Greater stress and trauma mediate race-related differences in epigenetic age between Black and White young adults in a community sample.

Black Americans suffer lower life expectancy and show signs of accelerated aging compared to other Americans. While previous studies observe these differences in children and populations with chronic illness, whether these pathologic processes exist or how these pathologic processes progress has yet to be explored prior to the onset of significant chronic illness, within a young adult population. Therefore, we investigated race-related differences in epigenetic age in a cross-sectional sample of young putatively healthy adults and assessed whether lifetime stress and/or trauma mediate those differences. Biological and psychological data were collected from self-reported healthy adult volunteers within the local New Haven area (399 volunteers, 19.8% Black, mean age: 29.28). Stress and trauma data was collected using the Cumulative Adversity Inventory (CAI) interview, which assessed specific types of stressors, including major life events, traumatic events, work, financial, relationship and chronic stressors cumulatively over time. GrimAge Acceleration (GAA), determined from whole blood collected from participants, measured epigenetic age. In order to understand the impact of stress and trauma on GAA, exploratory mediation analyses were then used. We found cumulative stressors across all types of events (mean difference of 6.9 p = 2.14e-4) and GAA (ß = 2.29 years [1.57-3.01, p = 9.70e-10] for race, partial η2 = 0.091, model adjusted R2 = 0.242) were significantly greater in Black compared to White participants. Critically, CAI total score (proportion mediated: 0.185 [0.073-0.34, p = 6e-4]) significantly mediated the relationship between race and GAA. Further analysis attributed this difference to more traumatic events, particularly assaultive traumas and death of loved ones. Our results suggest that, prior to development of significant chronic disease, Black individuals have increased epigenetic age compared to White participants and that increased cumulative stress and traumatic events may contribute significantly to this epigenetic aging difference.

A Systems Approach to Remediating Human Exposure to Arsenic and Fluoride From Overexploited Aquifers.

In semiarid agricultural regions, aquifers have watered widespread economic development. Falling water tables, however, drive up energy costs and can make the water toxic for human consumption. The study area is located in central Mexico, where arsenic and fluoride are widely present at toxic concentrations in well water. We simulated the holistic outcomes from three pumping scenarios over 100 years (2020-2120); (S1) pumping rates increase at a similar rate to the past 40 years, (S2) remain constant, or (S3) decrease. Under scenario S1, by 2120, the depth to water table increased to 426 m and energy consumption for irrigation increased to 4 × 109 kWh/yr. Arsenic and fluoride concentrations increased from 14 to 46 µg/L and 1.0 to 3.6 mg/L, respectively. The combined estimated IQ point decrements from drinking untreated well water lowered expected incomes in 2120 by 27% compared to what they would be with negligible exposure levels. We calculated the 100-year Net Present Value (NPV) of each scenario assuming the 2020 average crop value to water footprint ratio of 0.12 USD/m3. Without drinking water mitigation, S1 and S3 yielded relative NPVs of -5.96 × 109 and 1.51 × 109 USD, respectively, compared to the base case (S2). The relative NPV of providing blanket reverse osmosis treatment, while keeping pumping constant (S2), was 11.55 × 109 USD and this gain increased when combined with decreased pumping (S3). If a high value, low water footprint crop was substituted (broccoli, 1.51 USD/m3), the net gains from increasing pumping were similar in size to those of implementing blanket drinking water treatment.

Ni-NTA Affinity Chromatography to Characterize Protein-Protein Interactions During Fe-S Cluster Biogenesis.

Affinity chromatography can be repurposed to provide useful information about the specific partner protein(s) to which a protein of interest may bind as well as the relative binding affinity of that partner protein for the protein of interest. Here, we provide a protocol for an Ni-NTA affinity chromatography assay that may be utilized to uncover insightful information about the nature of protein-protein interactions during iron-sulfur (Fe-S) cluster biogenesis reactions.

Neurosurgical Skills Assessment: Measuring Technical Proficiency in Neurosurgery Residents Through Intraoperative Video Evaluations.

