Chronic adolescent stress causes sustained impairment of cognitive flexibility and hippocampal synaptic strength in female rats.

Females that experience chronic stress during development, particularly adolescence, are the most vulnerable group to stress-induced disease. While considerable attention has been devoted to stress-induced manifestation of anxiety, depression, and PTSD, evidence indicates that a history of chronic stress is also a risk factor for cognitive decline and dementia - with females again in a higher risk group. This interplay between sex and stress history indicates specific mechanisms drive neural dysfunction across the lifespan. The presence of sex and stress steroid receptors in the hippocampus provides a point of influence for these variables to drive changes in cognitive function. Here, we used a rodent model of chronic adolescent stress (CAS) to determine the extent to which CAS modifies glutamatergic signaling resulting in cognitive dysfunction. Male and female Wistar rats born in-house remained non-stressed (NS), unmanipulated aside from standard cage cleaning, or were exposed to either physical restraint (60 min) or social defeat (CAS) each day (6 trials each), along with social isolation, throughout the adolescent period (PND 35-47). Cognition was assessed in adult (PND 80-130) male and female rats (n = 10-12) using the Barnes Maze task and the Attention Set-Shift task. Whole hippocampi were extracted from a second cohort of male and female rats (NS and CAS; n = 9-10) and processed for RNA sequencing. Brain tissue from the first cohort (n = 6) was processed for density of glutamatergic synaptic markers (GluA1, NMDA1a, and synaptophysin) or whole-cell patch clamping (n = 4) to determine glutamatergic activity in the hippocampus. Females with a history of chronic stress had shorter latencies to locate the goal box than NS controls during acquisition learning but showed an increased latency to locate the new goal box during reversal learning. This reversal deficit persisted across domains as females with a history of stress required more trials to reach criterion during the reversal phases of the Attention Set-Shift task compared to controls. Ovariectomy resulted in greater performance variability overall during reversal learning with CAS females showing worse performance. Males showed no effects of CAS history on learning or memory performance. Bioinformatic prediction using gene ontology categorization indicated that in females, postsynaptic membrane gene clusters, specifically genes related to glutamatergic synapse remodeling, were enriched with a history of stress. Structural analysis indicated that CAS did not alter glutamate receptor density in females. However, functionally, CAS females had a decreased AMPA/NMDA-dependent current ratio compared to controls indicating a weakening in synaptic strength in the hippocampus. Males showed only a slight change in density of NMDA1a labeling in the CA3 region with a history of stress. The data observed here suggest that females are at risk for impaired cognitive flexibility following a history of adolescent stress, possibly driven by changes in glutamatergic signaling.

Blocking the VISTA pathway enhances disease progression in (NZB × NZW) F1 female mice.

V-domain Ig suppressor of T-cell activation (VISTA) is a critical negative checkpoint molecule involved in regulating the immune response. Targeting the pathway with an antagonist anti-VISTA antibody designated 13F3 has been shown to enhance disease severity in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. To determine if VISTA plays a role in murine lupus, New Zealand Black × New Zealand White (BWF1) mice were treated with 13F3 or control hamster Ig and disease monitored. Onset of proteinuria was earlier and renal damage more profound in mice treated with 13F3. Cell subset analysis showed an increase of activated splenic T cells and inflammatory splenic myeloid cells, but no effect on B cells, in mice receiving 13F3. Examination of the kidney showed an increase in inflammatory myeloid cell infiltration with 13F3 treatment. This study along with previous EAE data, suggests that interventions that enhance VISTA regulatory activity may be effective for the treatment of autoimmune disease.

Efficacy of on-farm use of ultraviolet light for inactivation of bacteria in milk for calves.

