Diffusion MR imaging acquisition and analytics for microstructural delineation in pre-clinical models of TBI.

Significant progress has been made toward improving both the acquisition of clinical diffusion-weighted imaging (DWI) data and its analysis in the uninjured brain, through various techniques including a large number of model-based solutions that have been proposed to fit for multiple tissue compartments, and multiple fibers per voxel. While some of these techniques have been applied to clinical traumatic brain injury (TBI) research, the majority of these technological enhancements have yet to be fully implemented in the preclinical arena of TBI animal model-based research. In this review, we describe the requirement for preclinical, MRI-based efforts to provide systematic confirmation of the applicability of some of these models as indicators of tissue pathology within the injured brain. We review how current DWI techniques are currently being used in animal TBI models, and describe how both acquisition and analytic techniques could be extended to leverage the progress made in clinical work. Finally, we highlight remaining gaps in the preclinical pipeline from data acquisition to final analysis that currently have no real, preclinical-based correlate.

Adhesion and growth of osteoblast-like cells on laser-engineered porous titanium surface: expression and localization of N-cadherin and beta-catenin.

Response of different types of cells on biomaterials is crucial for the applications of tissue engineering and regenerative medicine. It is recognized that cell behaviour depends largely on material surface characteristics. The purpose of this study was to define the biologic response of MG63 cells to the innovative patented surface SYNTHEGRA. MG63 morphology and distribution on the three different titanium disk surfaces (sandblasted, smooth, and laser-treated) were evaluated by microscopy analysis after staining with hematoxylin and eosin. Cell adhesion was determined by crystal violet assay at 48 h while proliferation and cytotoxicity were performed by MTT assay at 24, 48, 72 and 240 h. The expression and localization of N-cadherin and beta-catenin were studied by immunofluorescence and confocal microscopy. At 48 h the adhesion was similar in all titanium surfaces, no difference in cell viability were observed in all titanium disks when compared with controls, while the cell growth on laser-treated disks was significantly higher at 240 h than at 24 and 72 h. Morphological analysis show that cells are aligned along the grooves and inside the cavities. beta-catenin signal appeared more diffuse and localized underneath the cell membrane, while N-cadherin signal was fainter in cells grown on SYNTHEGRA surface. This work put into evidence the performance of newly designed laser-micromachined surface for adhesion, growth and distribution of human osteoblast-like cells. SYNTHEGRA surface inducing modification of N-cadherin and beta-catenin expression and localization, are suggestive of cells undergoing differentiation towards osteocytes and could be particularly suited for immediate load implant procedures.

Early quality of life in patients with localized prostate carcinoma: an examination of treatment-related, demographic, and psychosocial factors.

BACKGROUND: Men with localized prostate carcinoma are faced with important treatment decisions, and quality of life (QoL) information has become a crucial element of decision making. The first objective of this study was to compare the early, health-related QoL (HRQoL) of men with localized prostate carcinoma who were treated with radical prostatectomy, external beam radiotherapy, or brachytherapy. A second objective was to identify demographic and psychosocial variables that predict HRQoL. METHODS: Two-hundred fifty-six men with localized prostate carcinoma were interviewed within 7 weeks of treatment initiation. The interview included measures of prostate-specific HRQoL (the University of California-Los Angeles Prostate Cancer Index), general HRQoL (the SF-36), and psychosocial variables. RESULTS: After adjusting for covariates, treatment group differences were found for both prostate specific HRQoL and general HRQoL. Men who underwent prostatectomy reported more urinary and sexual problems and more general physical dysfunction compared with men who were treated with either form of radiation therapy. Men who were treated with brachytherapy reported the fewest problems in sexual function and the least general physical dysfunction. Few treatment group differences were found in mental functioning. Both demographic factors and psychosocial factors predicted HRQoL. Older men and African-American men reported more physical problems than younger men and Caucasian men, respectively. A supportive social environment, high self-efficacy, and high self-esteem were predictive of better HRQoL. CONCLUSIONS: Shortly after undergoing treatment for localized prostate carcinoma, men who underwent radical prostatectomy, older men, and African-American men are at heightened risk for experiencing prostate-specific and general deficits in HRQoL. Having psychosocial resources from which to draw may enhance HRQoL.

Cross-cultural differences in tolerance for crowding: fact or fiction?

