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The data presented here was produced as part of an evaluation of the performance of the CoaguChek XS point-of-care coagulation analyzer, which is discussed in the research article “POCT PT INR – Is it adequate for Patient Care? A Comparison of the Roche Coaguchek XS vs. Stago Star vs. Siemens BCS in Patients Routinely Seen in an Anticoagulation Clinic” (Baker et al., in press) [1] . An effort to reconcile discrepancies in the patient INR result distributions from different central lab instruments (Stago Star and Siemens BCS) with the PT/INR line method is described (Poller et al., 2010, 2011; Ibrahim et al., 2011) [2] , [3] , [4] . While regression analysis of the ECAA Poller calibrant data provided a linear PT/INR line for all methods, Pearson's chi-squared and one-way repeated measures ANOVA analyses showed that central lab INR measurements continued to exhibit measurement site dependence after the PT/INR line correction was applied. According to paired t-test analysis, only the human thromboplastin dependent methods (CoaguChek XS and Siemens BCS both before and after PT/INR line correction) showed statistically significant agreement (p-value >0.05).

Disrupted neural synchrony may be a primary electrophysiological abnormality in autism spectrum disorders (ASD), altering communication between discrete brain regions and contributing to abnormalities in patterns of connectivity within identified neural networks. Studies exploring brain dynamics to comprehensively characterize and link connectivity to large-scale cortical networks and clinical symptoms are lagging considerably. Patterns of neural coherence within the Default Mode Network (DMN) and Salience Network (SN) during resting state were investigated in 12 children with ASD (MAge = 9.2) and 13 age and gender-matched neurotypicals (NT) (MAge = 9.3) with magnetoencephalography. Coherence between 231 brain region pairs within four frequency bands (theta (4-7 Hz), alpha, (8-12 Hz), beta (13-30 Hz), and gamma (30-80 Hz)) was calculated. Relationships between neural coherence and social functioning were examined. ASD was characterized by lower synchronization across all frequencies, reaching clinical significance in the gamma band. Lower gamma synchrony between fronto-temporo-parietal regions was observed, partially consistent with diminished default mode network (DMN) connectivity. Lower gamma coherence in ASD was evident in cross-hemispheric connections between: angular with inferior/middle frontal; middle temporal with middle/inferior frontal; and within right-hemispheric connections between angular, middle temporal, and inferior/middle frontal cortices. Lower gamma coherence between left angular and left superior frontal, right inferior/middle frontal, and right precuneus and between right angular and inferior/middle frontal cortices was related to lower social/social-communication functioning. Results suggest a pattern of lower gamma band coherence in a subset of regions within the DMN in ASD (angular and middle temporal cortical areas) related to lower social/social-communicative functioning. Autism Res 2018, 11: 434-449. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY Communication between different areas of the brain was observed in children with ASD and neurotypical children while awake, but not working on a task. Magnetoencephalography was used to measure tiny magnetic fields naturally generated via brain activity. The brains of children with ASD showed less communication between areas that are important for social information processing compared to the brains of neurotypical children. The amount of communication between these areas was associated with social and social communication difficulties.

Behavioral intervention is the only treatment for pediatric feeding problems with well documented empirical support. However, parents may be hesitant to pursue behavioral intervention because of concerns about possible negative side effects on child behavioral health and the parent-child relationship. This study investigated associations between behavioral feeding treatment and parenting stress, internalizing and externalizing behavior problems in young children, and parent-child attachment quality.Participants included 16 mother-child dyads seeking treatment from a behavioral feeding clinic at a large Midwestern university medical center. Children were between the ages of 30 and 45 months (adjusted) at baseline. Caregivers completed the Child Behavior Checklist for ages 1.5 to 5 (CBCL/1.5-5), the Parenting Stress Index, 3rd Edition Short Form (PSI/SF), and mother-child dyads participated in the Strange Situation procedure at baseline and again after 6 months. The treatment group (n = 12) began outpatient behavioral feeding intervention following the baseline evaluation, whereas the control group (n = 12) remained on the clinic waitlist until after the 6-month follow-up.The treatment group demonstrated decreases in internalizing and externalizing child behavior problems and parenting stress compared with the control group. No significant differences were demonstrated in parent-child attachment quality within or between groups.Behavioral feeding intervention had positive effects on perceptions of child emotional and behavioral functioning and maternal parenting stress. Intervention also did not impact the quality of the mother-child attachment relationship. Further research with a larger sample size and additional observational measures of behavior is needed to support the replicability and generalizability of these results.