Ultraviolet light is being employed for bacterial inactivation in milk for calves; however, limited evidence is available to support the claim that UV light effectively inactivates bacteria found in milk. Thus, the objective of this observational study was to investigate the efficacy of on-farm UV light treatment in reducing bacteria populations in waste milk used for feeding calves. Samples of nonsaleable milk were collected from 9 Pennsylvania herds, twice daily for 15 d, both before and after UV light treatment (n=60 samples per farm), and analyzed for standard plate count, coliforms, noncoliform, gram-negative bacteria, environmental and contagious streptococci, coagulase-negative staphylococci, Streptococcus agalactiae, Staphylococcus aureus count, and total solids percentage, and log reduction and percentage log reduction were calculated. Data were analyzed using the mixed procedure in SAS. In all bacteria types, samples collected after UV treatment contained significantly fewer bacteria compared with samples collected before UV treatment. Weighted least squares means for log reduction (percentage log reduction) were 1.34 (29%), 1.27 (58%), 1.48 (53%), 1.85 (55%), 1.37 (72%), 1.92 (63%), 1.07 (33%), and 1.67 (82%) for standard plate count, coliforms, noncoliform, gram-negative bacteria, environmental and contagious streptococci, Strep. agalactiae, coagulase-negative staphylococci, and Staph. aureus, respectively. A percentage log reduction greater than 50% was achieved in 6 of 8 bacteria types, and 43 and 94% of samples collected after UV treatment met recommended bacterial standards for milk for feeding calves. Based on these results, UV light treatment may be effective for some, but not all bacteria types found in nonsaleable waste milk. Thus, farmers should take into account the bacteria types that may need to be reduced when considering the purchase of a UV-treatment system.

Neural steroid sensitivity and aggression: comparing individuals of two songbird subspecies.

Hormones coordinate the expression of complex phenotypes and thus may play important roles in evolutionary processes. When populations diverge in hormone-mediated phenotypes, differences may arise via changes in circulating hormones, sensitivity to hormones or both. Determining the relative importance of signal and sensitivity requires consideration of both inter- and intrapopulation variation in hormone levels, hormone sensitivity and phenotype, but such studies are rare, particularly among closely related taxa. We compared males of two subspecies of the dark-eyed junco (Junco hyemalis) for territorial aggression and associations among behaviour, circulating testosterone (T), and gene expression of androgen receptor (AR), aromatase (AROM) and oestrogen receptor α in three behaviourally relevant brain regions. Thus, we examined the degree to which evolution may shape behaviour via changes in plasma T as compared with key sex steroid binding/converting molecules. We found that the white-winged junco (J. h. aikeni) was more aggressive than the smaller, less ornamented Carolina junco (J. h. carolinensis). The subspecies did not differ in circulating testosterone, but did differ significantly in the abundance of AR and AROM mRNA in key areas of the brain. Within populations, both gene expression and circulating T co-varied significantly with individual differences in aggression. Notably, the differences identified between populations were opposite to those predicted by the patterns among individuals within populations. These findings suggest that hormone-phenotype relationships may evolve via multiple pathways, and that changes that have occurred over evolutionary time do not necessarily reflect standing physiological variation on which current evolutionary processes may act.

Neural sensitivity to sex steroids predicts individual differences in aggression: implications for behavioural evolution.

Testosterone (T) regulates many traits related to fitness, including aggression. However, individual variation in aggressiveness does not always relate to circulating T, suggesting that behavioural variation may be more closely related to neural sensitivity to steroids, though this issue remains unresolved. To assess the relative importance of circulating T and neural steroid sensitivity in predicting behaviour, we measured aggressiveness during staged intrusions in free-living male and female dark-eyed juncos (Junco hyemalis). We compared aggressiveness to plasma T levels and to the abundance of androgen receptor (AR), aromatase (AROM) and oestrogen receptor alpha (ORα) mRNA in behaviourally relevant brain areas (avian medial amygdala, hypothalamus and song control regions). We also asked whether patterns of covariation among behaviour and endocrine parameters differed in males and females, anticipating that circulating T may be a better predictor of behaviour in males than in females. We found that circulating T related to aggressiveness only in males, but that gene expression for ORα, AR and AROM covaried with individual differences in aggressiveness in both sexes. These findings are among the first to show that individual variation in neural gene expression for three major sex steroid-processing molecules predicts individual variation in aggressiveness in both sexes in nature. The results have broad implications for our understanding of the mechanisms by which aggressive behaviour may evolve.

Epidemiology of Mycoplasma bovis in Pennsylvania veal calves.

