Metabolomic analysis of heat-hardening in adult green-lipped mussel (Perna canaliculus): A key role for succinic acid and the GABAergic synapse pathway.

We evaluated the thermotolerance (LT50) of adult green-lipped mussels (Perna canaliculus) following an acute thermal challenge in the summer of 2012 and the winter of 2013. Mussels were grouped into two treatments, naïve (N, no prior heat treatment) and heat-hardened (HH = 1 h at 29 °C, 12 h recovery at ambient) before being immersed for 3 h in water of varying temperature, i.e. Ambient (Control), 25, 29, 31, 33, and 35 °C with subsequent mortality monitored for 30 days. As expected, naïve mussels were less thermotolerant than heat-hardened i.e. Summer LT50, N = 31.9, HH = 33.5 °C; Winter LT50, N = 31.4, HH = 33.8 °C. Moreover, at 33 °C no heat-hardened mussels died compared to 100% mortality in naïve specimens. At 35 °C all mussels died regardless of treatment. For the 'Summer' mussels, metabolite abundances in gill tissues of both naïve and heat-hardened mussels were quantified. For mussels at 33 °C, succinic acid was significantly higher in naïve mussels than heat-hardened mussels, indicating perturbations to mitochondrial pathways in these thermally stressed mussels. Additionally, analysis of biochemical pathway activity suggested a loss of neural control i.e. significantly reduced GABAergic synapse activity, in naïve vs. heat-hardened mussels at 33 °C. Taken together these findings suggest that heat-hardening improves mussel survival at higher temperatures by delaying the onset of cellular anaerobic metabolism, and by maintaining inhibition of neural pathways. Such results offer new perspectives on the complex suite of sub-cellular stress responses operating within thermally stressed organisms.

A Review of Studies on the System-Wide Implementation of Evidence-Based Psychotherapies for Posttraumatic Stress Disorder in the Veterans Health Administration.

Since 2006, the Veterans Health Administration (VHA) has instituted policy changes and training programs to support system-wide implementation of two evidence-based psychotherapies (EBPs) for posttraumatic stress disorder (PTSD). To assess lessons learned from this unprecedented effort, we used PubMed and the PILOTS databases and networking with researchers to identify 32 reports on contextual influences on implementation or sustainment of EBPs for PTSD in VHA settings. Findings were initially organized using the exploration, planning, implementation, and sustainment framework (EPIS; Aarons et al. in Adm Policy Ment Health Health Serv Res 38:4-23, 2011). Results that could not be adequately captured within the EPIS framework, such as implementation outcomes and adopter beliefs about the innovation, were coded using constructs from the reach, effectiveness, adoption, implementation, maintenance (RE-AIM) framework (Glasgow et al. in Am J Public Health 89:1322-1327, 1999) and Consolidated Framework for Implementation Research (CFIR; Damschroder et al. in Implement Sci 4(1):50, 2009). We highlight key areas of progress in implementation, identify continuing challenges and research questions, and discuss implications for future efforts to promote EBPs in large health care systems.

D-chiro-inositol attenuates epinephrine-stimulated hepatic glucose output in the isolated perfused liver independently of insulin.

D-chiro-Inositol (DCI) is a cyclic sugar alcohol that evokes both antidiabetic and insulin sensitizing effects. Pharmacological administration of DCI has been shown to lower blood glucose in rat models of diabetes mellitus and enhance insulin sensitivity in humans with polycystic ovary syndrome (PCOS). We hypothesised that the antidiabetic effects of DCI could be due to inhibition of hepatic glucose output (HGO). To test this hypothesis, we perfused isolated rat livers either with buffer, myo-inositol, DCI, or insulin, and investigated their respective effects on the stimulation of HGO by epinephrine. We found that perfusion with 200 µM DCI attenuated epinephrine-stimulated HGO by 35% over 30 min as compared to the buffer control perfusion (p=0.05). By comparison, perfusion with 1 nM insulin attenuated epinephrine-stimulated HGO by 57% (p<0.0001). The glucose-lowering effects by DCI occurred independently of insulin and were specific to the DCI stereoisomer as 200 µM myo-inositol had no effect. These findings suggest that DCI could evoke its antidiabetic effects in vivo by inhibition of HGO. Further identification of the protein targets involved could open up new avenues to regulate hyperglycaemia with wider implications for the treatment of hepatic insulin resistance in PCOS.

Transmural differences in respiratory capacity across the rat left ventricle in health, aging, and streptozotocin-induced diabetes mellitus: evidence that mitochondrial dysfunction begins in the subepicardium.