In this study we examined the difference in patient INR values as measured by the POCT CoaguChek XS device and central laboratory Stago Evolution and Siemens BCS XP analyzers.This study composed of 100 warfarin therapy patients and 20 coagulation normal subjects, showed that the difference between the POCT and clinical laboratory values increased with increasing INR and was exacerbated by the use of different thromboplastin reagents by the POCT and central lab.The CoaguChek XS and on-site Stago analyzers which used human recombinant (ISI=1.01) and rabbit brain thromboplastin (ISI=1.25), respectively, showed reasonable agreement for INR3.0 (k=0.62) but significant difference for INR≥3.0 (k=0.10). In contrast, the CoaguChek XS and Siemens BCS XP, which both employed human recombinant thromboplastin (BCS ISI=1.02), showed greater agreement for the complete range INR values (INR3.0 k=0.84; INR≥3.0 k=0.70). ECAA Poller calibrant data showed the automated instruments were performing as expected, indicating that ISI calibrations were correct but insufficient to standardize the INR values for the different thromboplastin methods across the full range of measured INRs. Central lab verification of POCT INR5.0 with the Stago Evolution prevented adverse treatment events for the warfarin therapy patients in the six months preceding and following this investigation.

Human rhinovirus (HRV) is one of the most common human respiratory pathogens and is responsible for the majority of upper respiratory illnesses. Recently, a phylogeny was constructed from all known American Type Culture Collection (ATCC) HRV sequences. From this study, three HRV classifications (HRVA, HRVB, and HRVC) were determined and techniques for classifying new isolates of HRV were reported. The genetic change of this virus in specific populations over time is of great interest to understand the evolution and epidemiology of viruses. To facilitate the collections of HRV sequences over a number of years, a virology experiment was designed in which students test nasal lavage samples to look for HRV infection. Students will learn a variety of techniques including RNA isolation, cDNA synthesis, qPCR, and agarose gel electrophoresis as well as bioinformatic skills though examination of sequences from the HRV‐field isolates. Furthermore, students can look at symptom data from subjects to investigate correlations between symptom severity and factors such as stress and sleep patterns. Such information can be used to examine hypotheses regarding HRV mutation, symptom severity and epidemiology. BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION Vol. 39, No. 6, pp. 457–458, 2011

Conjugated linoleic acid (CLA) has a number of beneficial biological effects, including reducing cancer incidence and development, reducing severity of atherosclerosis, modulating immune responses, reducing body fat, and enhancing lean mass. Recently CLA has been reported to have a beneficial effect on blood pressure. Thus the effects of CLA supplementation on blood pressure and its associated adverse health effects using spontaneously hypertensive rats were investigated. Results indicated that CLA had no effect on blood pressure in this animal model. However, feeding CLA significantly reduced the incidence and number of animals with stroke-like symptoms. Although the reason CLA reduced stroke-like symptoms is not clear at this moment, there is great potential that CLA may be useful in reducing stroke incidence in humans.

This exploratory study examines the experience of motherhood in the context of spinal cord injury (SCI), utilizing data from survey measures and qualitative interviews. Based on scores on standardized measures of perceived stress and life satisfaction, 19 mothers with SCI were assigned to one of four quadrants in a 2 x 2 matrix depicting various patterns of adjustment involving high or low satisfaction with life and high or low levels of perceived stress. Content analysis of the women’s narratives further describes their social adjustment, psychological adaptation, and quality of life following SCI in connection with the role of

Despite the attention depression after spinal cord injury (SCI) has received, research and clinical practice have been hampered by inadequate emphasis on reliable and valid measurement. Assessment of symptoms in persons with SCI is challenged by the presence of "trans-diagnostic" symptoms and unexamined effects of gender. The objective of this study was to examine the factor structure of the Patient Health Questionnaire-9 (PHQ-9; the 9-item depression scale of the Patient Health Questionnaire) and determine whether the structure replicates across gender.A total of 1,168 women and men were matched on level/completeness of SCI, follow-up year, and age to create 584 pairs. Exploratory factor analysis examined 1- and 2-factor models and congruence in 2 randomly split half samples to establish congruence of the factor solution and replication across gender.The 1- and 2-factor solutions fit the structure of the items accounting for 41% to 51% of original item variance. Congruence between random samples was uniformly high for the 1-factor solution (r = 0.791-0.948) but variable for the 2-factor solution. Although congruence was high for the combined sample and men (r = 0.90-0.97 and 0.71-0.94, respectively), it was variable for women (r = 0.29-0.85).Although there was support for the 1-factor structure of the PHQ within and between sexes, the low congruence between sexes and within women for the 2-factor structure indicates potentially important differences about how certain symptoms may be experienced or interpreted differently, by men and women with SCI. Future research should focus on where sexes diverge in cognitive, affective, and somatic dimensions of depressive symptoms and whether sex-specific or sex-neutral measures are warranted.