The objective of the study was to estimate the prevalence and incidence of Mycoplasma bovis, a common cause of pneumonia, in veal calves. Using simple random sampling, 252 calves from 4 veal herds located in central Pennsylvania were selected and longitudinally followed for monthly collection of nasal swabs. Bronchial swabs and lung lesions were collected at the slaughterhouse. Nasal, bronchial, and lung lesion swabs were cultured for bacterial respiratory pathogens. Ninety lung lesions were identified, of which 41.1, 1.1, 1.1, 7.8, and 4.4% were culture positive for M. bovis alone, Pasteurella multocida alone, Mannheimia haemolytica alone, M. bovis and P. multocida co-infection, and M. bovis and M. haemolytica co-infection, respectively. The data indicate that potential interventions, such as therapeutics, vaccines, or management control measures, would be most effective before 50 d of age based upon the cumulative incidence of colonization.

Changes in weight and waist circumference over 9 years in a Scottish population.

OBJECTIVE: To document patterns of measured weight and waist circumference (WC) change and the increase in overweight and obesity over a 9-year period. SUBJECTS/METHODS: A total of 1044 subjects from two age-defined cohorts aged 39 and 59 in 1991. Height, weight and WC were measured in 1991, 1995 and 2000 and body mass index (BMI) was calculated. Pattern of weight and WC change was studied over approximately 9 years. RESULTS: The prevalence of overweight and obesity increased markedly and the younger cohort showed greater increases in weight and WC than the older cohort. There was no significant difference in mean BMI and/or mean 9-year weight change between men and women in either age cohort, and mean weight gain was similar for all occupational groups. Only 20% of subjects maintained a stable weight (+/-2 kg), while 42.2 and 17.6% gained greater than 5 and 10 kg over the 9-year period, respectively. The rate of weight gain appeared to be relatively steady over the 9 years among younger subjects but declined in the older subjects in the second half of the observation period. CONCLUSIONS: Health promotion strategies to prevent weight gain need to be population-based, targeting all social and age groups, but particularly those in their early middle-age.

Measuring food access in Melbourne: access to healthy and fast foods by car, bus and foot in an urban municipality in Melbourne.

Access to healthy food can be an important determinant of a healthy diet. This paper describes the assessment of access to healthy and unhealthy foods using a GIS accessibility programme in a large outer municipality of Melbourne. Access to a major supermarket was used as a proxy for access to a healthy diet and fast food outlet as proxy for access to unhealthy food. Our results indicated that most (>80%) residents lived within an 8-10 min car journey of a major supermarket i.e. have good access to a healthy diet. However, more advantaged areas had closer access to supermarkets, conversely less advantaged areas had closer access to fast food outlets. These findings have application for urban planners, public health practitioners and policy makers.

Knowledge of treatment intent among patients with advanced cancer: a longitudinal study.

Increasingly, patients with cancer wish to be more fully informed about their disease, treatment and prognosis, and to participate in decision making. The objective of this study was to assess knowledge of diagnosis and goals of treatment among patients with advanced cancer, and also to assess whether this knowledge changed over time. A cohort of 181 subjects with advanced cancer receiving palliative therapies were interviewed at entry and again 12 weeks later. Knowledge of disease diagnosis, treatment intent, and the main sources of information were determined. Twenty per cent of subjects considered their illness to be non-life threatening, and 46% correctly perceived treatment intent as non-curative; 29% believed the intent of treatment was cure. Subjects resident in rural areas were more likely to misunderstand the goal of their treatment. Treatment modality was significantly associated with knowledge of treatment intent, and subjects in the last 6 months of life had clearer understanding that treatment intent was non-curative. Many patients with advanced cancer do not understand the goals of treatment. Excessive optimism may lead to impaired decision making. Further empirical research into information transfer and predictors of accurate patient understanding would assist clinicians in their discussions of prognosis and potential treatment outcomes with patients.

Evaluation of IS900-PCR assay for detection of Mycobacterium avium subspecies Paratuberculosis infection in cattle using quarter milk and bulk tank milk samples.

