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Routine Bovine Viral Diarrhoea Virus (BVDV) monitoring of a commercial beef herd in southern New South Wales over a 10‐year period provided an opportunity to assess the impact of the introduction of BVDV on that herd. BVDV antibody testing provided strong evidence that the herd was initially free of BVDV (2009–2011). Testing from 2012 suggested BVDV had been introduced into the herd and this was confirmed in 2015 with the identification of persistently infected (PI) animals. Having become established in the herd, the owners then set out to eliminate BVDV from the herd. Antigen testing aimed at identifying PI animals revealed BVDV was already absent from the herd. Subsequent antibody testing confirmed that the herd was now free from BVDV. Despite the incursion of BVDV in this herd, there was little measurable impact on reproductive performance (pregnancy rates), although suspected increased calf losses from birth to calf marking were reported. This is the first time such self‐clearance has been documented as part of a longitudinal study under Australian conditions. [ABSTRACT FROM AUTHOR]

Bovine viral diarrhoea virus (BVDV) is an economically significant disease affecting the Australian cattle industry, with losses stemming from decreased production and reproductive performance and control costs. However, these losses can be difficult to appreciate, particularly in endemic regions. Overall, there is a variable but high herd‐level seroprevalence in Australia. Despite a potentially high financial burden of the disease, the onus for control ultimately falls on producers and strategies employed will vary between regions. A cross‐sectional study, using a postal survey, was conducted in 2013 to evaluate the BVDV knowledge, attitudes and management practices utilised by Australian cattle producers. A total of 192 producers participated in the study, and results indicate that knowledge and attitudes towards disease risk are variable and can be improved. Producer knowledge of how persistently infected (PI) animals are produced was higher than that of disease outcomes or transmission pathways. Implementation of biosecurity practices was limited, with approximately half of respondents employing quarantine procedures for introduced stock and only 2% indicating they would antigen test introduced stock for BVDV. Approximately a third (36%) of producers reported engaging in BVDV control, with the majority of these using vaccination strategies over deliberate exposure to a PI. Knowledge of and engagement with BVDV control was positively influenced by the producer relationships with veterinarians. Findings from this study suggest that building on education and delivering a consistent message among stakeholders would likely improve producer awareness and understanding in relation to BVDV and support decision making in BVDV management. [ABSTRACT FROM AUTHOR]

Problem: In pregnancy, lower socioeconomic status (SES) is associated with adverse outcomes, which is partly attributed to chronic inflammation. Our study compared the maternal serum cytokine profiles in patients with low and high SES., Method of Study: This retrospective cohort study compared maternal serum cytokine profiles between Medicaid-insured patients who delivered at an urban safety-net hospital (low SES) and privately-insured patients who delivered at a community-based academic hospital (high SES) in Atlanta, GA (n = 32-33/group). Serum samples were obtained during prenatal venipuncture from 13 to 38 weeks' gestation and the cohorts were matched by gestational age. Interferon (IFN)-γ, Interleukin (IL)-10, IL-1β, IL-4, IL-6, IL-8, and Tumor Necrosis Factor (TNF)-α were assayed from maternal serum samples using a standard ELISA assay., Results: Median concentrations of IL-6, a promotor of chronic inflammation, were higher in the low SES group (0.85 vs. 0.49 pg/mL, p < .001), while median levels of IL-1β, a potent monocyte activator, and TNF-α, a master regulator of acute inflammation, were lower in the low SES group (0.09 vs. 0.46 pg/mL, p < .001, and 1.23 vs. 1.58 pg/mL, p = .002, respectively) as compared to the high SES group. After adjusting for maternal age, obesity, hypertensive disorders, and gestational age at delivery, the differences in IL-6 and IL-1β by SES persisted (p = .0002 and p < .0001, respectively)., Conclusions: In this retrospective cohort study, there were significant differences in levels of pro-inflammatory cytokines during pregnancy for groups defined by SES, even after adjustment for confounding variables. Our data are foundational for further research to investigate SES-associated inflammation that may contribute to adverse pregnancy outcomes., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: The developmental origins of health and disease (DOHaD) hypothesis describes how early childhood stress affects morbidity and mortality later in life. The role of early childhood stress in mortality from infectious disease is understudied. Stressors in early childhood that weaken the immune system may result in increased susceptibility to infectious disease in adulthood. Weaning is one of the earliest potential periods of significant stress in early childhood. This research investigates the effect of weaning after ~6 months of age on cholera mortality among 18th-19th-century Italian populations by determining if earlier breastfeeding cessation is associated with earlier mortality, analyzing childhood dietary variation and physiological stress markers, and determining if age-at-weaning completion differs between catastrophic and attritional populations., Methods: Serial dentin stable carbon and nitrogen isotope analyses from canines are compared between catastrophic (n = 45) and attritional groups (n = 23). Canines are sectioned serially from crown to apex, and the increment's δ 15 N and δ 13 C are used to estimate age-at-weaning completion., Results: Catastrophic and attritional groups exhibit similar age-at-weaning completion (~2.8 years). Seventy-four percent of individuals lack elevated δ 15 N values in dentin that formed during infancy., Conclusions: Age-at-weaning completion was not a predisposing factor in cholera mortality in adulthood in this sample. Age-at-weaning completion may not be significantly associated with infectious disease mortality because weaning completion likely occurred after infants had adapted to consuming contaminated weanling foods. Individuals without detectable weaning curves may represent infants who received supplementary foods since birth or were weaned before the age of 6-9 months., (© 2023 Wiley Periodicals LLC.)