It is widely believed that cultures vary in their tolerance for crowding. There is, however, little evidence to substantiate this belief, coupled with serious shortcomings in the extant literature. Tolerance for crowding has been confused with cultural differences in personal space preferences along with perceived crowding. Furthermore, the few studies that have examined cultural variability in reactions to crowding have compared subgroup correlations, which is not equivalent to a statistical interaction. Although the authors found a statistical interaction indicating that Asian Americans and Latin Americans differ in the way they perceive crowding in comparison to their fellow Anglo-American and African American citizens, all four ethnic groups suffer similar, negative psychological distress sequelae of high-density housing. These results hold independently of household income.

Studies on the synthetic compatibility of aryloxime linkers in the solid-phase synthesis of 3-aminobenzisoxazoles.

Further exploration of the scope of our solid-phase method for the synthesis of 3-aminobenzisoxazoles (using the Kaiser oxime resin 1) is described. The effects of base, leaving group, and solvent on the nucleophilic aromatic substitution based resin-loading reaction are discussed. Representative aryloxime intermediates were subjected to a variety of acidic conditions commonly used in protecting group removal to establish the acid stability profile of this linker. Regioselectivity was evaluated with various di- and trifluorobenzonitriles, which gave single benzisoxazole products after loading and cyclorelease reactions. Substituent effects observed in the course of the acid stability and regioselectivity studies suggest that the nitrile plays a critical role in the oxime hydrolysis mechanism. Finally, to establish the compatibility of the aryloxime linker with a variety of useful on-resin synthetic transformations, functionalized substrates were loaded onto resin 1, and carbon-nitrogen, carbon-oxygen, and carbon-carbon bond-forming reactions were successfully executed.

Talking facilitates cognitive-emotional processes of adaptation to an acute stressor.

The authors examined the influence of talking and the social context of talking on cognitive-emotional processes of adjustment to stressors. Two hundred fifty-six undergraduates viewed a stressful stimulus and were then assigned to a no-talk control condition or 1 of 3 talk conditions: talk alone, talk to a validating confederate, or talk to an invalidating confederate. Two days later, they were reexposed to the stressor. Compared with individuals in the no-talk condition, those in the talk alone and validate conditions had a lower level of intrusive thoughts in the 2-day interim, and they had lower perceived stress when reexposed to the stressor. The effects of talking and validation on perceived stress appeared to be mediated by lowered intrusions. The benefits of talking were diluted when disclosures were invalidated. These findings suggest that talking about acute stressors can facilitate adjustment to stressors through cognitive resolution.

Nonevaluative social support reduces cardiovascular reactivity in young women during acutely stressful performance situations.

We tested whether the presence of a stranger reduces cardiovascular responses during stressful tasks if the evaluation potential of the stranger is minimized and whether cardiovascular responses are affected by the quality of support in a friendship. Undergraduate women performed stressful tasks in one of three conditions: Alone, with a same-sex Stranger, or with a same-sex best Friend. The stranger and friend could not hear participants' responses. Alone women had the greatest increases in SBP and HR while women in the Stranger and Friend conditions did not differ in their responses. In the Friend condition, HR responses were smallest in women who were highly satisfied with the support that they generally received from their friend. We conclude that the presence of a nonevaluative friend or stranger can reduce cardiovascular responses and that the quality of supportive ties modulates the impact of those ties on responses to stress.

Negative emotions and acute physiological responses to stress.

One pathway through which stressors are thought to influence physiology is through their effects on emotion. We used meta-analytic statistical techniques with data from nine studies to test the effects of acute laboratory stressors (speech, star mirror-image tracing, handgrip) on emotional (undifferentiated negative emotion, anger, anxiety) and cardiovascular (CV) response. In all of the studies, participants responded to stressors with both increased CV response and increased negative emotion. Increases in negative emotion were associated with increases in CV response across tasks, however, these associations were small. The range of variance accounted for was between 2% and 12%. Thus, the contribution of negative emotion, as assessed in these studies, to physiological responses to acute laboratory stressors was limited. Although these results raise questions about the role of emotion in mediating stress-elicited physiological responses, the nature of the acute laboratory stress paradigm may contribute to the lack of a strong association.

The role of social and cognitive processes in children's adjustment to community violence.

This study examined associations of community violence exposure and psychological well-being among 99 8-12 year old children (M = 10.7 years) using home interviews with mothers and children. Both moderators and mediators of the links between violence exposure and well-being were tested. After demographics and concurrent life stressors were controlled for violence exposure was significantly associated with intrusive thinking, anxiety, and depression. Regression analyses indicated that intrusive thinking partially mediated associated between violence exposure and internalizing symptoms. Planned comparisons revealed that violence exposure had the strongest effect on well-being among children with low social support or high levels of social strains. Furthermore, children with high levels of intrusive thinking were most likely to show heightened internalizing symptoms when they had inadequate social support.