In diabetic cardiomyopathy, ventricular dysfunction occurs in the absence of hypertension or atherosclerosis and is accompanied by altered myocardial substrate utilization and depressed mitochondrial respiration. It is not known if mitochondrial function differs across the left ventricular (LV) wall in diabetes. In the healthy heart, the inner subendocardial region demonstrates higher rates of blood flow, oxygen consumption, and ATP turnover compared with the outer subepicardial region, but published transmural respirometric measurements have not demonstrated differences. We aim to measure mitochondrial function in Wistar rat LV to determine the effects of age, streptozotocin-diabetes, and LV layer. High-resolution respirometry measured indexes of respiration in saponin-skinned fibers dissected from the LV subendocardium and subepicardium of 3-mo-old rats after 1 mo of streptozotocin-induced diabetes and 4-mo-old rats following 2 mo of diabetes. Heart rate and heartbeat duration were measured under isoflurane-anesthesia using a fetal-Doppler, and transmission electron microscopy was employed to observe ultrastructural differences. Heart rate decreased with age and diabetes, whereas heartbeat duration increased with diabetes. While there were no transmural respirational differences in young healthy rat hearts, both myocardial layers showed a respiratory depression with age (30-40%). In 1-mo diabetic rat hearts only subepicardial respiration was depressed, whereas after 2 mo diabetes, respiration in subendocardial and subepicardial layers was depressed and showed elevated leak (state 2) respiration. These data provide evidence that mitochondrial dysfunction is first detectable in the subepicardium of diabetic rat LV, whereas there are measureable changes in LV mitochondria after only 4 mo of aging.

Copper(II)-selective chelation improves function and antioxidant defences in cardiovascular tissues of rats as a model of diabetes: comparisons between triethylenetetramine and three less copper-selective transition-metal-targeted treatments.

AIMS/HYPOTHESIS: Treatment with the Cu(II)-selective chelator triethylenetetramine (TETA) improves cardiovascular disease in human patients, and cardiac and vascular/renal disease in rats used as a model of diabetes. Here we tested two hypotheses: first, that TETA elicits greater improvement in organ function than less Cu-selective transition-metal-targeted treatments; second, that the therapeutic actions of TETA are consistent with mediation through suppression of oxidative stress. METHODS: Rats were made diabetic with streptozotocin (55 mg/kg, i. v.) and treated from 8 weeks after disease induction for the following 8 weeks with effective dosages of oral TETA, or one of three less Cu-selective transition-metal-targeted treatments: D-penicillamine, deferiprone or Zn acetate. Treatment effects were measured in ex vivo cardiac and aortic tissues, plasma and urine. RESULTS: Diabetes damaged both cardiac and renal/vascular function by impairing the ability of cardiac output to respond physiologically to rising afterload, and by significantly elevating the urinary albumin/creatinine ratio. Diabetes also lowered total antioxidant potential and heparan sulphate levels in cardiac and arterial tissues, and serum ferroxidase activity, whereas it elevated urinary heparan sulphate excretion. TETA treatment rectified or partially rectified all these defects, whereas the other three experimental treatments were ineffectual. By contrast, none of the four drug treatments lowered diabetes-mediated elevations of plasma glucose or lipid concentrations. CONCLUSIONS/INTERPRETATION: TETA may limit the cardiac and renal/vascular damage inflicted by diabetes through its actions to reinforce antioxidant defence mechanisms, probably acting through selective chelation of 'loosely-bound'/chelatable Cu(II). It may also improve heparan sulphate homeostasis and bolster antioxidant defence by increasing vascular extracellular superoxide dismutase activity. Urinary albumin/creatinine ratio might prove useful for monitoring TETA treatment.

The antibacterial effect of photodynamic therapy in dental plaque-derived biofilms.