The health benefits of ω-3 fatty acids, particularly fish oils, are well known. It is generally recommended to obtain ω-3 fatty acids from fatty fish; however, the possible contaminants in fish products may deter this. Thus, supplements of ω-3 fatty acids from plant-originated lipids may be of interest. Among these, α-linolenic acid (ALA) and stearidonic acid (SDA) have drawn attention. Thus, the purpose of this research was to test the possible conversion of these fatty acids, particularly SDA, to eicosapentaenoic acid (EPA) using a human hepatoma cell line, HepG2 cells. In addition, even though ω-3 fatty acids have been shown to reduce hyperlipidemia, the effects on lipoprotein metabolism are relatively inconsistent. Thus, we also tested ω-3 fatty acids along with SDA on apolipoprotein A and B (apo A and B) secretion from this cell line. The results obtained suggest that both ALA and SDA were converted to EPA and they increased apo B secretion, while having no effect on apo A secretion, similar to the effects of EPA and docosahexaenoic acid. Thus, it may be concluded that SDA can be a possible candidate for use as a precursor for EPA and its effect on lipoproteins was similar to that of EPA. PRACTICAL APPLICATIONS This study suggests the possible use of stearidonic and α-linolenic acids from plant-originated fat as precursors for eicosapentaenoic acid, promoting health benefits as alternatives for fish consumption.

In previously studies, we showed that tumor necrosis factor-α (TNF-a), a cytokine involved in a variety of biologically important events, is partially involved in the effects of conjugated linoleic acid (CLA). In this report, we further tested the effects of individual CLA isomers on serum TNF-a concentration along with other biological markers in mice. The animals were fed experimental diets (control, 0.5% CLA-mixed isomer, 0.25% cis-9, trans-11 CLA or 0.25% trans-10, cis-12 CLA) for 5 days and were then challenged with endotoxin. Both cis-9, trans-11 and trans-10, cis-12 CLA isomers reduced serum TNF-a levels compared to control. CLA had no effect on the other biological markers examined. These results suggest possible early involvement of CLA in immune and/or inflammatory responses, followed by reduction of body fat. Its effect on TNF-a helps explain in part how CLA modulates other biological functions such as immune response, insulin responses, atherosclerosis and cancer.

Purpose This study describes the prevalence of probable major depressive disorder (MDD) as well as other depressive disorders (ODD) and severity of depressive symptoms in a national sample of women with spinal cord injury (SCI) and compares them with a case-matched sample of men with SCI. Methods A sample of 585 women was drawn and case-matched with men from the SCI Model System National SCI Database according to level/completeness of injury, follow-up year, and age. The outcome measure of depression was the Patient Health Questionnaire. Main Findings Prevalence rates for women were 7.9% for probable MDD and 9.7% for ODD; rates for men were 9.9% and 10.3%, respectively. Logistic regression revealed that women who were divorced or at year 1 follow-up had a higher odds of having probable MDD (odds ratio [OR], 3.4 and 2.9, respectively). Employed women and men had significantly lower odds of probable MDD (OR, 0.274 and 0.358, respectively). Statistically significant differences were not found in gender comparisons for either probable MDD or symptom severity, which also were not associated with injury characteristics. Conclusion The most significant, and unexpected, research finding is the absence of gender differences in probable MDD and symptom severity. Results challenge notions that depression will necessarily follow SCI; that injury characteristics determine the development and severity of depression; and that women experience a greater burden of depression than men. The main clinical implication is that depression screening and referral should be a routine feature of health care for women living with SCI, as well as for their male counterparts. Furthermore, nearly one fourth of women and men reported experiencing some or greater difficulty in daily life and relationships in the absence of probable depressive disorder, warranting monitoring of subsyndromal depression as well.

Natural transmission of the epizootic ulcerative syndrome (EUS) was conducted on naïve snakeheads Ophicephalus striatus (also known as Channa striata) kept (A) in aquifer water, (B) in lakewater, (C) cohabiting with EUS snakeheads in lakewater, and (D) cohabiting with apparently healthy snakeheads in lakewater during the 1994 to 1995 EUS season. The results showed that EUS-like lesions developed in 6 to 14 d among naïve snakeheads cohabiting with EUS snakeheads and with apparently healthy snakeheads in lakewater (Treatments C and D). Among naïve fish exposed to lakewater (Treatment B), similar lesions developed in 16 to 21 d, while naïve fish in aquifer water (Treatment A) did not develop EUS-like lesions. EUS signs began as Grade I (slight) lesions that gradually progressed to Grades III-IV (severe) 3 to 5 d from lesion onset, similar to the naturally affected EUS fish. The virus was recovered from some but not all naturally EUS-affected snakeheads, snakeheads with healing lesions and apparently healthy snakeheads, but not from naïve snakeheads. The results provide evidence of a waterborne horizontal transmission of the EUS-associated virus. This is the first report of a successful horizontal transmission of the EUS-associated virus from apparently healthy snakeheads to naïve fish under natural conditions and of virus recovery in tissue culture from naturally exposed experimental fish.

We compared the effects of dietary conjugated linoleic acid (CLA) on body composition in weanling hamsters and rats fed 20% fat (HF) or 5% fat (LF) diets for 9 weeks. In both species the HF groups appeared to gain more body weight and fat relative to the LF groups but the differences were not significant. In hamsters fed LF or HF, total body fat gain was significantly reduced by CLA-supplementation (0.5% or 1% of diet). Body weight gain was also reduced, but the differences were significant only in the HF group. Feed intake appeared not to be affected for any group. In rats fed HF or LF diet, total body fat was not reduced by CLA supplementation (1% of diet) but the lipid stored in specific fat pads was significantly reduced (for the LF-CLA group the retroperitoneal and omentum fat pads were significantly reduced; for the HF-CLA group the peritoneal fat pad was significantly reduced). Body weight gain and feed intake were not affected except for the LF-CLA group where feed intake was significantly reduced. These results indicate that body fat gain in both hamsters and rats is reduced by CLA feeding, and that hamsters are more responsive than rats in this regard. It is important now to determine the biochemical basis for these differences.