A study was conducted to evaluate sensitivity, specificity, and predictive value of IS900-PCR assay for detection of Mycobacterium avium subspecies paratuberculosis in pooled quarter milk and bulk tank milk. Feces, blood and pooled quarter milk from 1493 lactating cattle on 29 herds were analyzed. Bulk tank milk (n = 29 bulk tanks) samples were also examined. Culture analysis revealed that 10.9%, 2.8%, and 20.6% of fecal, pooled quarter milk samples and bulk tanks were positive for M. avium subsp. paratuberculosis, respectively. While 13.5% and 27.5% of pooled quarter milk samples and bulk tanks were positive by IS900 PCR assay, respectively. Moderate to high antibody titers for M. avium subsp. paratuberculosis were detected in 223 of 1493 (14.4%) cows. Cows positive on fecal culture were taken as true positives relative to which the IS900 PCR assay was evaluated. The sensitivity and predictive value of KELA, pooled quarter milk culture, and IS900 PCR assay increased with lactation age. While the specificity of the tests decreased with increase in lactation age. Overall, the IS900 PCR assay using pooled quarter milk samples had a sensitivity, specificity and predictive value of 0.87, 0.95 and 0.71, respectively. The IS900 PCR assay using bulk tank milk had poor sensitivity (0.21), specificity (0.5) and predictive value (0.6). Pooled quarter milk culture analysis had a very low sensitivity (0.17). The kinetics ELISA had lower sensitivity (0.59), specificity (0.90) and predictive value (0.43) as compared to the IS900 PCR assay using pooled quarter milk samples. Results from our study suggest that IS900 PCR assay using bulk tank milk may not be useful for screening herds with M. avium subsp. paratuberculosis infected animals. In conclusion, use of IS900 PCR assay for cows in 2(nd) lactation and higher, using aseptically collected pooled quarter milk samples, can be a useful tool for screening and monitoring lactating cattle in herds with M. avium subsp. paratuberculosis infection.

Food cost and availability in a rural setting in Australia.

INTRODUCTION: The burden of chronic diseases is rapidly increasing worldwide. In Australia rural populations have a greater burden of disease. Chronic diseases are largely preventable with diet as a key risk factor. With respect to diet-related chronic disease, dietary risk may be due to poor food access, namely, poor availability and/or the high cost of healthy food. It is likely that poor food access is an issue in rural areas. OBJECTIVE: To assess food access in rural south-west (SW) Victoria, Australia. METHODS: A total of 53 supermarkets and grocery stores in 42 towns participated in a survey of food cost and availability in the rural area of SW Victoria. The survey assessed availability and cost of a Healthy Food Access Basket (HFAB) which was designed to meet the nutritional needs of a family of 6 for 2 weeks. RESULTS: Seventy-two percent of the eligible shops in SW Victoria were surveyed. The study found that the complete HFAB was significantly more likely to be available in a town with a chain-owned store (p <0.00). The complete HFAB was less likely to be available from an independently owned store in a town with only one grocery shop (p <0.004). The average cost of the HFAB across SW Victoria was AU380.30 dollars +/- 25.10 dollars (mean +/- SD). There was a mean range in difference of cost of the HFAB of 36.92 dollars. In particular, high variability was found in the cost of fruits and vegetables. CONCLUSIONS: Cost and availability of healthy food may be compromised in rural areas. IMPLICATIONS: Improvements in food access in rural areas could reduce the high burden of disease suffered by rural communities.

The relationship between quality of life and perceived body weight and dieting history in Dutch men and women.

OBJECTIVES: (1) To study the relationship between quality of life (QoL) and measured and perceived weight and dieting history in Dutch men and women; (2) to assess the effect of weight loss over a 5 y period on QoL. DESIGN: A cross-sectional study, in a sub-sample longitudinal over 5 y. SUBJECTS: A total of 2155 men and 2446 women, aged 20-59 and recruited from the general population from three towns in The Netherlands. MEASUREMENTS: Body weight, height, self-administered questionnaire including questions concerning demographic variables and weight loss practices as part of the Dutch Monitoring project on Risk Factors for Chronic Disease (MORGEN). The Rand-36 questionnaire was used as the QoL measure. RESULTS: In men, measured overweight (body mass index, BMI>25 kg/m(2)) was not associated with any dimension of QoL after adjustment for age, educational level and perceived overweight. Perceived overweight was related to reduced scores for general health and vitality. This relationship was independent of measured obesity. A history of repeated weight loss was associated with reduced scores for role functioning due to both physical and emotional problems. In women, measured overweight was significantly associated with lower scores for five out of eight QoL dimensions and perceived overweight with three: general health, vitality and physical functioning. A history of frequent weight loss was related to significantly reduced scores in six dimensions. However, only with history of frequent weight loss, and uniquely in women, was there a significant reduction in scores on mental health and limited emotional role functioning. Measured and perceived overweight and frequent weight loss were all related to reduced scores for physical functioning. Longitudinal data indicate that in older women weight gain of 10% body weight or more was associated with a significant deterioration in QoL. CONCLUSIONS: When looking at measures of QoL in relation to overweight it is important to separate the effects of perception of weight status and history of weight loss. We observed that the latter two factors were associated with reduced scores on several dimensions of QoL, particularly in women. These associations were observed to be independent of body weight.