Background Durable memory decline may occur in older adults after surgical (coronary artery bypass grafting [CABG]) or nonsurgical (percutaneous coronary intervention) coronary revascularization. However, it is unknown whether individual memory risk can be predicted. We reanalyzed an epidemiological cohort of older adults to predict memory decline at ≈1 year after revascularization. Methods and Results We studied Health and Retirement Study participants who underwent CABG or percutaneous coronary intervention at age ≥65 years between 1998 and 2015 and participated in ≥1 biennial postprocedure assessment. Using a memory score based on direct and proxy cognitive tests, we identified participants whose actual postprocedure memory score was 1-2 ("mild") or >2 ("major") SDs below expected postprocedure performance. We modeled probability of memory decline using logistic regression on preoperatively known factors and evaluated model discrimination and calibration. A total of 1390 participants (551 CABG, 839 percutaneous coronary intervention) underwent CABG/percutaneous coronary intervention at 75±6 years old; 40% were women. The cohort was 83% non-Hispanic White, 8.4% non-Hispanic Black, 6.4% Hispanic ethnicity, and 1.7% from other groups masked by the HRS (Health and Retirement Study) to preserve participant confidentiality. At a median of 1.1 (interquartile range, 0.6-1.6) years after procedure, 267 (19%) had mild memory decline and 88 (6.3%) had major memory decline. Factors predicting memory decline included older age, frailty, and off-pump CABG; obesity was protective. The optimism-corrected area under the receiver operator characteristic curve was 0.73 (95% CI, 0.71-0.77). A cutoff of 50% probability of memory decline identified 14% of the cohort as high risk, and was 94% specific and 30% sensitive for late memory decline. Conclusions Preoperative factors can be used to predict late memory decline after coronary revascularization in an epidemiological cohort with high specificity.