To assess the impact of preanalytical variables of time and temperature on prothrombin time (PT), activated partial thromboplastin time (aPTT), dilute Russell viper venom time (DRVVT), activated protein C resistance (APCR), and d-dimer, samples from 23 healthy individuals and 18 patients having coagulopathy with known abnormal PT and aPTT were collected. Plasma from each individual was separately pooled and aliquoted; the first 2 aliquots were stored at room temperature then analyzed at 2 hours (baseline) and 4 hours postcollection. The remaining aliquots were stored at −20°C and thawed for analysis at 48 hours, 1, and 2 weeks. In both healthy participants and participants with coagulopathy, PT, aPTT, APCR, DRVVT, and D-dimer had no significant changes at 4 and 48 hours, and 1 and 2 weeks postcollection compared to baseline, or the changes were less than 10%. The results indicate PT, aPTT, DRVVT, APCR, and d-dimer can be stored for 2 weeks at −20°C without compromising clinical interpretation in both healthy individuals and individuals with coagulopathy. Increasing storage time will facilitate sample processing from off-site clinics.

Identification of a small animal model that undergoes pathological temporomandibular joint (TMJ) degeneration would represent a significant research tool. To date however, no such model has been described. We therefore have investigated the pathological and immunohistochemical features of the TMJ of a transgenic mouse that over expresses the human form of TNFα. The TMJ of this animal appears to undergo changes that resemble arthriditics of temporomandibular dysfunction. Furthermore, the disc and articular cells express MMP9 and IL-1. Future work should validate this animal model as one that would have utility for the study of TMJ disorders. Maintenance of connective tissues in joints such as the TMJ is a normal process that allows for the reconstitution of important anatomic features. This maintenance involves both the removal and re-synthesis of structural proteins such as collagens, elastins and proteoglycans. An imbalance in the pathways for degradation and synthesis can lead to the degeneration of joint tissues. We describe the presence of a matrix metalloproteinase, MMP9 (92-kD gelatinase), in TMJ disc and articular cells that likely function in the degradative process. Additionally, we show that this enzyme is under the control of pro-inflammatory cytokines whereby TGFβ and IL-1 stimulate and PGE2 inhibits its activity.

The rhabdoviruses isolated from EUS-affected snakeheads in the Philippines was tested for pathogenicity to healthy, naive snakehead Ophicephalus striatus fry, fingerlings and juveniles. Virus exposure of naive snakehead fry and fingerlings by bath at 20-22.5°C resulted in significant mortalities (pl0.01) with no apparent lesions. Naive snakehead juveniles when injected intramuscularly (IM) with the EUS-associated rhabdovirus at ambient water temperature (28-32°C) did not develop any lesion. However, similarly treated snakehead juveniles at 20-22.5°C developed dermal lesions 3-5 days following treatment. The lesions progressed from slight to moderately advanced lesions by days 10-12 but not to deep ulcers as exhibited by naturally EUS-affected snakeheads. Mean mortalities were higher in the virus-injected fish (72%) compared to those in controls (33%). Moreover, the virus was reisolated from fish in the 20-22.5°C treatment but not from fish in the 28-32°C treatment. Virus from infected tissue filtrate and the virus passaged 3 or 4 times induced similar dermal lesions if the rhabdovirus concentration was 103 TCID50/fish or higher. When administered orally, by bath, by intraperitoneal (IP), IM and subdermal injections to snakehead juveniles, only the latter two viral routes induced dermal lesions. However, IP injection of the rhabdovirus caused 75% mortalities but none in control fish. The results demonstrate the pathogenicity of the rhabdovirus isolates to naive snakeheads at low (20-22.5°C) rearing water temperatures.

Two experiments were conducted. In Experiment 1, 8-wk-old mice were fed control diet or diet supplemented with 0.5% conjugated linoleic acid (CLA) to study the effect of CLA on body composition (CLA: 40.8-41.1% c-9,t-11 isomer, 43.5-44.9% t-10,c-12 isomer). The data for CLA-fed mice vs. controls described parallel but significantly distinct responses for both absolute and relative changes in body fat mass (reduced in CLA-fed mice) and for relative changes in whole body protein and whole body water (both of which were increased in CLA-fed mice). In the CLA-fed mice, the effect on whole body protein appeared to precede the reduction in body fat mass. In Experiment 2, weanling mice were fed control diet or diet supplemented with 0.5% CLA for 4 wk (test group), at which time all mice were fed control diet devoid of added CLA. The test group exhibited significantly reduced body fat and significantly enhanced whole body water relative to controls at the time of diet change. Time trends for changes in relative body composition were described by parallel lines where the test group exhibited significantly less body fat but significantly more whole body protein, whole body water, and whole body ash than controls. Tissue CLA levels declined following the withdrawal of CLA from the diet. In skeletal muscle of mice fed CLA-supplemented diet, the t-10,c-12 isomer was cleared significantly faster than the c-9,t-11 CLA isomer.