BACKGROUND AND OBJECTIVE: Photodynamic therapy has been advocated as an alternative to antimicrobial agents to suppress subgingival species and to treat periodontitis. Bacteria located within dense biofilms, such as those encountered in dental plaque, have been found to be relatively resistant to antimicrobial therapy. In the present study, we investigated the ability of photodynamic therapy to reduce the number of bacteria in biofilms by comparing the photodynamic effects of methylene blue on human dental plaque microorganisms in the planktonic phase and in biofilms. MATERIAL AND METHODS: Dental plaque samples were obtained from 10 subjects with chronic periodontitis. Suspensions of plaque microorganisms from five subjects were sensitized with methylene blue (25 microg/mL) for 5 min then exposed to red light. Multispecies microbial biofilms developed from the same plaque samples were also exposed to methylene blue (25 microg/mL) and the same light conditions as their planktonic counterparts. In a second set of experiments, biofilms were developed with plaque bacteria from five subjects, sensitized with 25 or 50 microg/mL of methylene blue and then exposed to red light. After photodynamic therapy, survival fractions were calculated by counting the number of colony-forming units. RESULTS: Photodynamic therapy killed approximately 63% of bacteria present in suspension. By contrast, in biofilms, photodynamic therapy had much less of an effect on the viability of bacteria (32% maximal killing). CONCLUSION: Oral bacteria in biofilms are affected less by photodynamic therapy than bacteria in the planktonic phase. The antibacterial effect of photodynamic therapy is reduced in biofilm bacteria but not to the same degree as has been reported for treatment with antibiotics under similar conditions.

A copper(II)-selective chelator ameliorates diabetes-evoked renal fibrosis and albuminuria, and suppresses pathogenic TGF-beta activation in the kidneys of rats used as a model of diabetes.

AIMS/HYPOTHESIS: The selective Cu(II) chelator triethylenetetramine (TETA) extracts systemic Cu(II) into the urine of diabetic humans and rats as a model of diabetes, and in the process also normalises hallmarks of diabetic heart disease. However, the role of Cu and its response to TETA in animals with diabetic nephropathy were previously unknown. Here, we report the effects of TETA treatment on Cu and other essential elements, as well as on indices of renal injury and known pathogenic molecular processes, in kidneys from a rat model of diabetes. METHODS: Rats at 8 weeks after streptozotocin-induction of diabetes were treated with oral TETA (34 mg/day in drinking water) for a further 8 weeks and then compared with untreated diabetic control animals. RESULTS: Renal tissue Cu was substantively elevated by diabetes and normalised by TETA, which also suppressed whole-kidney and glomerular hypertrophy without lowering blood glucose. The urinary albumin: creatinine ratio was significantly elevated in the rat model of diabetes but lowered by TETA. Total collagen was also elevated in diabetic kidneys and significantly improved by TETA. Furthermore, renal cortex levels of TGF-beta1, MAD homologue (SMAD) 4, phosphorylated SMAD2, fibronectin-1, collagen-III, collagen-IV, plasminogen activator inhibitor-1 and semicarbazide-sensitive amine oxidase all tended to be elevated in diabetes and normalised by TETA. CONCLUSIONS/INTERPRETATION: Dysregulation of renal Cu homeostasis may be a key event eliciting development of diabetic nephropathy. Selective Cu(II) chelation can protect against pathogenic mechanisms that lead to or cause diabetic nephropathy and might be clinically useful in the treatment of early-stage diabetic kidney disease.

Effect of housing system and boar exposure on estrus expression in weaned sows.

Reproductive efficiency depends on detection of estrus, which may be influenced by housing and boar exposure. This experiment investigated the effects of housing system and boar contact on measures of estrus in weaned sows. Mixed-parity sows were randomly assigned to be weaned into gestation crates away from boars (AWC, n = 45), into pens away from boars (AWP, n = 42), or into pens adjacent to a mature boar (ADJ, n = 46). Estrus detection was initiated at approximately 0700 (0 h) and again at 0.25-, 0.5-, 1-, 2-, 4-, and 8-h intervals beginning on d 4 and continuing through d 7 following weaning. Estrus detection involved observation of the standing response after application of nose-to-nose boar exposure, backpressure, and side rubbing. For the AWC sows, a mature boar was moved to the front of the crates for a 10-min period and then removed. Sows housed in AWP were moved approximately 15 m to an empty pen adjacent to a mature boar for a 10-min period, and then returned to their pen. Sows housed ADJ were not moved and estrus detection was performed in their home pen for a 10-min period. The proportion of sows expressing estrus within 7 d from weaning was lowest for ADJ (80%, 37/46) compared with AWP (98%, 41/42) and AWC (96%, 43/45; P < 0.05). There was an effect of interval from weaning to estrus on the percentage of sows expressing estrus, but there was no interaction with treatment. Sows in AWC and AWP (4.7 d) had decreased (P = 0.01) intervals from weaning to estrus compared with ADJ (5.2 d). The duration of estrus was also shorter (P < 0.001) for ADJ (45 h) compared with AWC (58 h) or AWP (62 h). There was a treatment x interval x day of estrus effect for the percentage of sows expressing estrus. After detection of the first standing response on the first day of estrus, only 62 to 82% of sows were detected standing over the next 2 h for all treatments. However, at 4 to 8 h, this increased to 85 to 98% for the AWC and AWP sows, but <73% of the ADJ sows were detected during this period. On the second day of estrus, estrus expression was not influenced by interval for the AWC and AWP sows and was between 90 to 100% during the 8-h period, whereas ADJ sow detection rates were between 68 to 88%. These data suggest that housing sows adjacent to boars negatively affects estrus expression and detection. In addition, refractory behavior occurs in approximately 30 to 40% of sows and is influenced by housing relative to the boar, day of estrus, and interval from last boar exposure.