OBJECTIVES: Although technical skills are fundamental in neurosurgery, there is little agreement on how to describe, measure, or compare skills among surgeons. The primary goal of this study was to develop a quantitative grading scale for technical surgical performance that distinguishes operator skill when graded by domain experts (residents, attendings, and nonsurgeons). Scores provided by raters should be highly reliable with respect to scores from other observers. METHODS: Neurosurgery residents were fitted with a head-mounted video camera while performing craniotomies under attending supervision. Seven videos, 1 from each postgraduate year (PGY) level (1-7), were anonymized and scored by 16 attendings, 8 residents, and 7 nonsurgeons using a grading scale. Seven skills were graded: incision, efficiency of instrument use, cauterization, tissue handling, drilling/craniotomy, confidence, and training level. RESULTS: A strong correlation was found between skills score and PGY year (P < 0.001, analysis of variance). Junior residents (PGY 1-3) had significantly lower scores than did senior residents (PGY 4-7, P < 0.001, t test). Significant variation among junior residents was observed, and senior residents' scores were not significantly different from one another. Interrater reliability, measured against other observers, was high (r = 0.581 ± 0.245, Spearman), as was assessment of resident training level (r = 0.583 ± 0.278, Spearman). Both variables were strongly correlated (r = 0.90, Pearson). Attendings, residents, and nonsurgeons did not score differently (P = 0.46, analysis of variance). CONCLUSIONS: Technical skills of neurosurgery residents recorded during craniotomy can be measured with high interrater reliability. Surgeons and nonsurgeons alike readily distinguish different skill levels. This type of assessment could be used to coach residents, to track performance over time, and potentially to compare skill levels. Developing an objective tool to evaluate surgical performance would be useful in several areas of neurosurgery education.

Regional gray matter atrophy in relapsing remitting multiple sclerosis: baseline analysis of multi-center data.

Regional gray matter (GM) atrophy in multiple sclerosis (MS) at disease onset and its temporal variation can provide objective information regarding disease evolution. An automated pipeline for estimating atrophy of various GM structures was developed using tensor based morphometry (TBM) and implemented on a multi-center sub-cohort of 1008 relapsing remitting MS (RRMS) patients enrolled in a Phase 3 clinical trial. Four hundred age and gender matched healthy controls were used for comparison. Using the analysis of covariance, atrophy differences between MS patients and healthy controls were assessed on a voxel-by-voxel analysis. Regional GM atrophy was observed in a number of deep GM structures that included thalamus, caudate nucleus, putamen, and cortical GM regions. General linear regression analysis was performed to analyze the effects of age, gender, and scanner field strength, and imaging sequence on the regional atrophy. Correlations between regional GM volumes and expanded disability status scale (EDSS) scores, disease duration (DD), T2 lesion load (T2 LL), T1 lesion load (T1 LL), and normalized cerebrospinal fluid (nCSF) were analyzed using Pearson׳s correlation coefficient. Thalamic atrophy observed in MS patients compared to healthy controls remained consistent within subgroups based on gender and scanner field strength. Weak correlations between thalamic volume and EDSS (r=-0.133; p<0.001) and DD (r=-0.098; p=0.003) were observed. Of all the structures, thalamic volume moderately correlated with T2 LL (r=-0.492; P-value<0.001), T1 LL (r=-0.473; P-value<0.001) and nCSF (r=-0.367; P-value<0.001).

Smoking is not associated with autoantibody production in systemic lupus erythematosus patients, unaffected first-degree relatives, nor healthy controls.