Problem: Disruption in homeostatic feedback loops between inflammatory mediators and the hypothalamic-pituitary-adrenal (HPA) axis is a key mechanism linking chronic stress to inflammation and adverse health outcomes, including those occurring during pregnancy. In particular, alterations in glucocorticoid sensitivity may occur as a result of chronic stress, including that due to racial discrimination, and may be implicated in the persistent adverse maternal and infant health outcomes experienced by African Americans. While there are a few large-scale studies in human pregnancy that measure both cytokines and HPA axis hormones, to our knowledge, none directly measure glucocorticoid sensitivity at the cellular level, especially in an African American population., Method of Study: We measured the full range of the dexamethasone (DEX) dose-response suppression of TNF-α in first-trimester blood samples from 408 African American women and estimated leukocyte cell type contribution to the production of TNF-α., Results: The mean (SD) DEX level needed to inhibit TNF-α production by 50% (ie, DEX IC 50 ) was 9.8 (5.8) nmol/L. Monocytes appeared to be the main driver of Uninhibited TNF-α production, but monocyte counts explained only 14% of the variation. Monocyte counts were only weakly correlated with the DEX IC 50 (r = -.11, P < .05). Moreover, there was no statistically significant correlation between the DEX IC 50 and circulating pro-inflammatory (CRP, IL-6, IFN-γ) or anti-inflammatory (IL-10) mediators (P > .05)., Conclusion: These findings challenge some prior assumptions and position this comprehensive study of glucocorticoid sensitivity as an important anchor point in the growing recognition of interindividual variation in maternal HPA axis regulation and inflammatory responses., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Excessive alcohol use is extremely prevalent in the United States, particularly among trauma-exposed individuals. While several studies have examined genetic influences on alcohol use and related problems, this has not been studied in the context of trauma-exposed populations. We report results from a genome-wide association study of alcohol consumption and associated problems as measured by the alcohol use disorders identification test (AUDIT) in a trauma-exposed cohort. Results indicate a genome-wide significant association between total AUDIT score and rs1433375 [N = 1036, P = 2.61 × 10 -8 (dominant model), P = 7.76 × 10 -8 (additive model)], an intergenic single-nucleotide polymorphism located 323 kb upstream of the sodium channel and clathrin linker 1 (SCLT1) at 4q28. rs1433375 was also significant in a meta-analysis of two similar, but independent, cohorts (N = 1394, P = 0.0004), the Marine Resiliency Study and Systems Biology PTSD Biomarkers Consortium. Functional analysis indicated that rs1433375 was associated with SCLT1 gene expression and cortical-cerebellar functional connectivity measured via resting state functional magnetic resonance imaging. Together, findings suggest a role for sodium channel regulation and cerebellar functioning in alcohol use behavior. Identifying mechanisms underlying risk for problematic alcohol use in trauma-exposed populations is critical for future treatment and prevention efforts., (© 2017 Society for the Study of Addiction.)

Objective: Epigenetic modifications such as DNA methylation may play a key role in the aetiology and serve as biomarkers for post-traumatic stress disorder (PTSD). We performed a genomewide analysis to identify genes whose DNA methylation levels are associated with PTSD., Method: A total of 211 individuals comprising Australian male Vietnam War veterans (n = 96) and males from a general population belonging to the Grady Trauma Project (n = 115) were included. Genomewide DNA methylation was performed from peripheral blood using the Illumina arrays. Data analysis was performed using generalized linear regression models., Results: Differential DNA methylation of 17 previously reported PTSD candidate genes was associated with PTSD symptom severity. Genomewide analyses revealed CpG sites spanning BRSK1, LCN8, NFG and DOCK2 genes were associated with PTSD symptom severity. We replicated the findings of DOCK2 in an independent cohort. Pathway analysis revealed that among the associated genes, genes within actin cytoskeleton and focal adhesion molecular pathways were enriched., Conclusion: These data highlight the role of DNA methylation as biomarkers of PTSD. The results support the role of previous candidates and uncover novel genes associated with PTSD, such as DOCK2. This study contributes to our understanding of the biological underpinnings of PTSD., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Compelling evidence suggests that epigenetic mechanisms such as DNA methylation play a role in stress regulation and in the etiologic basis of stress related disorders such as Post traumatic Stress Disorder (PTSD). Here we describe the purpose and methods of an international consortium that was developed to study the role of epigenetics in PTSD. Inspired by the approach used in the Psychiatric Genomics Consortium, we brought together investigators representing seven cohorts with a collective sample size of N = 1147 that included detailed information on trauma exposure, PTSD symptoms, and genome-wide DNA methylation data. The objective of this consortium is to increase the analytical sample size by pooling data and combining expertise so that DNA methylation patterns associated with PTSD can be identified. Several quality control and analytical pipelines were evaluated for their control of genomic inflation and technical artifacts with a joint analysis procedure established to derive comparable data over the cohorts for meta-analysis. We propose methods to deal with ancestry population stratification and type I error inflation and discuss the advantages and disadvantages of applying robust error estimates. To evaluate our pipeline, we report results from an epigenome-wide association study (EWAS) of age, which is a well-characterized phenotype with known epigenetic associations. Overall, while EWAS are highly complex and subject to similar challenges as genome-wide association studies (GWAS), we demonstrate that an epigenetic meta-analysis with a relatively modest sample size can be well-powered to identify epigenetic associations. Our pipeline can be used as a framework for consortium efforts for EWAS., (© 2017 Wiley Periodicals, Inc.)

