An ultrasonography-based approach for tissue modelling to inform photo-therapy treatment strategies.

Currently, diagnostic medicine uses a multitude of tools ranging from ionising radiation to histology analysis. With advances in piezoelectric crystal technology, high-frequency ultrasound imaging has developed to achieve comparatively high resolution without the drawbacks of ionising radiation. This research proposes a low-cost, non-invasive and real-time protocol for informing photo-therapy procedures using ultrasound imaging. We combine currently available ultrasound procedures with Monte Carlo methods for assessing light transport and photo-energy deposition in the tissue. The measurements from high-resolution ultrasound scans are used as input for optical simulations. Consequently, this provides a pipeline that will inform medical practitioners for better therapy strategy planning. While validating known inferences of light transport through biological tissue, our results highlight the range of information such as temporal monitoring and energy deposition at varying depths. This process also retains the flexibility of testing various wavelengths for individual-specific geometries and anatomy.

Optical investigation of three-dimensional human skin equivalents: A pilot study.

Human skin equivalents (HSEs) are three-dimensional living models of human skin that are prepared in vitro by seeding cells onto an appropriate scaffold. They recreate the structure and biological behaviour of real skin, allowing the investigation of processes such as keratinocyte differentiation and interactions between the dermal and epidermal layers. However, for wider applications, their optical and mechanical properties should also replicate those of real skin. We therefore conducted a pilot study to investigate the optical properties of HSEs. We compared Monte Carlo simulations of (a) real human skin and (b) two-layer optical models of HSEs with (c) experimental measurements of transmittance through HSE samples. The skin layers were described using a hybrid collection of optical attenuation coefficients. A linear relationship was observed between the simulations and experiments. For samples thinner than 0.5 mm, an exponential increase in detected power was observed due to fewer instances of absorption and scattering.

Do Differences in Learning Performance Precede or Follow Initiation of Marijuana Use?

OBJECTIVE: Studies examining cross-sectional associations between age at marijuana initiation and memory deficits yield mixed results. Because longitudinal data are sparse, controversy continues regarding whether these deficits reflect premorbid risk factors or sequelae of early marijuana initiation; here, we examine this question in a community sample followed since birth. METHOD: Masked examiners administered four subtests of the Wide Range Assessment of Memory and Learning (WRAML/WRAML2) from childhood until young adulthood to 119 urban, predominantly African American participants. Multivariable generalized estimated equation models measured longitudinal trajectories of learning. Participants were grouped as never users (n = 26), later initiators (≥16 years old; n = 31), and earlier initiators of marijuana use (n = 62). RESULTS: Marijuana onset groups did not significantly differ on WRAML scaled scores or IQ in childhood, nor did they differ on WRAML scaled scores in adolescence. On most WRAML2 subtests, these groups did not significantly differ in young adulthood after taking into account sex and childhood IQ. However, on Story Memory, later initiators attained higher scaled scores in young adulthood, even after including additional covariates of anxiety, depression, postsecondary education, past-month marijuana use, and past-week high-risk drinking. They showed a significantly more positive trajectory than never users that was driven by within-group improvement after adolescence. Earlier initiators showed within-group decline in Story Memory after adolescence. CONCLUSIONS: Differences in learning following earlier initiation of marijuana use may not be solely attributable to premorbid deficits.

Childhood Trauma Questionnaire (CTQ) correlations with prospective violence assessment in a longitudinal cohort.

Retrospective recall-based measures administered to adults, like the Childhood Trauma Questionnaire (CTQ), are commonly used to determine experiences of childhood trauma in the home. However, the CTQ has not been compared with prospective measures of childhood violence exposure, whether at home or in the community. We evaluated the relationships between young adults' responses to the CTQ and their prospective self-reports of exposure to violence in childhood and adolescence. Participants were 127 (93% African American, 47% male) urban young adults in a longitudinal birth cohort study examining effects of prenatal substance exposure and environmental factors on development. Participants completed the Violence Exposure Scale for Children-Revised (VEX-R), a 21-item self-report measure of experience of/witness to interpersonal violence, administered face to face at 9, 10, and 11 years using cartoon pictures, and via audio-computer assisted self-interview at 12, 14, and 16 years. Participants also completed the CTQ, a 28-item, 5-scale screening measure, during a young-adult follow-up (ages 18-23). Using Pearson Correlation coefficients, VEX-R total scores significantly correlated with the sum of CTQ scales, r = .33, p < .01, and 3 (physical, emotional, and sexual abuse) of the 5 CTQ subscales, showing a moderate linear association. This study suggests that the CTQ serves as a reasonable retrospective assessment of prospectively ascertained childhood trauma exposure. The differences may be accounted for by disparities in domains assessed. (PsycINFO Database Record

