without a self-reported history of blast-related mild traumatic brain injury (mTBI). METHODS: Sixty-one OEF/OIF/OND Veterans, including Veterans with a self-reported history of blast-related mTBI (mTBI group; n=42) and Veterans without a self-reported history of TBI (control group; n=19) completed the Memory for Intentions Test, a measure of prospective memory (PM), and two measures of retrospective memory (RM), the California Verbal Learning Test-II and the Brief Visuospatial Memory Test-Revised. RESULTS: Veterans in the mTBI group exhibited significantly lower PM performance than the control group, but the groups did not differ in their performance on RM measures. Further analysis revealed that Veterans in the mTBI group with current PTSD (mTBI/PTSD+) demonstrated significantly lower performance on the PM measure than Veterans in the control group. PM performance by Veterans in the mTBI group without current PTSD (mTBI/PTSD-) was intermediate between the mTBI/PTSD+ and control groups, and results for the mTBI/PTSD- group were not significantly different from either of the other two groups. CONCLUSIONS: Results suggest that PM performance may be a sensitive marker of cognitive dysfunction among OEF/OIF/OND Veterans with a history of self-reported blast-related mTBI and comorbid PTSD. Reduced PM may account, in part, for complaints of cognitive difficulties in this Veteran cohort, even years post-injury. (JINS, 2018, 24, 324-334).