Modeling a medical environment: an ontology for integrated medical informatics design.

Modern medical environments have seen an increase in technological complexity and pressures of handling more patients with fewer resources, resulting in higher demands on medical practitioners. Medical informatics designers will have to focus on the problem of organizing medical information more effectively to enable practitioners to cope with these challenges. This article addresses this research problem for the particular area of medical problem solving in patient care. First, we describe a traditional modeling approach for medical reasoning used as a basis for developing some decision support systems. We argue these models may be faithful to what is known about biomedical knowledge, but they have limitations for human problem solving, especially in unanticipated situations. Second, we present an ontological framework, known as the abstraction hierarchy (Rasmussen, IEEE Trans. Man. Cybernetics 15 (1985) 234-243), for integrating patient representations that are faithful to existing biomedical knowledge and that are consistent with what is known about human problem solving. Through an example of a critical event in the operating room, we reveal how this framework can support medical problem solving in unanticipated situations. Third, we show how to use these representations as a frame of reference for mapping medical roles, responsibilities, sensors, and controls in an operating room context. Finally, we provide some insight for medical informatics designers in using this framework to design novel training programs and human-computer displays.

Penetrating neck injuries: analysis of experience from a Canadian trauma centre.

OBJECTIVE: To study the demographics and treatment outcome of penetrating neck injuries presenting to a major trauma centre in order to develop a treatment protocol. DESIGN: A case review. SETTING: A trauma centre at a tertiary care institution. PATIENTS: One hundred and thirty consecutive patients who had 134 neck wounds penetrating the platysma and presented to the trauma service between 1979 and 1997. INTERVENTION: Surgical exploration or observation alone. MAIN OUTCOME MEASURES: The location of injury, patient management, number of significant injuries, duration of hospital stay and outcome. RESULTS: Injuries were caused by stab wounds in 124 patients (95%) and gunshot wounds in 6 (5%). The location of injury was zone I (lower neck) in 20 cases (15%), zone II (midportion of the neck) in 108 (81%) and zone III (upper neck) in 5 (4%). The location was not recorded in 1 case. Fifty patients were managed by observation alone and 80 were managed surgically. Neck exploration in 48 asymptomatic patients was negative in 32 (67%). Significant injuries, including major vascular (12), nerve (13) and aerodigestive tract (19) injuries, were identified in 34 patients. Two of the 130 patients (1.5%) died of major vascular injuries. Seventy-six percent of significant injuries, including all zone II major vascular injuries, were symptomatic on presentation. The mean (and standard deviation) hospital stay for asymptomatic patients treated with observation alone and surgical exploration was similar (3.5 [6.02] versus 4.3 [5.46] days respectively, p = 0.575). Long-term disability, all neurologic in nature, was documented in 3 patients managed by observation alone and 6 patients managed by surgical exploration. CONCLUSIONS: Penetrating neck trauma, in particular stab wounds to zone II in asymptomatic patients, is associated with low morbidity and mortality. A selective management protocol with investigations directed by symptoms is the most appropriate approach for the patient population and resource base in this setting.

The nucleoid-associated protein StpA binds curved DNA, has a greater DNA-binding affinity than H-NS and is present in significant levels in hns mutants.

The StpA protein is closely related to H-NS, the well-characterised global regulator of gene expression which is a major component of eubacterial chromatin. Despite sharing a very high degree of sequence identify and having biochemical properties in common with H-NS, the physiological function of StpA remains unknown. We show that StpA exhibits similar DNA-binding activities to H-NS. Although both display a strong preference for binding to curved DNA, StpA binds DNA with a four-fold higher affinity than H-NS, with K(d)s of 0.7 microM and 2.8 microM, respectively. It has previously been reported that expression of stpA is derepressed in an hns mutant. We have quantified the amount of StpA protein produced under this condition and find it to be only one-tenth the level of H-NS protein in wild-type cells. Our findings explain why the presence of StpA does not compensate for the lack of H-NS in an hns mutant, and why the characteristic pleiotropic hns mutant phenotype is observed.

