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Background: Hypertension has been linked to socially patterned stressors, including discrimination. Few studies have quantified the risk of hypertension associated with exposure to perceived job discrimination. Methods: We used prospective cohort data from the Sister Study (enrollment from 2003–2009) to estimate self‐reported incident hypertension associated with perceived job discrimination based on race, gender, age, sexual orientation, or health status. Job discrimination in the prior 5 years was assessed in 2008–2012, and incident doctor‐diagnosed hypertension was ascertained in previously hypertension‐free participants. Results: Among the 16,770 eligible participants aged 37–78 years at the start of follow‐up, 10.5% reported job discrimination in the past 5 years, and 19.2% (n = 3226) reported incident hypertension during a median follow‐up of 9.7 years (interquartile range 8.2–11.0 years). Self‐reported poor health or inclusion in minoritized groups based on race/ethnicity or sexual orientation were more frequent among those reporting job discrimination. In a Cox proportional hazards model adjusting for covariates, report of at least one type of job discrimination (compared to none) was associated with a 14% (hazard ratio = 1.14 [95% confidence: 1.02–1.27]) higher hypertension risk. Results from sensitivity analyses reinforced the findings. Conclusions: Results suggest that interventions addressing job discrimination could have workplace equity and health benefits. [ABSTRACT FROM AUTHOR]

Background: Attention deficit/hyperactivity disorder (ADHD) is associated with emotional problems, and their co‐occurrence often leads to worse outcomes. We investigated the developmental associations between ADHD and emotional problems from childhood to early adolescence and examined the genetic and environmental contributions to their developmental link. We further tested whether this developmental association remained across the transition to young adulthood. Methods: We used data from the Environmental Risk (E‐Risk) Longitudinal Twin Study, a cohort of 2,232 British twins. In childhood, ADHD and emotional problems were assessed at ages 5, 7, 10 and 12 with mothers' and teachers' reports. At age 18, we used self‐reported symptoms according to DSM‐5 criteria for ADHD, and DSM‐IV for anxiety and depression. Results: Longitudinal analyses showed that earlier ADHD was associated with later emotional problems consistently across childhood. However, earlier emotional problems were not associated with later ADHD symptoms. The developmental association between ADHD and later emotional problems in childhood was entirely explained by common genetic factors. Consistent with results in childhood, earlier symptoms of ADHD were associated with later emotional problems during the transition to young adulthood. Conclusions: Our findings demonstrate that ADHD symptoms are predictors of the development of emotional problems, from childhood up to young adulthood, through shared genetic influences. Interventions targeting ADHD symptoms might prevent the development of emotional problems. Clinicians treating youth with ADHD must be aware of their risk for developing emotional problems and ought to assess, monitor and treat emotional problems alongside ADHD symptoms from childhood to adulthood. [ABSTRACT FROM AUTHOR]

This study tested implications of new genetic discoveries for understanding the association between parental investment and children's educational attainment. A novel design matched genetic data from 860 British mothers and their children with home-visit measures of parenting: the E-Risk Study. Three findings emerged. First, both mothers' and children's education-associated genetics, summarized in a genome-wide polygenic score, were associated with parenting-a gene-environment correlation. Second, accounting for genetic influences slightly reduced associations between parenting and children's attainment-indicating some genetic confounding. Third, mothers' genetics were associated with children's attainment over and above children's own genetics, via cognitively stimulating parenting-an environmentally mediated effect. Findings imply that, when interpreting parents' effects on children, environmentalists must consider genetic transmission, but geneticists must also consider environmental transmission. [ABSTRACT FROM AUTHOR]

The aim of this study was to disentangle pervasive from situational antisocial behaviors using multiple informants, and to investigate their genetic and environmental etiologies in preadolescence and across time. Antisocial behaviors were assessed in 2,232 twins from the Environmental Risk (E-Risk) Longitudinal Twin Study at ages 5 and 12. Pervasive antisocial behaviors were defined as behaviors that mothers, teachers, interviewers, and twins themselves agreed on. Results from a psychometric model indicated that the variation in children's pervasive antisocial behaviors was mostly accounted for by familial influences that originated in childhood, whereas situational behaviors were explained by newly emerging nonshared environmental and genetic influences. This study shows that children's pervasive and situational antisocial behaviors have distinct etiologies that could guide research and treatment. [ABSTRACT FROM AUTHOR]