Genetic factors appear to be highly relevant to predicting differential risk for the development of post-traumatic stress disorder (PTSD). In a discovery sample, we conducted a genome-wide association study (GWAS) for PTSD using a small military cohort (Systems Biology PTSD Biomarkers Consortium; SBPBC, N = 147) that was designed as a case-controlled sample of highly exposed, recently returning veterans with and without combat-related PTSD. A genome-wide significant single nucleotide polymorphism (SNP), rs717947, at chromosome 4p15 (N = 147, β = 31.34, P = 1.28 × 10(-8) ) was found to associate with the gold-standard diagnostic measure for PTSD (the Clinician Administered PTSD Scale). We conducted replication and follow-up studies in an external sample, a larger urban community cohort (Grady Trauma Project, GTP, N = 2006), to determine the robustness and putative functionality of this risk variant. In the GTP replication sample, SNP rs717947 associated with PTSD diagnosis in females (N = 2006, P = 0.005), but not males. SNP rs717947 was also found to be a methylation quantitative trait locus (meQTL) in the GTP replication sample (N = 157, P = 0.002). Further, the risk allele of rs717947 was associated with decreased medial and dorsolateral cortical activation to fearful faces (N = 53, P < 0.05) in the GTP replication sample. These data identify a genome-wide significant polymorphism conferring risk for PTSD, which was associated with differential epigenetic regulation and with differential cortical responses to fear in a replication sample. These results may provide new insight into understanding genetic and epigenetic regulation of PTSD and intermediate phenotypes that contribute to this disorder., (© 2015 Wiley Periodicals, Inc.)

DNA methylation has become increasingly recognized in the etiology of psychiatric disorders. Because brain tissue is not accessible in living humans, epigenetic studies are most often conducted in blood. Saliva is often collected for genotyping studies but is rarely used to examine DNA methylation because the proportion of epithelial cells and leukocytes varies extensively between individuals. The goal of this study was to evaluate whether saliva DNA is informative for studies of psychiatric disorders. DNA methylation (HumanMethylation450 BeadChip) was assessed in saliva and blood samples from 64 adult African Americans. Analyses were conducted using linear regression adjusted for appropriate covariates, including estimated cellular proportions. DNA methylation from brain tissues (cerebellum, frontal cortex, entorhinal cortex, and superior temporal gyrus) was obtained from a publically available dataset. Saliva and blood methylation was clearly distinguishable though there was positive correlation overall. There was little correlation in CpG sites within relevant candidate genes. Correlated CpG sites were more likely to occur in areas of low CpG density (i.e., CpG shores and open seas). There was more variability in CpG sites from saliva than blood, which may reflect its heterogeneity. Finally, DNA methylation in saliva appeared more similar to patterns from each of the brain regions examined overall than methylation in blood. Thus, this study provides a framework for using DNA methylation from saliva and suggests that DNA methylation of saliva may offer distinct opportunities for epidemiological and longitudinal studies of psychiatric traits., (© 2014 Wiley Periodicals, Inc.)

A non-synonymous, single nucleotide polymorphism (SNP) in the gene coding for steroid 5-α-reductase type 2 (SRD5A2) is associated with reduced conversion of testosterone to dihydrotestosterone (DHT). Because SRD5A2 participates in the regulation of testosterone and cortisol metabolism, hormones shown to be dysregulated in patients with PTSD, we examined whether the V89L variant (rs523349) influences risk for post-traumatic stress disorder (PTSD). Study participants (N = 1,443) were traumatized African-American patients of low socioeconomic status with high rates of lifetime trauma exposure recruited from the primary care clinics of a large, urban hospital. PTSD symptoms were measured with the post-traumatic stress symptom scale (PSS). Subjects were genotyped for the V89L variant (rs523349) of SRD5A2. We initially found a significant sex-dependent effect of genotype in male but not female subjects on symptoms. Associations with PTSD symptoms were confirmed using a separate internal replication sample with identical methods of data analysis, followed by pooled analysis of the combined samples (N = 1,443, sex × genotype interaction P < 0.002; males: n = 536, P < 0.001). These data support the hypothesis that functional variation within SRD5A2 influences, in a sex-specific way, the severity of post-traumatic stress symptoms and risk for diagnosis of PTSD., (Copyright © 2013 Wiley Periodicals, Inc.)