Problems and prospects for the social support-reactivity hypothesis.

Social support and integration have been linked to health and longevity in many correlational studies. To explain how social relationships might enhance health, investigators are examining the effects of social support on physiological processes implicated in disease. Much of this research focuses on testing the social support-reactivity hypothesis, which maintains that social support enhances health by reducing psychobiologic reactivity to stressors. This article identifies the basic assumptions, problems, and prospects of this research endeavor. The major problems discussed include: (a) inconsistent findings across studies; (b) unidentified cognitive and emotional mediators; (c) individual differences in response to social support; and (d) a lack of experimental studies on the role of social support in adjustment to chronic stress. Besides raising consciousness about these problems, I offer ideas for advancing research in this area.

Chronic residential crowding and children's well-being: an ecological perspective.

Chronic residential crowding is associated with difficulties in behavioral adjustment at school, poor academic achievement, heightened vulnerability to the induction of learned helplessness, elevated blood pressure, and impaired parent-child interpersonal relationships among a sample of working-class, 10-to 12-year-old children living in urban India. The significant main effects of residential crowding on blood pressure and learned helplessness are moderated by gender. Residential crowding is positively associated with blood pressure only among boys and with helplessness only among girls. All analyses statistically control for household income. We then demonstrate that perceived parent-child conflict functions as an underlying, intervening process that largely accounts for several correlates of household crowding among children.

Expressive writing moderates the relation between intrusive thoughts and depressive symptoms.

The author investigated whether expressive writing enhances emotional adaptation to a stressful event (graduate entrance exams) by reducing event-related intrusive thoughts or by desensitizing people to such thoughts. Participants in the experimental group, who were instructed to write their deepest thoughts and feelings about the exam, exhibited a significant decline in depressive symptoms from 1 month (Time 1) to 3 days (Time 2) before the exam. Participants in the control group, who wrote about a trivial topic, maintained a relatively high level of depressive symptoms over this same period. Expressive writing did not affect the frequency of intrusive thoughts, but it moderated the impact of intrusive thoughts on depressive symptoms. Specifically, intrusive thoughts at Time 1 were positively related to depressive symptoms at Time 2 in the control group and were unrelated to symptoms in the expressive writing group.

Relation of chronic and episodic stressors to psychological distress, reactivity, and health.

This study tested the hypothesis that exposure to chronic stressors, which reflect persistent, negative life situations, would have greater physiological, psychological, and physical health costs than exposure to episodic or intermediate-length stressors, which reflect relatively transient, negative life situations. We also tested whether cardiovascular reactivity, conceptualized as a marker of underlying pathophysiological states, would mediate the relation between chronic stress and psychological distress and illness. Participants were 75 male and 75 female college students. Compared with students experiencing few chronic life stressors, students experiencing many chronic life stressors had exaggerated cardiovascular responses to acute challenges, delayed recovery to resting levels of cardiovascular functioning after the acute challenges, elevated psychological distress levels, and they reported more illnesses. None of the outcomes was associated with the number of episodic or intermediate-length life stressors students experienced. Cardiovascular reactivity did not mediate the stress-distress or stress-illness associations. The results suggest that ongoing stressors that are static are more detrimental to health and well-being than are episodic of change-related stressors.

Long-term Treatment With Pravastatin Alone and in Combination With Gemfibrozil in Familial Type IIB Hyperlipoproteinemia or Combined Hyperlipidemia.