Background Children with externalising problems are at risk of developing internalising problems as they grow older. The pathways underlying this developmental association remain to be elucidated. We tested two processes that could explain why some children with externalising problems develop internalising symptoms in preadolescence: a mediation model whereby the association between early externalising and later new internalising symptoms is explained by negative experiences; and a genetic model, whereby genes influence both problems. Methods We used data from the Environmental Risk (E-Risk) Study, a 1994-1995 birth cohort of 2,232 twins born in England and Wales. We assessed externalising and internalising problems using combined mothers' and teachers' ratings at age 5 and 12. We measured bullying victimisation, maternal dissatisfaction and academic difficulties between age 7 and 10 and used linear regression analyses to test the effects of these negative experiences on the association between early externalising and later internalising problems. We employed a Cholesky decomposition to examine the genetic influences on the association. Results Children with externalising problems at age 5 showed increased rates of new internalising problems at age 12 ( r = .24, p < .001). Negative experiences accounted for some of the association between early externalising and later internalising problems. Behavioural-genetic analyses indicated that genes influencing early externalising problems also affected later internalising problems. Conclusions Our findings highlight the role of genetic influences in explaining why some children with externalising problems develop internalising symptoms in preadolescence. Negative experiences also contribute to the association, possibly through gene-environment interplay. Mental health professionals should monitor the development of internalising symptoms in young children with externalising problems. [ABSTRACT FROM AUTHOR]

R2781 --> 761.15 --> Hypobaric hypoxia (HH) experienced at high altitude initiates a series of physiological adaptations to maintain homeostasis. One such adaptation is the activation of the Epo gene which encodes the glycoprotein hormone erythropoietin (EPO). Increased circulating EPO levels defend against HH by facilitating blood O2 transport through increasing red blood cell production. HH also increases blood pressure (BP) through activation of the sympathetic nervous system and the ensuing elevation of circulating catecholamine levels. The present study examined the role of sympathetic nerve activation in HH‐evoked Epo gene activation and elevated circulating levels of EPO. Studies were performed on adult, male wild‐type (WT) mice treated with 18 hours of HH (0.4 atmospheres), simulating low O2 condition experienced at high altitude. Our results showed increased renal Epo gene abundance and elevated plasma EPO levels. Remarkably, these responses were either markedly attenuated or absent in mice with selective ablation of adrenal medulla as well as after treatment with propranolol, a non‐selective beta‐adrenergic receptor blocker. Moreover, infusion of epinephrine alone activated renal Epo gene and elevated plasma EPO levels. These results suggest that sympathetic nerve activation and the ensuing increase in plasma epinephrine contribute to Epo gene activation by HH. [ABSTRACT FROM AUTHOR]

Disposable technology is being used more each year in the biotechnology industry. Disposable bioreactors allow one to avoid expenses associated with cleaning, assembly and operations, as well as equipment validation. The WAVE bioreactor is well established for Chinese Hamster Ovary (CHO) production, however, it has not yet been thoroughly tested for E. coli production because of the high oxygen demand and temperature maintenance requirements of that platform. The objective of this study is to establish a robust process to generate inoculum for E. coli production fermentations in a WAVE bioreactor. We opted not to evaluate the WAVE system for production cultures because of the high cell densities required in our current E. coli production processes. Instead, the WAVE bioreactor 20/50 system was evaluated at laboratory scale (10-L) to generate inoculum with target optical densities (OD550) of 15 within 7–9 h (pre-established target for stainless steel fermentors). The maximum settings for rock rate (40 rpm) and angle (10.5) were used to maximize mass transfer. The gas feed was also supplemented with additional oxygen to meet the high respiratory demand of the culture. The results showed that the growth profiles for the inoculum cultures were similar to those obtained from conventional stainless steel fermentors. These inoculum cultures were subsequently inoculated into 10-L working volume stainless steel fermentors to evaluate the inocula performance of two different production systems during recombinant protein production. The results of these production cultures using WAVE inocula showed that the growth and recombinant protein production was comparable to the control data set. Furthermore, an economic analysis showed that the WAVE system would require less capital investment for installation and operating expenses would be less than traditional stainless steel systems. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [ABSTRACT FROM AUTHOR]