Sexual abuse characteristics associated with survivor psychopathology.

OBJECTIVE: This study was designed to examine predictors of psychopathology in non-clinically referred, sexually abused (SA) children, ages 6-16 years, 30-60 days following abuse disclosure and termination. METHOD: Eighty SA children were administered a structured diagnostic interview and a variety of rating-scale instruments. Several forms of psychopathology were assessed, including posttraumatic stress, global functioning, anxiety, depression, and externalizing behavior. Abuse interviews also were used to guide the collection of demographic (victim age, gender) and abuse-related information (e.g., frequency of abuse). RESULTS: Abuse-related factors and demographic variables accounted for greater than half of the variance predicting global functioning, and accurately predicted posttraumatic stress disorder (PTSD) status for 86% of the participants. Also, analyses yielded significant predictors of parent-reported attention problems and sexual behavior. Of additional importance, none of the abuse-related and demographic variables predicted scores on measures of general anxiety, depression, and externalizing behavior. CONCLUSIONS: Specific demographic and sexual abuse information may, to some extent, be used to identify children who are at increased risk for short-term post-abuse psychopathology. Although the present findings suggest that such information may not be useful in the prediction of general anxiety, depression, and externalizing behavior, demographic and abuse-related variables importantly appear to account for significant variance in the prediction of global functioning, posttraumatic stress, attentiveness, and sexual behavior. Additional research is needed to improve mental health professionals' ability to identify SA children who are at high risk for psychopathology.

PTSD scale of the Child Behavior Checklist: concurrent and discriminant validity with non-clinic-referred sexually abused children.

Several assessment instruments include measures that are purported to assess characteristics of posttraumatic stress disorder (PTSD). Although these measures are used often by researchers and clinicians, few are supported by extensive validity data. The PTSD scale of the Child Behavior Checklist (CBCL) is one that has not yet encountered significant challenges to its validity. We examine the concurrent and discriminant validity of the CBCL-PTSD scale. Participants included 63 non-clinic-referred sexually abused (SA) children, 60 non-SA psychiatric outpatient children, and 61 non-SA, non-clinic-referred schoolchildren. Results revealed questionable concurrent validity for this scale, and suggest poor discriminant validity between SA children and non-SA psychiatric outpatients.

Now you see it, now you don't: explicit versus implicit measures of the personal/group discrimination discrepancy.

When making explicit self-report ratings, members of status- and racial-minority groups report less personal experience with discrimination than that encountered by their group--a phenomenon called the personal/group discrimination discrepancy (PGDD). This study provides evidence, for the first time, that the PGDD may be, in part, a product of the procedure used to measure it. White women and men completed explicit and implicit measures of personal and group discrimination based on sex. The PGDD surfaced among women in the explicit measures, but not in the implicit measures. These findings suggest that explicit and implicit measures might provide different assessments of experience with discrimination.

Less pain and more to gain: why high-status group members blame their failure on discrimination.

Members of high-status groups are more likely than members of low-status groups to blame their failure on discrimination and are less likely to blame it on themselves. This tendency was demonstrated in 3 experiments comparing men and women, White and Black students, and members of experimentally created high- and low-status groups. Results also showed that when making an attribution to discrimination, high-status group members were less likely to experience a threat to their social state self-esteem, performance perceived control, and social perceived control and were more likely to protect their performance state self-esteem. These findings help to explain why high-status group members are more willing to blame their failure on discrimination by showing that it is less harmful for them than for low-status group members.

Discriminant validity of self-reported anxiety and depression in children: generalizability to clinic-referred and ethnically diverse populations.