Putting it all together: improving display integration in ecological displays.

Computer displays are being designed for increasingly larger industrial systems. As the application domain scales up, maintaining integration across different kinds of views becomes more challenging. This paper presents the results of a study of three different approaches to integration based on the spatial and temporal proximity of related information objects. The domain used for evaluation was a simulation of an industry-scale conventional power plant. All three displays were ecological displays developed using an abstraction hierarchy analysis. Views were integrated in a high-space/low-time, low-space/high-time, and high-space/high-time integration of means-end related objects. During a fault detection and diagnosis task, it was found that a low level of integration, high-space/ low-time, provided the fastest fault detection time. However, the most integrated condition, high-space/high-time, resulted in the fastest and most accurate fault diagnosis performance. Actual or potential applications of this research include computer displays for large-scale systems such as network management or process control, for which problem solving is critical and integration must be maintained.

There is more to monitoring a nuclear power plant than meets the eye.

A fundamental challenge in studying cognitive systems in context is how to move from the specific work setting studied to a more general understanding of distributed cognitive work and how to support it. We present a series of cognitive field studies that illustrate one response to this challenge. Our focus was on how nuclear power plant (NPP) operators monitor plant state during normal operating conditions. We studied operators at two NPPs with different control room interfaces. We identified strong consistencies with respect to factors that made monitoring difficult and the strategies that operators have developed to facilitate monitoring. We found that what makes monitoring difficult is not the need to identify subtle abnormal indications against a quiescent background, but rather the need to identify and pursue relevant findings against a noisy background. Operators devised proactive strategies to make important information more salient or reduce meaningless change, create new information, and off-load some cognitive processing onto the interface. These findings emphasize the active problem-solving nature of monitoring, and highlight the use of strategies for knowledge-driven monitoring and the proactive adaptation of the interface to support monitoring. Potential applications of this research include control room design for process control and alarm systems and user interfaces for complex systems.

Determination of the free-energy change for repair of a DNA phosphodiester bond.

The repair of phosphodiester bonds in nicked DNA is catalyzed by DNA ligases. Ligation is coupled to cleavage of a phosphoanhydride bond in a nucleotide cofactor resulting in a thermodynamically favorable process. A free energy value for phosphodiester bond formation was calculated using the reversibility of the T4 DNA ligase reaction. The relative number of DNA nicks to phosphodiester bonds in a circular plasmid DNA, formed during this reaction at fixed concentrations of ATP to AMP and PP(i), was quantified. At 25 degrees C, pH 7, the equilibrium constant (K(eq)) for the ligation reaction is 3.89 x 10(4) m. This value corresponds to a standard free energy (DeltaG degrees ') of -6.3 kcal mol(-1). By subtracting the known energy contribution due to hydrolysis of ATP to AMP and PP(i), DeltaG degrees ' for the hydrolysis of a DNA phosphodiester bond is -5.3 kcal mol(-1).

A participant-observer study of ergonomics in engineering design: how constraints drive design process.

Too often, ergonomics is relegated to being a "post-design" evaluation, leaving ergonomists little opportunity to make significant and important design changes. One way to start attacking this problem is to study the process of design and, in particular, ergonomics in design. This article describes the findings from a four-month long participant-observer study of the relationship between ergonomics and engineering design. The study was conducted in the context of a large, interdisciplinary project consisting of design of a control room for a nuclear power plant. It was observed that designers and ergonomists must negotiate through a changing web of constraints from many sources. The impact that these constraints had on the course of the design was documented. A model is developed based on the abstraction hierarchy (Rasmussen, 1985, IEEE Trans. Systems Man Cybernet. SMC-15, 234-243; 1990, Int. J. Ind. Ergon. 5, 5-16) which shows the interaction of conflicting goals as ergonomists and other designers attempt to solve a complex design problem. This model leads to several insights: (1) locally optimal ergonomic designs may not be globally optimal, (2) ergonomists can improve their solutions by understanding the goals of other designers, and (3) future tools to aid ergonomists must be compatible with the constraint-rich environments in which they work.