HIV Risk, Substance Use, and Personality Characteristics among Adults with History of Serious Mental Illness.

The present study examined the relationship between characteristics associated with personality disorders, substance use, and HIV risk among adults with a history of serious mental illness. Participants included 103 adults with antisocial or borderline personality disorder, serious mental illness, and recent HIV risk behavior. The sample was predominately male (64%), diverse (42% African American and 13% Hispanic), and homeless/marginally housed (76%). In order to examine the relationship between personality characteristics and risk we constructed a risk index comprising key symptoms of antisocial and borderline personality disorders, namely; impulsivity, affective instability, and disregard for safety of self/others. Contrary to our primary hypotheses, risk index scores did not predict HIV risk behavior and substance abuse did not mediate this risk. Exploratory analyses did reveal that women engaged in significantly more risk behaviors than their male counterparts and that risk scores were a significant predictor of total sex acts for women but not men. In addition, increased emotional dysregulation was a significant predictor of condomless sex acts for women but not men. Finally, recent alcohol use and increased impulsivity was associated with more condomless oral sex for men and women. These results suggest the relationship among serious mental illness, personality disorder, substance abuse, and gender is complex and merits further study.

Intrauterine exposure to tobacco and executive functioning in high school.

BACKGROUND: Executive functioning (EF), an umbrella construct encompassing gradual maturation of cognitive organization/management processes, is important to success in multiple settings including high school. Intrauterine tobacco exposure (IUTE) correlates with negative cognitive/behavioral outcomes, but little is known about its association with adolescent EF and information from real-life contexts is sparse. We evaluated the impact of IUTE on teacher-reported observations of EF in urban high school students controlling for covariates including other intrauterine and adolescent substance exposures. METHODS: A prospective low-income birth cohort (51% male; 89% African American/Caribbean) was followed through late adolescence (16-18 years old). At birth, intrauterine exposures to cocaine and other substances (52% cocaine, 52% tobacco, 26% marijuana, 26% alcohol) were identified by meconium and/or urine assays, and/or maternal self-report. High school teachers knowledgeable about the student and unaware of study aims were asked to complete the Behavior Rating Inventory of Executive Functioning-Teacher Form (BRIEF-TF) annually. RESULTS: Teachers completed at least one BRIEF-TF for 131 adolescents. Multivariable analyses included controls for: demographics; intrauterine cocaine, marijuana, and alcohol exposures; early childhood exposures to lead; and violence exposure from school-age to adolescence. IUTE was associated with less optimal BRIEF-TF Behavioral Regulation scores (p <0.05). Other intrauterine substance exposures did not predict less optimal BRIEF-TF scores, nor did exposures to violence, lead, nor adolescents' own substance use. CONCLUSIONS: IUTE is associated with offspring's less optimal EF. Prenatal counseling should emphasize abstinence from tobacco, as well as alcohol and illegal substances.

Prenatal, perinatal, and adolescent exposure to marijuana: Relationships with aggressive behavior.

This manuscript reviews research exploring the relationship between prenatal, perinatal, and adolescent exposure to marijuana and aggressive behavior, including physical aggression. Areas of inquiry include animal research, as well as human research, on prenatal exposure and on marijuana use during adolescence. Potential psychosocial and psychopharmacological mechanisms are identified, as well as relevant confounds. The prenatal marijuana exposure literature provides minimal support for a direct relationship with aggressive behavior in childhood. The adolescent use literature suggests a marginal (at best) association between acute intoxication and aggressive behavior, and an association between chronic use and aggressive behavior heavily influenced by demographic variables, rather than direct, psychopharmacological mechanisms. Cannabis withdrawal symptoms also may include aggression and anger, but there is little evidence to suggest that these effects are large or specific to withdrawal from marijuana compared to other substances. This review will offer recommendations for clinical care and public policy, as well as important questions for future research.