OBJECTIVE: The objective of this paper is to examine whether smoking is associated with autoantibody production in systemic lupus erythematosus (SLE) patients, unaffected first-degree relatives (FDR) of individuals with SLE--a group at increased risk of developing SLE--or unaffected, unrelated controls. METHODS: Detailed demographic, environmental, clinical, and therapeutic information was collected by questionnaire on 1242 SLE patients, 981 FDRs, and 946 controls in the Lupus Family Registry and Repository; a blood sample was obtained. All sera were tested for multiple lupus autoantibodies by immunofluorescence and luminex bead-based assays. Generalized estimating equations, adjusting for age, gender, and ethnicity and accounting for correlation within families, were used to assess smoking status with the dichotomous outcome variables of positivity for SLE status, positivity of ANA by immunofluorescence (≥1:120), positivity for ≥1 autoantibody by the luminex assay, and positivity for each of the 11 autoantibodies. RESULTS: Current smoking was associated with being positive for ≥1 autoantibody (excluding ANA) (adjusted OR = 1.53, 95% CI 1.04-2.24) in our subjects with SLE. No association was observed in unaffected FDRs or healthy controls. Former smoking was associated with anti-Ro/SS-A60 in our unaffected FDRs. There was an increased association with anti-nRNP A seropositivity, as well as a decreased association with anti-nRNP 68 positivity, in current smokers in SLE subjects. CONCLUSIONS: No clear association between smoking status and individual autoantibodies was detected in SLE patients, unaffected FDRs, nor healthy controls within this collection. The association of smoking with SLE may therefore manifest its risk through mechanisms outside of autoantibody production, at least for the specificities tested.

Serial atlas-based diffusion tensor imaging study of uncomplicated mild traumatic brain injury in adults.

Abstract In this report, we applied diffusion tensor imaging (DTI) methods in 36 patients with uncomplicated mild traumatic brain injury (mTBI) and a comparison group of 37 participants with orthopedic injury. Our aim was to characterize regional and global macro- and microstructural attributes of white matter (WM), gray matter (GM), in addition to volume and diffusivity of cerebrospinal fluid (CSF) to identify and differentiate patterns of acute and short-term recovery. Given that previous DTI reports on mTBI in adults using a region-of-interest approach implicated the corona radiata (CR), corpus callosum, and hippocampus, we analyzed and quantified DTI metrics of these regions using atlas-based methods. The normalized volume percentages of global CSF, GM, and WM were not different between the mTBI and orthopedic comparison (OC) groups at either the baseline or follow-up time points or between the baseline and follow-up time points within the OC group (p>0.17; uncorrected for multiple comparisons). The DTI metrics did not differ between groups at either occasion. However, an increase was noted on follow-up in the OC group in the global mean diffusivity of GM (uncorrected p=0.003) and WM (uncorrected p=0.02), indicating a decrease in diffusivity at the 3-month postinjury, as compared to the baseline scan. An analysis of the DTI data collected longitudinally in the CR show insignificant changes in the OC group (p>0.08; N=37). CR radial diffusivity was found to be elevated in the between-group comparison at baseline (mTBI1 vs. OC1), but did not differ in the within-group comparison (mTBI1 vs. mTBI2; N=19), suggesting the possible resolution of edema. Our analysis of the cross-sectional and follow-up data, which is uncorrected for multiple comparisons, demonstrates dissociation between volumetric (macrostructural) and tissue integrity (microstructural) attributes and shows the potential utility of DTI to capture transient edema in the CR.

The Oklahoma Thrombotic Thrombocytopenic Purpura-haemolytic Uraemic Syndrome Registry. A model for clinical research, education and patient care.

The Oklahoma Thrombotic Thrombocytopenic Purpura-Haemolytic Uraemic Syndrome (TTP-HUS) Registry has a 24 year record of success for collaborative clinical research, education, and patient care. This article tells the story of how the Registry began and it describes the Registry's structure and function. The Registry provides a model for using a cohort of consecutive patients to investigate a rare disorder. Collaboration between Oklahoma, United States and Bern, Switzerland has been the basis for successful interpretation of Registry data. Registry data have provided new insights into the evaluation and management of TTP. Because recovery from acute episodes of TTP has been assumed to be complete, the increased prevalence of hypertension, diabetes, depression, and death documented by long-term follow-up was unexpected. Registry data have provided opportunities for projects for students and trainees, education of physicians and nurses, and also for patients themselves. During our follow-up, patients have also educated Registry investigators about problems that persist after recovery from an acute episode of TTP. Most important, Registry data have resulted in important improvements for patient care.

The incidence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency.