Depression has been associated with reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. Genetic association studies of the BDNF Val66Met polymorphism (rs6265) in geriatric depression have produced inconsistent results. A meta-analysis of studies was conducted to compare the frequency of the BDNF Val66Met variant between cases with geriatric depression and age-matched controls. A total of five studies involving 523 cases with geriatric depression and 1,220 psychiatrically healthy controls was included. Met allele carriers had an increased risk for geriatric depression when compared to Val/Val homozygotes (P = 0.004, OR = 1.48, 95% CI = 1.13-1.93). Our findings suggest the BDNF Met allele may confer increased risk for depression as individual age., (Copyright © 2012 Wiley Periodicals, Inc.)

DNA methylation may mediate persistent changes in gene function following chronic stress. To examine this hypothesis, we evaluated African American subjects matched by age and sex, and stratified into four groups by post-traumatic stress disorder (PTSD) diagnosis and history of child abuse. Total Life Stress (TLS) was also assessed in all subjects. We evaluated DNA extracted from peripheral blood using the HumanMethylation27 BeadChip and analyzed both global and site-specific methylation. Methylation levels were examined for association with PTSD, child abuse history, and TLS using a linear mixed model adjusted for age, sex, and chip effects. Global methylation was increased in subjects with PTSD. CpG sites in five genes (TPR, CLEC9A, APC5, ANXA2, and TLR8) were differentially methylated in subjects with PTSD. Additionally, a CpG site in NPFFR2 was associated with TLS after adjustment for multiple testing. Notably, many of these genes have been previously associated with inflammation. Given these results and reports of immune dysregulation associated with trauma history, we compared plasma cytokine levels in these subjects and found IL4, IL2, and TNFα levels associated with PTSD, child abuse, and TLS. Together, these results suggest that psychosocial stress may alter global and gene-specific DNA methylation patterns potentially associated with peripheral immune dysregulation. Our results suggest the need for further research on the role of DNA methylation in stress-related illnesses., (Copyright © 2011 Wiley-Liss, Inc.)

Gene x environment (G x E) interactions mediating depressive symptoms have been separately identified in the stress-sensitive serotonergic (5-HTTLPR) and corticotropin-releasing hormone (CRHR1) systems. Our objective was to examine whether the effects of child abuse are moderated by gene x gene (G x G) interactions between CRHR1 and 5-HTTLPR polymorphisms. We used an association study examining G x G x E interactions of CRHR1 and 5-HTTLPR polymorphisms and measures of child abuse on adult depressive symptomatology. The participant population (N = 1,392) was African-American, of low socioeconomic status (60% with <$1,000/month family income), and with high rates of childhood and lifetime trauma. Depressive symptoms were measured with Beck Depression Inventory (BDI) and history of Major Depression by Structure Clinical Interview based on DSM-IV (SCID). We first replicated an interaction of child abuse and 5-HTTLPR on lifetime SCID diagnosis of major depression in a subsample (N = 236) of the study population-the largest African-American 5-HTTLPR cohort reported to date. We then extended our previously reported interaction with both a CRHR1 SNP (rs110402) and TCA haplotype interacting with child abuse to predict current symptoms (N = 1,059; P = 0.0089). We found that the 5-HTTLPR S allele interacted with CRHR1 haplotypes and child abuse to predict current depressive symptoms (N = 856, P = 0.016). These data suggest that G x E interactions predictive of depressive symptoms may be differentially sensitive to levels of childhood trauma, and the effects of child abuse are moderated by genetic variation at both the CRHR1 and 5-HTTLPR loci and by their G x G interaction.