Summary Isolates of Aquaspirilluni sp., Pseudomonas sp., and Streptococcus sp. recovered from epizootic ulcerative syndrome (EUS)-affected snakeheads (Ophicephalus striatus) in Thailand as well as an isolate of Aeromonas hydrophila recovered from EUS-affected snakeheads in the Philippines were characterized and identified. Each isolate was injected intramuscularly (IM) into healthy catfish (Clarias batrachus) and snakeheads (O. striatus). Results showed in tests with C. batraclius that 24 h after injection, Aquaspirillum sp., Pseudomonas sp., Streptococcus sp. and A. hydrophila induced slight, slight, moderate and severe dermomuscular necrotic lesions, respectively. Among O. striatus, only A. hydrophila induced severe lesions. Streptococcus sp. induced slight lesions 2 days post-injection which healed rapidly, while Aquaspirillum sp. and Pseudonionas sp. did not manifest any dermal lesions. Experiments indicated that among the four EUS-associated test bacteria, A. hydrophila was the most pathogenic, inducing severe dermomuscular necrotic lesions in intramuscularly injected catfish (C. batrachus) and snakeheads (O. striatus). Differences in the susceptibility of O. striatus and C. batrachus to Aquaspirillum sp., Pseudomonas sp. and Streptococcus sp. were evident. Furthermore, this is the first evidence of the association between Aquaspirillum sp. and diseased fish.

The effects of conjugated linoleic acid (CLA) on body composition were investigated. ICR mice were fed a control diet containing 5.5% corn oil or a CLA-supplemented diet (5.0% corn oil plus 0.5% CLA). Mice fed CLA-supplemented diet exhibited 57% and 60% lower body fat and 5% and 14% increased lean body mass relative to controls (P < 0.05). Total carnitine palmitoyltransferase activity was increased by dietary CLA supplementation in both fat pad and skeletal muscle; the differences were significant for fat pad of fed mice and skeletal muscle of fasted mice. In cultured 3T3-L1 adipocytes CLA treatment (1 x 10(-4)M) significantly reduced heparin-releasable lipoprotein lipase activity (-66%) and the intracellular concentrations of triacylglyceride (-8%) and glycerol (-15%), but significantly increased free glycerol in the culture medium (+22%) compared to control (P < 0.05). The effects of CLA on body composition appear to be due in part to reduced fat deposition and increased lipolysis in adipocytes, possibly coupled with enhanced fatty acid oxidation in both muscle cells and adipocytes.

Previously it was reported that 4-hydroxy-2 (or 5)-ethyl-5 (or 2)-methyl-3(2H)-furanone (HEMF), a characteristic flavour component of Japanese-style fermented soy sauce that exhibits antioxidant activity, inhibits benzo[a]pyrene-induced forestomach neoplasia in mice. The antioxidant and anticarcinogenic activities of other structurally similar soy sauce flavour components are now reported. 4-Hydroxy-5-methyl-3(2H)-furanone (HMF) and 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) were found to be antioxidants. In particular, HMF and HDMF (as well as HEMF) reduced hydrogen peroxide concentration in human polymorphonuclear leucocytes stimulated by arachidonic acid or 12-O-tetradecanoylphorbol-13-acetate. HMF and HDMF were administered individually in semipurified diet to female ICR mice previously treated with benzo[a]pyrene (1.5 mg/wk, orally for 4 wk) to initiate forestomach neoplasia. The mice were killed at 30 wk of age. Both furanones reduced forestomach neoplasms, with HDMF exhibiting more potency. The data indicate that HDMF and HMF, like HEMF, inhibit carcinogenesis in this system by acting at the post-initiation stage.

Buspirone is a nonbenzodiazepine anxiolytic that has been effective in uncontrolled trials for treating childhood anxiety disorders. A 4-year-old boy with a history of laryngomalacia (congenital structural abnormality with airway collapse and obstruction on inhalation), pharyngeal dysphagia (difficulty in swallowing), poor weight gain, delayed self-feeding skills, and anxiety symptoms is described. An open trial of buspirone, increased gradually to 12.5 mg daily in divided doses over a period of 22 weeks, was associated with decreased anxiety, improved self-feeding skills, and weight gain. Based on parental reports, buspirone appeared to decrease separation and social anxiety, as well as anxiety associated with eating. Drug discontinuation was associated with symptom relapse, whereas drug readministration lead to the same clinical benefits that had been observed previously. The medication was well tolerated, and its benefits have persisted for over 1 year. No new recommendations can be made regarding the use of buspirone in preschool children or in the treatment of anxious behaviors adversely affecting medical conditions in children and adolescents.