BACKGROUND: Accurate estimates of the incidence of thrombotic thrombocytopenic purpura (TTP) are important to assess the resources required for current treatments as well as to anticipate the need to develop new treatments. Previous estimates have been indirect and have not reported data on patients with ADAMTS-13 deficiency. OBJECTIVE: To determine the incidence of patients with TTP-hemolytic uremic syndrome (HUS) in three categories: all patients with clinically suspected TTP-HUS, patients with idiopathic TTP-HUS, and patients with severe ADAMTS-13 deficiency. METHODS: Incidence rates were estimated from the Oklahoma TTP-HUS Registry, analyzing all 206 consecutive patients from January 1, 1996 to June 30, 2004 who were treated with plasma exchange for their initial episode of clinically suspected TTP-HUS. ADAMTS-13 activity was measured in 186 (90%) of the 206 patients. RESULTS: The age-sex-race standardized annual incidence rates were 11.29 x 10(6) (95% CI: 9.70-12.88) for all patients with clinically suspected TTP-HUS; 4.46 x 10(6) (95% CI: 3.43-5.50) for patients with idiopathic TTP-HUS; and 1.74 x 10(6) (95% CI: 1.06-2.41) for patients with severe ADAMTS-13 deficiency (<5% activity). In all three categories, the incidence rates were greater for women and for blacks. For patients with severe ADAMTS-13 deficiency, the age-sex standardized incidence rate ratio of blacks to non-blacks was 9.29 (95% CI: 4.33-19.93). CONCLUSIONS: Accurate incidence rate estimates for all patients with clinically suspected TTP-HUS, idiopathic TTP-HUS, and TTP associated with severe ADAMTS-13 deficiency have been determined. The greater incidence among women and blacks is comparable with their increased risk for other autoimmune disorders.

Factors influencing the publishing efforts of graduate students in nursing.

The purposes of this study were to identify factors influencing publication efforts of graduate students in nursing and determine the extent to which graduate students' scholarly activities contribute to the creation and dissemination of knowledge in nursing, as evidenced by publication in a professional journal. Authors of articles in Nursing Research were surveyed to assess their status as graduate students during the conceptualization, development, and publication of nursing research studies. The sample consisted of 633 authors of manuscripts published in Nursing Research from 1987 to 1991. The study design was descriptive. A survey questionnaire elicited data on graduate student status and factors that influenced the initiation and completion of the project. The data were analyzed using descriptive statistical techniques. The results of the study suggest that graduate students in nursing make important contributions to the advancement and dissemination of nursing knowledge. Factors that influence graduate students to engage in the process include academic requirements (e.g., thesis, dissertation, coursework), faculty involvement and support, and the ability to self-select the research topic.

Where do Americans live abroad?

"This article examines the factors that influence emigration of U.S. citizens. Data from a 1993 survey administered by the U.S. Department of State as part of an evacuation requirements report form the basis for the empirical analysis. The empirical analysis explains the distribution of U.S. citizens residing in 65 foreign countries in terms of economic and political characteristics of the foreign states. The study finds that U.S. citizens are more likely to reside in rich and close countries than in distant and poor countries and that the foreign country's ties to the U.S. immigrant population and the use of the English language are important determinants of where Americans settle abroad. Political conditions and U.S. military presence also influence the choice of foreign residence."

Interactive influences of ethnicity, gender and parental hypertension on hemodynamic responses to behavioral challenge.

To determine the independent and interactive influences of ethnicity, gender and parental hypertension on the magnitude and patterning of hemodynamic responses to standardized laboratory stressors, 112 normotensive, young adult African-American and Caucasian subjects (56 women, 56 men) completed a four-task protocol: three psychological stressors (the Stroop Color Word task, mental arithmetic and mirror tracing) and the forehead cold pressor test. Blood pressure (BP), heart rate (HR) and impedance derived measures of cardiac pre-ejection period and stroke volume were measured at rest and during each task; calculated indices of cardiac output and total peripheral resistance were also computed. Women responded to the psychological stressors with significantly larger increases in HR and cardiac output, less change in total peripheral resistance and greater attenuation of cardiac pre-ejection period than did men; however, blood pressure responses did not vary by gender, ethnicity or parental history of hypertension. Across tasks, African Americans showed larger elevations in total peripheral resistance than did Caucasians; conversely Caucasian subjects showed a more pronounced cardiac responsivity to stress, as evidenced by an elevated cardiac output and concomitant decrease in cardiac pre-ejection period, compared to their African-American counterparts. The ethnic differences in reactivity to psychological stressors were more apparent among males, while the gender differences were generally more pronounced among African Americans. Finally, the cold pressor test elicited larger increases in systolic blood pressure (SBP) among Caucasian subjects with family history positive (FH+), relative to family history negative (FH-) subjects, and also caused a greater reduction in HR among males compared to females.