Psychological Distress Among School-Aged Children with and Without Intrauterine Cocaine Exposure: Perinatal Versus Contextual Effects.

Whether intrauterine cocaine exposure (IUCE) explains unique variance in psychiatric functioning among school age children, even after controlling for other biological and social risk factors, has not been fully delineated. As part of a longitudinal birth cohort study of children with and without IUCE, we conducted and analyzed data based on structured clinical interviews with 105 children (57% male) and their caregivers when the child was approximately 8.5 years old; 47% of the children had experienced IUCE. Interviews included past and current major psychological disorders and sub-threshold mental health symptoms. Potential covariates were ascertained by interviews of birth mothers and other caregivers from shortly after the child's birth until the 8.5-year visit. More than one-third of children met DSM-IV criteria for one or more mood, anxiety, attention deficit, or disruptive behavior disorders. IUCE was not significantly associated with children's history of psychological distress, in either bivariate or multiple logistic regressions. In contrast, birth mothers' acknowledgement of greater psychiatric distress at baseline and higher levels of alcohol consumption during pregnancy, and at 8.5 years caregivers' reports of their own psychological distress, and children's lower IQ were predictors of higher rates of psychological morbidity. Findings are consistent with prior reports suggesting that, regardless of IUCE status, children from low-income, urban backgrounds are at heightened risk for psychological distress. Results underscore the need for closer monitoring of the mental health of children living in low-income households, with or without intrauterine substance exposures, to facilitate access to appropriate services.

Effects of intrauterine substance and postnatal violence exposure on aggression in children.

During the cocaine epidemic of the 1980s and early 1990s, many expressed fears that children with intrauterine cocaine exposure (IUCE) would grow up to be unusually violent. The present study examines the relationship of caregiver reports of school-age children's aggressive behavior with IUCE and postnatal exposure to violence. Respondents were 140 low-income, primarily African American children, ages 8-11, and each child's current primary caregiver from a longitudinal study evaluating potential long term sequelae of IUCE. Multiple regression analyses were used to investigate the independent and interactive effects of level of IUCE (None (n = 69), Lighter (n = 47), Heavier (n = 24)) and exposure to violence (Violence Exposure Scale for Children-Revised) on aggressive behavior (Child Behavior Checklist), while also controlling for other intrauterine substance exposures and additional contextual factors. Children's self-reported exposure to violence was significantly positively associated with caregivers' reports of aggressive behavior (ß = 2.17, P = .05), as was concurrent caregiver's psychiatric distress (ß = .15, P = .003). However, neither IUCE nor its interaction with exposure to violence showed a significant association with aggressive behavior. Findings suggest the importance of postnatal social environment rather than IUCE in predicting aggressive behavior in childhood.

A Novel Image Representation via Local Frequency Analysis for Illumination Invariant Stereo Matching.

In this paper, we propose a novel image representation approach to tackle illumination variations in stereo matching problems. Images are mapped using their Fourier transforms which are convolved with a set of monogenic filters. Frequency analysis is carried out at different scales to account for most image content. The phase congruency and the local weighted mean phase angle are then computed over all the scales. The original image is transformed into a new representation using these two mappings. This representation is invariant to illumination and contrast variations. More importantly, it is generic and can be used with most sparse as well as dense stereo matching algorithms. In addition, sequential feature matching or tracking can also benefit from our approach in varying radiometric conditions. We demonstrate the improvements introduced with our image mappings on well-established data sets in the literature as well as on our own experimental scenarios that include high dynamic range imagery. The experiments include both dense and sparse stereo and sequential matching algorithms where the latter is considered in the very challenging visual odometry framework.

Zonisamide, topiramate, and levetiracetam: efficacy and neuropsychological effects in alcohol use disorders.