The aim of the present study was to investigate the changes in the pituitary-thyroid axis (PTA) and the time course of the hormonal alterations in subjects with opioid dependence after abstinence. Blood samples from in-patients with opioid dependence and age- and sex-matched healthy controls were collected. The severity of opioid abuse and of withdrawal symptoms was assessed. Results were compared between patients with opioid dependence (n = 30) and healthy controls (n = 30). We found that free triiodothyronine and free thyroxine levels were comparable with healthy controls while thyroid-stimulating hormone (TSH) was lower in patients in acute opioid abstinence period. Also, TSH levels in patients remained lower than controls after 30 days of abstinence. These results indicate that PTA function is altered in opioid-dependent subjects. These data highlight the importance of screening the thyroid function for individuals with chronic opioid dependence.

The title compound, dicarbonyl-1kappa(2)C-di-mu-chloro-1:2kappa(4)Cl-[cis,cis-2(eta(4))-1,5-cyclooctadiene]dirhodium(I), [Rh(2)Cl(2)(C(8)H(12))(CO)(2)], consists of a dichloro-bridged dimer of rhodium, with a non-bonded Rh.Rh distance of 3.284 (2) A. One Rh atom is coordinated to two carbonyl ligands, while the other Rh atom is coordinated to the cyclooctadiene moiety.

Study Objective: To explore the value of high-dose methotrexate (MTX)., Subjects: Blast cells from 15 patients with acute lymphoblastic leukemia., Interventions: We compared uptake and polyglutamation of [3H]-MTX by freshly isolated leukemic blasts in vitro after 24-hour exposure to 1, 10, and 50 microM [3H]-MTX., Measurements and Main Results: Mean MTX uptake (pmol/10(6) cells) was 0.78 +/- 0.19, 2.3 +/- 0.54, and 5.9 +/- 1.9, respectively, and mean polyglutamation was 82%, 66%, and 46%. Consequently, mean MTX polyglutamates were 0.68 +/- 0.18, 1.5 +/- 0.47, and 2.2 +/- 0.67 pmol/10(6) cells. Three of 15 patient samples had no detectable polyglutamation of MTX at 50 microM but MTX polyglutamates were detectable at 1 microM. Two of these three had a decrease in MTX polyglutamates at 10 versus 1 microM. In eight precursor B cell samples there was a significant difference in median MTX polyglutamates at 1 versus 10 microM but not 10 versus 50 microM., Conclusion: Increasing extracellular MTX concentrations may be counterproductive for some patients with acute lymphoblastic leukemia. If MTX polyglutamates are important for efficacy, optimal delivery of MTX may have to be determined by individual metabolism rather than by targeting a specific drug concentration.

The accumulation of 5-methyl[3H]tetrahydrofolic acid (5CH3[3H]FH4) by phytohaemagglutinin stimulated lymphocytes (PHA-L) cultured in folate free media was investigated to determine the mechanism of uptake of 5CH3FH4 and the requirement of the cells for this vitamin as assessed by monitoring de novo thymidine synthesis. When grown in 20 nM 5CH3[3H]FH4 PHA-L accumulate radiolabel at a rate of 0.04 pmol/h/10(6) cells. This doubles the endogenous folate pool of unstimulated cells (0.6 +/- 0.16 pmol/10(6) cells) in about 15 h. Uptake proceeded via a saturable process, independent of a high affinity folate receptor as assessed by ligand binding and by Northern and Western blot analysis. However, transport was blocked by probenecid, which is consistent with an anion carrier mechanism. Unstimulated cells lacked folypolyglutamate synthetase (FPGS) activity and did not express significant amounts of FPGS mRNA. After 48 h of mitogen stimulation there was a 4-10-fold increase in FPGS mRNA and folypolyglutamate formation (Glu > or = 5) was essentially simultaneous with 5CH3[3H]FH4 transport. Increasing extracellular folate to 2 microM only increased intracellular folate 8-fold, but the length of the folylpolyglutamates decreased. The increased folate did not increase de novo thymidine synthesis compared to cells grown in physiological folate. We conclude that mitogen stimulation activates the process(es) for folate accumulation, especially FPGS, and that physiological uptake (0.04 pmol/h/10(6) cells) is adequate for meeting the cells' need for the vitamin.