The role of socioeconomic status and serum fatty acids in the relationship between intake of animal foods and cardiovascular risk factors.

Little is known regarding the relationship of serum fatty acids to cardiovascular risk factors in Nigerian populations. Civil servants with higher socioeconomic status (SES) in Nigeria appear to be in cultural transition toward a more Westernized lifestyle. For this study the food intakes of 397 civil servants were estimated from two 24-h recalls. Fatty acids in serum total lipids were measured in both absolute weight concentration and percentage composition. Daily meat intake was 43.5 g, and fish intake was 70.5 g. The intakes of meat, eggs, and milk were higher in high SES Nigerians than in low SES Nigerians. The concentration of total fatty acids (TFA, the sum of 12 serum fatty acids) was also higher in high SES men and women, as compared with low SES men and women (2064, 2060, 1831, and 1776 mg/L, respectively). There were significant direct associations between meat intake and serum level of arachidonic acid, and between fish intake and serum levels of eicosapentaenoic acid and docosahexaenoic acid. TFA was positively associated with cholesterol, low-density-lipoprotein cholesterol (LDLc), and triglycerides across gender and SES groups after adjustment for body mass index, fasting insulin level, and age. Nigerian women were compared with two groups of American women. We concluded that fatty acids in absolute weight concentration reflected the amount of fat intake. The level of TFA was directly related to cardiovascular risk factors in Nigerians. Follow-up of such populations in cultural transition can facilitate the understanding of the true roles of animal food intake in the early evolution of atherosclerosis.

Absence of enhanced sympathoadrenal activity and behaviorally evoked cardiovascular reactivity among offspring of hypertensives.

To determine whether offspring of hypertensives show enhanced sympathetic nervous system activity, we evaluated several indices of sympathoadrenal activation and cardiovascular responsiveness to behavioral stimuli among 90 normotensive, young adult men having either one or two hypertensive parents (PH+(-), PH++) or normotensive parents only (PH--) (n = 30/group). Measurements included heart rate (HR) and blood pressure (BP) reactions to three mental stressors (the Stroop test, mental arithmetic, mirror tracing), a cold pressor test, postural adjustment (60 degrees upright tilt), isometric exercise and bicycle ergometry, as well as the 24-h excretion of catecholamines (epinephrine [E], norepinephrine [NE]) and venous plasma catecholamine concentrations, both at rest (seated and supine) and in response to the Stroop test and upright tilt. The three groups did not differ in age, education, body mass index (BMI), estimated aerobic fitness, resting HR, cardiac preejection period (PEP) and PEP:LVET (left ventricular ejection time) ratio, 24-h Na or K excretion, or fasting lipids, insulin or plasma renin activity. Resting systolic and diastolic BP varied as a function of parental hypertension, and were significantly higher in PH++ than among PH-- subjects (P < .05). No significant group difference was observed on any measure of plasma or urinary catecholamines, nor did offspring of hypertensives (PH++ or PH+-) showed greater HR or BP reactions than PH-- subjects to any of the several laboratory challenges. In sum, we find no evidence of enhanced sympathetic activity or heightened cardiovascular responsiveness among normotensive young adults who are familially predisposed to essential hypertension.

Resiliency characteristics and Rorschach variables in children and adolescents with severe burns.