Changes in plasma cortisol concentrations and inter-renal and chromaffin tissues of rainbow trout, Oncorhynchus mykiss (Walbaum), exposed to harmful concentrations of the diatom Chaetoceros concavicornis were investigated. The plasma cortisol level of trout exposed to C. concavicornis was over 10-fold greater than that of untreated trout. Computer-assisted feulgen-microspectrophotometry was employed in order to assess the activity of inter-renal and chromaffin cells. The total areas of inter-renal and chromaffin nuclei in trout treated with C. concavicornis significantly increased compared to those of untreated fish. In contrast, the chromatin density of inter-renal and chromaffin nuclei in treated trout decreased significantly. This decrease of chromatin density in treated fish was caused by an increase in the low-density components, and a decrease in the middle-density and high-density components. Although the hypertrophic changes to the inter-renal and chromaffin nuclei of treated fish exhibited the same general trend, the extents to which the changes took place were different, occurring more rapidly within inter-renal tissues. The rainbow trout exposed to harmful concentrations of C. concavicornis were experiencing a severe physiological disturbance to which they tried to adapt.

The effects of misregistration artifacts and background corrections on the densitometric measurement of left ventricular ejection fraction (EF) from digital subtraction angiography (DSA) images were studied in 20 patients. Densitometric ejection fraction measurements were performed on both conventional time subtraction images and on dual-energy subtraction images. Dual-energy subtraction is not sensitive to the motion induced artifacts which often mar time subtraction images. While the time subtraction images had varying degrees of misregistration artifacts, none of the dual-energy studies contained significant misregistration artifacts. Densitometrically determined ejection fractions measured with and without correction for background signals were compared. Poor agreement between time subtraction ejection fractions determined with and without background correction (EFNO-BKG = 0.88 EFBKG - 6.0%, SEE = 8.1%, r = 0.83) demonstrated the sensitivity of time subtraction EFs to the performance of a background correction procedure. Conversely, densitometric measurement of ejection fraction using dual-energy subtraction was significantly less sensitive to the performance of a background correction (EFNO-BKG = 0.99 EFBKG - 5.3%, SEE = 4.3%, r = 0.96). Since background correction requires accurate definition of ventricular borders, but motion artifacts often preclude accurate border definition, it is concluded that dual-energy subtraction is a significantly more robust method for measuring left ventricular ejection fraction using densitometry. It is further concluded that identification of the systolic endocardial border is not required when performing densitometric EF measurements on dual-energy images. Drawing of the end-diastolic border alone is sufficient to produce an accurate ejection fraction measurement.

The harmful phytoplankters Chaetoceros concavicornis and Chaetoceros convolutus are normal components of the phytoplankton assemblage along the British Columbia coast. During 1988, these diatoms occurred at their highest concentrations in the spring and fall from the Strait of Georgia to Queen Charlotte Strait. North of Queen Charlotte Strait, the maximal concentrations appeared to be delayed until summer. The greatest concentrations occurred in the waters of the Strait of Georgia and its contiguous bays and inlets, especially Jervis Inlet, where concentrations of C. concavicornis and C. convolutus which could be harmful to salmon occurred during the spring and fall of 1988. Lesser concentrations occurred in coastal seawaters north of the Strait of Georgia. These phytoplankters were absent, or were present in only minor concentrations, in inlets with low-salinity waters such as Holberg Inlet and Indian Arm. Harmful Chaetoceros cells were restricted to seawaters greater than approximately 17‰ salinity. Vertically and horizontally well-mixed waters, such as those of Johnstone Strait, also appeared to restrict the presence of these cells. The greatest concentrations of these diatoms occurred during the spring and fall in relatively stratified coastal seawater with salinities between 26 and 34‰.

Objective Examine the diurnal variation of salivary cortisol in adults with spinal cord injury (SCI) and the effect of stressors on cortisol and mood. Method Ecological momentary assessment (EMA) to capture cortisol, stress, and mood from 25 persons with SCI and 26 without SCI. Data were analyzed using linear mixed models. Results There were no systematic differences between groups on missing data. Diurnal variation of cortisol of participants with SCI reflected an expected pattern. No significant group differences for cortisol diurnal pattern, stress, or mood; when group interactions were significant, results indicated lower cortisol reactivity to stress in participants with SCI. Stress had a significant impact on positive, negative and agitated moods. Conclusions Stress in daily life and its association with cortisol and mood were largely similar between persons with and without SCI. A key methodological contribution is the demonstration of using EMA to collect biological and behavioral data in the field from participants with SCI. The use of EMA in rehabilitation psychology research has great potential to advance our understanding of the dynamics of daily life with disability.