BACKGROUND: Pravastatin inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase. It prevents mevalonate synthesis, reducing endogenous cholesterol production, and reduces cholesterol content in the liver, thus resulting in a down-regulation of low-density lipoprotein receptor production. Gemfibrozil reduces very low-density lipoprotein production and low-density lipoprotein-cholesterol level and increases very low-density lipoprotein catabolism. Therefore, it was suggested that combination therapy with both drugs could effect greater reduction of cholesterol levels as compared to pravastatin alone. The present study was carried out to evaluate the efficacy and safety of pravastatin as a monotherapy or in combination with gemfibrozil in the treatment of patients with familial type IIb hyperlipoproteinemia or familial combined hyperlipidemia. METHODS AND RESULTS: Forty-one patients were included in the study. All patients initially followed 6 weeks of hypolipidemic diet; subsequently they were randomized and received either 20 mg once daily of pravastatin alone (n = 13) or 20 mg of pravastatin together with 600 mg of gemfibrozil twice daily (n = 14). As a control, 14 patients were treated with diet only. The treatment lasted 24 months and clinical evaluation and laboratory tests were done at given time points. Both groups of treated patients showed an early reduction (3 months) of total (about 30% P <.01 vs controls), low-density lipoprotein (about 35%, P <.01 vs controls) and very low-density lipoprotein cholesterol levels (about 18%, P = NS). In contrast, high-density lipoprotein cholesterol levels increased significantly in patients treated with pravastatin and gemfibrozil (about 20%, P <.05 vs controls). Pravastatin treatment alone reduced the level of serum triglycerides as efficiently as in combination with gemfibrozil. Data showed a sustained normalization of lipid profile until 24 months. However, this effect was achieved in patients that had rather low levels of triglycerides. During the treatment we did not observe any difference in the incidence of possible drug-related side effects. Severe myopathy or rhabdomyolysis was not observed at the doses of the drugs used in our study. CONCLUSIONS: Therapy with pravastatin and in combination with gemfibrozil resulted in significant and sustained normalization of lipid profile in high-risk patients with familial type IIb hyperlipoproteinemia or familial combined hyperlipidemia.

Social constraints, intrusive thoughts, and depressive symptoms among bereaved mothers.

The study examined how social constraints on discussion of a traumatic experience can interfere with cognitive processing of and recovery from loss. Bereaved mothers were interviewed at 3 weeks (T1), 3 months (T2), and 18 months (T3) after their infants' death. Intrusive thoughts at T1, conceptualized as a marker of cognitive processing, were negatively associated with talking about infant's death at T2 and T3 among socially constrained mothers. The reverse associations were found among unconstrained mothers. Controlling for initial level of distress, there was a positive relation between T1 intrusive thoughts and depressive symptoms over time among socially constrained mothers. However, higher levels of T1 intrusive thoughts were associated with a decrease in T3 depressive symptoms among mothers with unconstrained social relationships.

Cynicism, social support, and cardiovascular reactivity.

This study examined whether highly cynical individuals benefit less from social support during an acute stressor than individuals low in cynicism. College students (52 men, 52 women) performed a stressful speech task alone or in the presence of a supportive confederate. There was an interactive effect of social support and cynicism on cardiovascular reactivity: Low cynicism participants who received support has smaller increases in blood pressure during the speech than low cynicism participants without support and high cynicism participants with or without support. Participants' psychological stress appeared to mediate the main effects of support on blood pressure reactivity, but not the Support x Cynicism interaction. Results suggest that cynical attitudes may undermine the stress buffering potential of interpersonal support.

Osteoid osteoma of the clavicle.

We describe a case of osteoid osteoma of the clavicle in an Olympic free-style wrestler who presented to us with persistent and increasingly elevated pain in his right shoulder. Originally a persistent injury was considered to be causing the pain, however, the correct diagnosis was made three months after the onset of the symptoms. Even in sportsman where muscle pain is commonplace, non-traumatic conditions should be considered in the presence of persistent and increasingly elevated pain that is not relieved by rest and physiotherapy.

Distorting children's reports and interpretations of events through suggestion.

Fifty-four children (33 girls and 21 boys), 4 to 6 years old, participated in an experiment examining the effects of leading interviews on their interpretations and factual recall of an interaction with a teaching assistant (TA). Children were either familiar or unfamiliar with the TA and were interviewed in either an incriminating or a neutral manner. In comparison with neutral-interview children, incriminating-interview children made more cued-recall errors and endorsed more biased interpretations of the TA's actions. Familiarity with the TA had limited effects on free recall and interpretations of the TA's actions and had no effect on cued recall. Results indicated that 4- to 6-year-olds will produce misleading reports about their interactions with either familiar or unfamiliar adults when they are prompted to do by an opinionated adult interviewer.

Social support lowers cardiovascular reactivity to an acute stressor.

This study examined whether social support can reduce cardiovascular reactivity to an acute stressor. College students gave a speech in one of three social conditions: alone, in the presence of a supportive confederate, or in the presence of a nonsupportive confederate. Systolic and diastolic blood pressure were measured at rest, before the speech, and during the speech. While anticipating and delivering their speech, supported and alone subjects exhibited significantly smaller increases in systolic and diastolic blood pressures than did nonsupported subjects. Supported subjects also exhibited significantly smaller increases in systolic blood pressure than did alone subjects before and during the speech. Men had higher stress-related increases in blood pressures than did women; but gender did not moderate the effects of social support on cardiovascular reactivity. These results provide experimental evidence of potential health benefits of social support during acute stressors.