In the present study, we investigated the relation of childhood anxiety and depression with 240 children (56% clinical referrals, 44% nonclinical referrals) ages 8 to 14 years. Participants were administered the State-Trait Anxiety Inventory for Children (STAIC) and the Children s Depression Inventory (CDI), two commonly used self-report measures of childhood anxiety and depression. The principal focus of this study was to examine the discriminant validity of these measures at the level of individual items through factor analysis. Although high correlations were found between overall scores on the CDI and STAIC, factor analysis yielded distinct factors of anxiety and depression. Thus, with the inclusion of clinic-referred and ethnically diverse groups, the present study provided support for the generalizability of findings of similar research with non-clinic-referred, primarily-Caucasian samples.

Using item analysis to facilitate interpretation of empirical findings.

Researchers often present and interpret empirical findings with reference to hypothetical constructs and diagnostic labels. Such interpretations commonly are based upon "summary" scores obtained through interview, self-report, or rating-scale assessment instruments. Although there are advantages associated with communicating empirical findings through analysis with summary scores, there also are weaknesses that may limit the interpretability of empirical findings and impede theory development. We discuss the importance of item analysis as a tool that may guide presentation of empirical findings, and we describe how it may be used to minimize these limitations of assessment, facilitate data interpretation, and increase the opportunity for theoretical advances.

Psychopathology in non-clinically referred sexually abused children.

OBJECTIVE: To determine the prevalence of psychiatric symptoms and disorders found in non-clinically referred, sexually abused children (nCR-SAC), aged 6 to 16 years, during the 30- to 60-day period after disclosure and termination of abuse. METHOD: Eighty nCR-SAC were compared with clinical and nonclinical groups of nonabused children matched by age, race, and socioeconomic status. Structured and semistructured interviews and standardized rating scales were used for assessment. RESULTS: More posttraumatic stress disorder (PTSD) was found in the nCR-SAC than in the two comparison groups, and symptom severity was intermediate, except for symptoms of posttraumatic stress, trait anxiety, and depression, which were highest in the nCR-SAC. CONCLUSIONS: Sexually abused children are at high risk for PTSD and symptoms of posttraumatic stress, anxiety, and depression in the immediate period after disclosure and termination of abuse. Findings indicate the need for routine and systematic evaluation for these symptoms and PTSD for treatment planning.

Mathematics anxiety and working memory: support for the existence of a deficient inhibition mechanism.

A current theory of anxiety effects in cognition claims that anxiety disrupts normal processing within the working memory system. We examined this theory in the context of a reading task, for participants who were high or low in assessed mathematics anxiety. The task was designed to measure the ability to inhibit attention to distracting information and the effects of this ability on explicit memory performance. The results suggested that math-anxious individuals have a deficient inhibition mechanism whereby working memory resources are consumed by task-irrelevant distracters. A consequence of this deficiency was that explicit memory performance was poorer for high-anxious individuals. Based on these results, the recommendation is made that Eysenck and Calvo's (1992) processing efficiency theory be integrated with Connelly, Hasher, and Zack's (1991) inhibition theory to portray more comprehensively the relation between anxiety and performance.

Why minority group members perceive or do not perceive the discrimination that confronts them: the role of self-esteem and perceived control.

Self-esteem and perceived control were examined to explain why minority group members sometimes perceive discrimination but, more often, minimize the discrimination. Women (Study 1), and Asians and Blacks (Study 2) reacted to negative feedback after information about the probability for discrimination. Minority group members tended to minimize discrimination and attributed their failure to themselves. By perceiving discrimination as a reason for failure, minority group members protected their performance state self-esteem. In contrast, by minimizing discrimination, they protected their social state self-esteem and maintained the perception of control in the performance and social domains. Results suggest that minority group members minimize discrimination because the consequences of doing so are psychologically beneficial.

Experimental cytoxan cystitis and prevention by acetylcysteine.

Cytoxan (cyclophosphamide) given to rats intraperitoneally produced a severe cystitis within four hours with marked inflammatory edema and hemorrhagic ulcerations of the mucosa. An in vivo staining test with methylene blue showed deep staining of the urothelium as has been demonstrated with other types of urothelial injuries; uninjured urothelium does not stain. The cytoxan cystitis is probably not due to cytoxan itself, but to a breakdown product acrolein, an aldehyde appearing in the urine. Rat experiments demonstrated that acrolein instilled intravesically produced a cystitis similar to that found with cytoxan injected intraperitoneally. The cystitis due either to cytoxan or acrolein was prevented by simultaneous intravesical administration of an aldehyde inactivating agent, acetylcysteine (mucomyst).