The anticonvulsant topiramate not only decreases ethanol consumption in alcohol dependence (AD) but also may produce several adverse events including cognitive impairment. Zonisamide is a structurally related anticonvulsant that is a promising agent for the treatment of AD and may have greater tolerability than topiramate. This study evaluated the effects of zonisamide (400 mg/d) on alcohol consumption and its neurotoxic effects in subjects with AD. A double-blind placebo-controlled clinical trial was conducted using 2 comparator anticonvulsant drugs, topiramate (300 mg/d) and levetiracetam (2000 mg/d), which does not impair cognition. Study medications were administered for 14 weeks, including a 2-week taper period. Medication adherence was facilitated using Brief Behavioral Compliance Enhancement Treatment. The neurotoxicity of the study drugs was assessed using neuropsychological tests and the AB-Neurotoxicity Scale. Compared with placebo, both zonisamide and topiramate produced significant reductions in the drinks consumed per day, percent days drinking, and percent days heavy drinking. Only the percent days heavy drinking was significantly decreased in the levetiracetam group. The topiramate cell was the only group that had a significant increase on the mental slowing subscale of the Neurotoxicity Scale compared with placebo at study weeks 11 and 12. Topiramate and zonisamide both produced modest reductions in verbal fluency and working memory. These findings indicate that zonisamide may have efficacy in the treatment of AD, with effect sizes similar to topiramate. Both of these drugs produced similar patterns of cognitive impairment, although only the topiramate group reported significant increases in mental slowing.

Early adolescent executive functioning, intrauterine exposures and own drug use.

Individual differences in adolescents' executive functioning are often attributed either to intrauterine substance exposure or to adolescents' own substance use, but both predictors typically have not been evaluated simultaneously in the same study. This prospective study evaluated whether intrauterine drug exposures, the adolescents' own substance use, and/or their potential interactions are related to poorer executive functioning after controlling for important contextual variables. Analyses were based on data collected on a sample of 137 predominantly African-American/African Caribbean adolescents from low-income urban backgrounds who were followed since their term birth. Intrauterine substance exposures (cocaine, marijuana, alcohol, and cigarettes) and adolescents' substance use were documented using a combination of biological assays and maternal and adolescent self-report. At 12-14 years of age, examiners masked to intrauterine exposures and current substance use assessed the adolescents using the Delis-Kaplan Executive Function System (D-KEFS), an age-referenced instrument evaluating multiple dimensions of executive functioning (EF). Results of covariate-controlled analyses in this study suggest that when intrauterine substance exposures and young adolescents' substance use variables were in the same analysis models, subtle differences in specific EF outcomes were identifiable in this non-referred sample. While further study with larger samples is indicated, these findings suggest that 1) research on adolescent substance use and intrauterine exposure research should evaluate both predictors simultaneously, 2) subtle neurocognitive effects associated with specific intrauterine drug exposures can be identified during early adolescence, and 3) intrauterine substance exposure effects may differ from those associated with adolescents' own drug use.

Open label trial of the tolerability and efficacy of zonisamide in the treatment of alcohol dependence.

OBJECTIVES: The objectives of this study are to assess the tolerability and efficacy of the anticonvulsant zonisamide in an open label trial of the treatment of alcohol dependence. METHODS: In this trial, zonisamide (400-mg daily) was administered to alcohol-dependent subjects (ADS) (n = 16) over 13 weeks. The mean daily consumption of standard alcoholic drinks and performance on a verbal fluency task, the COWAT, and on a measure of attention and visuomotor speed, the DSMT were assessed, and the occurrence of adverse events was monitored weekly. RESULTS: The mean number of drinks consumed daily was significantly reduced from baseline levels during the treatment period. Performances on the COWAT and on the DSMT were not significantly reduced by zonisamide treatment. Overall, zonisamide was well tolerated by the study subjects. CONCLUSION: These results indicate that zonisamide administration may not impair verbal fluency in ADS, and are consistent with other studies that found zonisamide administration may reduce alcohol intake.

Contributors to neuropsychological impairment in HIV-infected and HIV-uninfected opiate-dependent patients.