We previously reported that fluorouracil (5FU) accumulation and metabolism in human livers and tumors can be studied by in vivo nuclear magnetic resonance spectroscopy (NMRS). We have extended these observations by evaluating the pharmacokinetics of 5FU in the tumors of 11 patients with carcinoma of the breast, colon, endometrium, cervix, and kidney, using 19F-NMRS in a 1.5 Magnetom (Siemens Medical Systems, Cerrito, CA) magnetic resonance imaging unit (MRI). These NMRS measurements detected a long-lived tumor pool of 5FU in six of 11 tumors in our patients including carcinomas in the pelvis, breast, lung, and liver. The half-life (T1/2) of this tumor pool of "trapped" 5FU was 0.33 to 1.3 hours (20 to 78 minutes), much longer than the T1/2 of 5FU in blood (5 to 15 minutes). Neither the anabolites of 5FU (fluorinated nucleosides, nucleotides, 5FU-RNA, or 5FU-thymidylate synthase) nor the catabolites (eg, fluorobetaalanine [FBAL]) were detectable by 19F NMRS. Patient response to chemotherapy appeared to correlate with the extent of trapping of free 5FU in the human tumors: in the seven patients receiving 5FU, or 5FU or FUdR plus leucovorin, four of four patients whose tumors trapped 5FU responded to fluorinated pyrimidine chemotherapy, whereas three patients in whom there was a failure to detect tumor trapping were resistant to 5FU. We conclude that NMRS is clinically feasible, and enables investigators to study 5FU pharmacokinetics and metabolism in tumors in vivo. 19F-NMRS of 5FU allows for in vivo evaluation of 5FU metabolic modulation and might be able to guide therapeutic decisions.

The pharmacokinetics of 5-fluorouracil (5FU) were studied in vivo in patients with discrete tumors and in rabbits bearing VX2 tumors by using 19F NMR spectroscopy. The human studies were conducted in a 1.5-T Magnetom magnetic resonance imager (Siemens), and the rabbit studies were conducted in a 4.7-T GE/Nicolet 33-cm bore magnet. Free 5FU was detected in the tumors of four of the six patients and in all VX2 tumors but not in normal rabbit tissues. No other metabolites were seen in these tumors, contrary to the extensive catabolism we had previously documented using 19F NMR spectroscopy in both human and animal livers. The tumor pool of free 5FU in those human tumors that trapped 5FU was determined to have a half-life of 0.4-2.1 hr, much longer than expected and significantly longer than the half-life of 5FU in blood (5-15 min), whereas the half-life of trapped 5FU in the VX2 tumors ranged from 1.05 to 1.22 hr. In this initial experience, patient response to chemotherapy may correlate with extent of trapping free 5FU in the human tumors. These studies document that NMR spectroscopy is clinically feasible in vivo, allows noninvasive pharmacokinetic analyses at a drug-target tissue in real time, and may produce therapeutically important information at the time of drug administration. Demonstration of the trapping of 5FU in tumors provides both a model for studying metabolic modulation in experimental tumors (in animals) and a method for testing modulation strategies clinically (in patients).

Weanling male Fischer 344 rats were fed either control or diet containing 1% CLA for 18 months. Weight gain and survival rate were not different between treatments, but CLA-fed animals ate slightly less food. CLA feeding did not significantly reduce body fat compared to that of control. Clinical chemistry and hematology analyses were performed on blood samples at week 69–72. CLA had no effects except on blood glucose, which was reduced in CLA-fed animals compared to control. All animals had chronic renal failure at the end of the study; however, CLA decreased the amount of protein in urine at week 70 of feeding. Necropsy and histo-pathology results indicated that there was no difference between treatment groups. Although this study used a limited number of animals and a single dose of CLA, our results suggest that long term CLA feeding did not cause any adverse effects in rats.

The trans-10,cis-12 isomer of conjugated linoleic acid (CLA) has been shown to reduce body fat gain in mice. However, the underlying molecular mechanism is not well characterized. Here we report evidence that trans-10,cis-12 (t10c12) CLA inhibits preadipocyte differentiation. Treating differentiating 3T3-L1 preadipocytes with t10c12 CLA and conjugated nonadecadienoic acid (CNA, a 19-carbon CLA cognate) resulted in decreased intracellular triglyceride accumulation and mRNA levels of the adipogenic gene fatty acid synthase and adipocyte lipid binding protein. T10c12 CLA and CNA also reduced protein levels of adipocyte transcription factors, peroxisome proliferator-activated receptor gamma and CCAAT/enhancer binding protein alpha. Similarly, CLA reduced body fat gain and significantly inhibited the expression of PPAR gamma and its downstream target lipoprotein lipase in mouse adipose tissue. These observations indicate that CLA decreases body fat gain in part by inhibiting the differentiation of preadipocytes.