As part of an investigation to identify potential new viral reduction strategies, ultraviolet-C (UV-C) light was examined. Although this technology has been known for decades to possess excellent virus inactivation capabilities, UV-C light can also introduce significant unwanted damage to proteins. To study the effect on monoclonal antibodies, three different antibodies were subjected to varying levels of UV-C light using a novel dosing device from Bayer Technology Services GmbH. The range of fluencies (or doses) covered was between 0 and 300 J/m2 at a wavelength of 254 nm. Product quality data generated from the processed pools showed only minimal damage done to the antibodies. Aggregate formation was low for two of the three antibodies tested. Acidic and basic variants increased for all three antibodies, with the basic species increasing more than the acidic species. Peptide maps made for the three sets of pools showed no damage to two of the three antibody backbones, whereas the third antibody had very low levels of methionine oxidation evident. Samples held at 2-8°C for 33 days showed no increase in aggregates or charge variants, indicating that the proteins did not degrade and were not damaged further by reactive or catalytic species that may have been created on exposure to UV-C light. Overall, UV-C light was shown to induce very little damage to monoclonal antibodies at lower fluencies and appears to be a viable option for viral inactivation in biotechnology applications. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [ABSTRACT FROM AUTHOR]

A series of short chain fatty acid derivatives of aminimides were shown to possess hypolipidemic activity in rats and mice. Most of the agents tested lowered both serum cholesterol and triglyceride levels by at least 30% in mice and were effective in hyperlipidemic induced mice. 1,1-Dimethyl-1-(2-hydroxypropyl)-amine mersitimide lowered serum cholesterol levels 41% and serum triglyceride levels 56% at 20 mg/kg/day I.P. after 16 days. The same agent was active orally when administered to rats with a 38% reduction in serum cholesterol and a 52% reduction in serum triglycerides after 14 days. The agents inhibited liver acetyl CoA synthetase, ATP dependent citrate lyase and phosphatidate phosphohydrolase activities in vitro and in vivo. Reduction of cholesterol, triglycerides, neutral lipids and phospholipid levels were noted in the livers of mice treated for 16 days. In rat studies, cholesterol, triglyceride and phospholipid levels were reduced in liver, small intestine and the feces after two weeks' dosing. The cholesterol content was reduced in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions but elevated in the high density lipoproteins (HDL). Triglyceride levels were lowered in the VLDL, and neutral lipid levels were reduced in the chylomicron and VLDL fractions. [ABSTRACT FROM AUTHOR]

Background Mounting evidence has demonstrated a role of psychosocial stressors such as discrimination in hypertension and cardiovascular diseases. The objective of this study was to provide the first instance of research evidence examining prospective associations of workplace discrimination with onset of hypertension. Methods and Results Data were from MIDUS (Midlife in the United States), a prospective cohort study of adults in the United States. Baseline data were collected in 2004 to 2006, with an average 8-year follow-up period. Workers with self-reported hypertension at baseline were excluded, yielding a sample size of 1246 participants for the main analysis. Workplace discrimination was assessed using a validated 6-item instrument. During follow-up with 9923.17 person-years, 319 workers reported onset of hypertension, and incidence rates of hypertension were 25.90, 30.84, and 39.33 per 1000 person-years among participants with low, intermediate, and high levels of workplace discrimination, respectively. Cox proportional hazards regression analyses demonstrated that workers who experienced high exposure to workplace discrimination, compared with workers with low exposure, had a higher hazard of hypertension (adjusted hazard ratio, 1.54 [95% CI, 1.11-2.13]). Sensitivity analysis excluding more baseline hypertension cases based on additional information on blood pressure plus antihypertensive medication use (N=975) showed slightly stronger associations. A trend analysis showed an exposure-response association. Conclusions Workplace discrimination was prospectively associated with elevated risk of hypertension among US workers. The adverse impacts of discrimination on cardiovascular disease have major implications for workers' health and indicate a need for government and employer policy interventions addressing discrimination.