Three raters classified 40 children and adolescents (ages 8 to 19 years) with severe burns who were placed in two groups designated as Resilient (N = 28) and Nonresilient (N = 12). Nine hypothesized differences in Rorschach responding between groups were developed through a review of the literature and operationalized through descriptive statements from a rating scale now being developed. The Resilient group gave more Cooperative Movement responses than the Nonresilient group (p = 0.0270), and they were more likely to have D scores that were within the normal range (p = 0.0700). The Nonresilient group had lower Egocentricity Index scores than the Resilient group (p = 0.0368) and more often had a positive Coping Deficit Index (p = 0.1285). Texture, Diffuse Shading, and Passive: Active responses appeared similar between groups. Differences found concerning Experience Actual and Z frequency were not statistically significant. Possible interventions addressing the emotional needs of burned children and adolescents such as strengthening certain personality characteristics are noted.

Utility of the National Death Index for ascertainment of mortality among cancer prevention study II participants.

This paper reports the results of testing and using the National Death Index to ascertain vital status in the American Cancer Society's prospective cohort study, Cancer Prevention Study II. This cohort of over one million men and women, enrolled by volunteers in 1982, is one of the largest ever to be linked with the National Death Index. In a linkage of over 15,000 persons whose vital status through 1988 had been traced through manual follow-up, 93% of all known deaths were ascertained. Sensitivity varied by demographic factors (race, sex) and availability of identifying information (Social Security number, middle initial). When the Social Security number was available, 97% of known deaths were accurately identified. A computerized matching algorithm was used to minimize manual review of records. With this method, the authors were able efficiently and accurately to reject the many false-positive matches while maintaining a reasonable level of manual record review and death certificate acquisition, thus allowing for continued automated follow-up of this valuable cohort.

Family history studies in hypertension research. Review of the literature.

Reviewed in the present article are over 150 family history studies of essential hypertension. By comparing normotensive individuals with and without a family history of hypertension, these investigations seek to identify potential pathophysiologic factors that predate the development of high blood pressure. The research literatures summarized here represent four general areas: 1) cellular salt transport mechanisms, 2) dietary sodium, intravascular volume, and renal function, 3) cardiovascular morphology and physiology, and 4) cardiovascular reactivity. There is strong evidence of early cardiac morphologic changes (greater left ventricular wall thickness and mass) and altered peripheral vascular capacity and responsivity to pressor stimuli among normotensive individuals with a positive family history. In contrast, cardiac output, sodium consumption, intravascular volume, and cardiovascular responses to isometric exercise and standing do not differ in persons with and without a family history of hypertension. Other articles are characterized by inconsistent results, which may be a reflection of the heterogeneity of essential hypertension, but also may be due to methodological weaknesses. The latter include failure to confirm the blood pressure status of ostensibly hypertensive or normotensive family members and the use of relatively weak study designs (eg, where a positive history is defined by a single, hypertensive first-degree relative).

Number-related discrimination and summation by squirrel monkeys (Saimiri sciureus sciureus and S. boliviensus boliviensus) on the basis of the number of sides of polygons.

In Experiment 1, with the number of sides or angles of irregular polygons as cues, programmed training, and a 90% correct criterion (36 of 40), 2 squirrel monkeys' (Saimiri sciureus sciureus and S. boliviensus boliviensus) best performances were to discriminate heptagons from octagons, a 3rd's best was hexagons from heptagons, and a 4th's best was pentagons from heptagons. In Experiment 2, on most trials 2 polygons on one or both discriminanda had to be summed to determine which discrimination had the total fewer sides. Only 1 monkey met criterion (27 of 30) on the 2 tasks, 6 vs. 8 and 7 vs. 8 sides, but the other 3 performed better than chance on the 6 vs. 8 task. We conclude that previous studies of animals' discrimination of polygons in terms of complexity were minimally relevant to this work, and counting and subitizing were rejected in favor of a prototype-matching process to explain our monkeys' performances.

A rational approach to the use of hormonal replacement therapy in postmenopausal and older women.

This report reviews the use of hormonal therapy in postmenopausal women and gives specific attention to its benefits in the older patients. Concomitant use of progestin is recommended for all but the very old who are being treated for urogenital problems. Strategies for minimizing withdrawal bleeding and the adverse impacts of progestins on lipoprotein subfractions are discussed.