Two experiments were conducted to determine the conjugated linoleic acid (CLA) content of milk from cows offered diets rich in linoleic and linolenic acid. In experiment 1, 36 cows were assigned to a control and five treatment groups. Cows in the control group received a diet containing 51% forage and 49% grain on a dry matter basis. In the treatment group, grain was partly replaced by either 18% raw cracked soybeans, 18% roasted cracked soybeans, 3.6% soybean oil, 2.2% linseed oil, or 4.4% linseed oil. Experimental diets were fed for 5 wk. Average CLA contents in milk fat from wk 2 through 5 were 0.39% in control and 0.37, 0.77, 2.10, 1.58, and 1.63% of total fatty acids in the raw soybean, roasted soybeans, soybean oil, 2.2% linseed oil, and 4.4% linseed oil treatments, respectively. In experiment 2, 36 cows were assigned to a control and 5 treatment groups. Cows in the control group received a diet containing 55% forage and 45% grain. In the treatment groups, grain was partly replaced by soybean oil at 0.5, 1.0, 2.0, 4.0, or by linseed oil at 1.0% of the dietary dry matter. Experimental diets were fed for 5 wk. Average CLA contents in milk fat from wk 2 through 5 were 0.50% in control and 0.75, 0.76, 1.45, 2.08, and 0.73% of total fatty acids in 0.5, 1.0, 2.0, 4.0 soybean oil and 1.0% linseed oil treatments, respectively. Diets rich in linoleic or linolenic acid can increase CLA content of milk when dietary oil is accessible to the rumen microorganisms.

The ultimate fate of the expanded pool of osteoblasts formed following a typical bone injury is unclear. Since necrosis has not been described in the latter stages of bone healing, there must be some other mechanism by which obsolete osteoblasts are cleared from an injury site. We therefore evaluated the possibility that their removal is pre-programmed, by investigating the occurrence of apoptosis in rats that received a standardized bone injury. Histological evidence identical to that found in tissues known to exhibit apoptosis was obtained, thereby showing that programmed cell death was a normal concomitant of fracture healing. The concentration of apoptotic bodies reached its maximum after the differentiative response had peaked, suggesting that the two processes were coordinated. The same result was found in a second group of rats that received the same bone injury plus a simultaneous standardized soft-tissue injury. The combined injuries resulted in more osteoblasts and more apoptotic bodies, but an identical temporal relationship between the peak responses in the two parameters. The results suggested that osteoblasts were removed from the injury site via apoptosis, and that the process was coordinately regulated with differentiation. Since the number of apoptotic bodies per osteoblast varied during healing, it is likely that apoptosis was associated with healing and not merely with osteoblast concentration.

Densitometric analysis of images obtained by digital subtraction angiography (DSA) allows for more reproducible and less operator-dependent quantitation of ventricular function. Conventional DSA uses temporal subtraction but is limited by misregistration artifacts. Dual-energy digital subtraction angiography (DE-DSA) is immune to such misregistration artifacts. The ability of DE-DSA to quantitate changes in regional ventricular volume resulting from ischemia was tested. Densitometric analysis of both phase-matched and ejection fraction DE-DSA images was used to quantitate regional left ventricular systolic function during four levels of ischemia ranging from mild to severe in open-chest dogs (n = 10). DE-DSA left ventriculograms were obtained by means of central venous injections of iodinated contrast medium. Ischemia was graded according to percentage of systolic wall thickening as measured by sonomicrometry. Phase-matched end-systolic images were obtained at each of four levels of ischemia by subtracting an end-systolic control image from each end-systolic ischemic image. Ejection fraction images were obtained at the control level and at each level of ischemia by subtracting an end-systolic image from an end-diastolic image of the same cardiac cycle. The resulting wall motion difference signals represent the changes in regional ventricular volumes and were quantitated by densitometry. Densitometry was able to detect the effect of all levels of ischemia on regional function, even the mildest. Densitometric analysis of both phase-matched and ejection fraction DE-DSA images provides a sensitive technique for detecting and quantitating the changes in regional left ventricular systolic volume that occur with ischemia.

Conjugated dienoic derivatives of linoleic acid (referred to by the acronym CLA) constitute a newly recognized class of anticarcinogenic fatty acids. Of the eight major CIA isomere, the cis-9, trans-11 isomer alone is incorporated into phospholipid and may to be the most biologically relevant isomer. CLA exhibits potent antioxidant activity; evidence is presented indicating that CLA acts both as an in vitro and in vivo antioxidant. The formation of CLA in foods, and its possible biological significance in cell membranes, is discussed.

Digital subtraction angiography (DSA) allows quantitative analysis of ventricular function via densitometric and parametric imaging techniques. However, DSA is limited by the artifacts in temporal subtraction images that result from patient and cardiac motion. Dual-energy subtraction imaging is insensitive to motion. This study evaluated the initial application of dual-energy subtraction in cardiac patients. The image quality of dual-energy subtraction left ventriculograms obtained from a pulmonary artery injection of contrast was assessed in 13 patients, ranging in weight from 54 to 100 kg. The dual-energy images were compared with left ventricular images obtained using standard left ventricular injection cine angiography. End-systolic and end-diastolic ventricular volumes calculated from the cine (C) and dual-energy (DE) images using the Area-Length method were compared. The resulting regression line was DE = 0.98 C+ 7.0 ml, and the r value was 0.987. Dual-energy subtraction provided good left ventricular visualization, free from misregistration artifacts, even during patient motion.