Neuropsychological (NP) impairment is multiply determined among HIV-infected and HIV-uninfected individuals who are also dually diagnosed with depression and who use illicit substances. The purpose of the present study was to assess the impact of HIV status, depression, and problematic substance use on NP performance. A total of 160 opiate-dependent outpatients undergoing methadone maintenance (80 HIV-infected, 80 HIV-uninfected) completed diagnostic and NP evaluations. Raw scores from individual NP tests were converted to Z scores relative to standard norms and were averaged to form a composite score. HIV-infected participants had significantly lower overall NP performance--as well as lower performance on tests of attention, motor speed, and verbal memory--than HIV-uninfected participants. In multiple regression analyses considering the role of depression and substance use, only HIV status emerged as a significant predictor of NP impairment. These findings confirm NP impairment in HIV-infected substance abusing patients independent of comorbid depression and severity of substance use.

The anticonvulsant zonisamide reduces ethanol self-administration by risky drinkers.

OBJECTIVE: The purpose of this study is to examine the effects of zonisamide on ethanol self-administration and subjective effects in risky drinkers using a human laboratory paradigm. METHOD: We conducted a double-blind, placebo-controlled study of the effects of zonisamide 100 mg on ethanol self-administration and urge to drink in risky drinkers (N = 10) ( [1] ). RESULT: During the second hour of a 2-hour self-administration session ethanol consumption was 50% lower in the zonisamide group as compared to the placebo group. Urge to drink was also significantly lower under the zonisamide condition. CONCLUSION: These results indicate that a single dose of zonisamide reduces urge to drink and the quantity of ethanol self-administered by risky drinkers during their second hour of access to alcohol. SCIENTIFIC SIGNIFICANCE: Zonisamide may help individuals drinking at risky levels reduce their intake of alcohol.

The impact of neuropsychological functioning on adherence to HAART in HIV-infected substance abuse patients.

This study assessed the frequency of neuropsychological impairment and its relationship to adherence in a sample of HIV-infected injection drug users (IDUs) in treatment. One hundred eight participants recruited between September 2006 and October 2008 completed psychodiagnostic and neuropsychological assessments and monitored HAART adherence over a 2-week period via the use of Medication Event Monitoring System (MEMS) electronic pill caps and self-report. Assessment of concurrent functioning included clinician-rated scales of depression and substance use severity, and a battery of neuropsychological tests. Findings from individual neuropsychological tests were converted to Z scores relative to standard norms and averaged to form a composite score (NPZ). NPZ was generally poor (mean = -1.505, standard deviation = 1.120), with 76.9% of the sample being classified as highly impaired. Self-reported adherence was significantly higher than MEMS cap adherence. In contrast with previous studies, overall neuropsychological functioning was not a significant predictor of electronically monitored or self-reported adherence. However, examiner-rated current global severity of substance use and delayed word list recall emerged as significant predictors of self-reported adherence. Additionally, estimated premorbid verbal intelligence emerged as a significant predictor of the discrepancy between electronically monitored and self-reported adherence. Given the extent of neuropsychological impairment in this sample, future studies should examine the degree to which the impact of neuropsychological impairment may moderate interventions for this population, and the extent to which skills to cope with neuropsychological problems may boost the potential efficacy of such interventions.

Distinct functions of activated protein C differentially attenuate acute kidney injury.

Administration of activated protein C (APC) protects from renal dysfunction, but the underlying mechanism is unknown. APC exerts both antithrombotic and cytoprotective properties, the latter via modulation of protease-activated receptor-1 (PAR-1) signaling. We generated APC variants to study the relative importance of the two functions of APC in a model of LPS-induced renal microvascular dysfunction. Compared with wild-type APC, the K193E variant exhibited impaired anticoagulant activity but retained the ability to mediate PAR-1-dependent signaling. In contrast, the L8W variant retained anticoagulant activity but lost its ability to modulate PAR-1. By administering wild-type APC or these mutants in a rat model of LPS-induced injury, we found that the PAR-1 agonism, but not the anticoagulant function of APC, reversed LPS-induced systemic hypotension. In contrast, both functions of APC played a role in reversing LPS-induced decreases in renal blood flow and volume, although the effects on PAR-1-dependent signaling were more potent. Regarding potential mechanisms for these findings, APC-mediated PAR-1 agonism suppressed LPS-induced increases in the vasoactive peptide adrenomedullin and infiltration of iNOS-positive leukocytes into renal tissue. However, the anticoagulant function of APC was responsible for suppressing LPS-induced stimulation of the proinflammatory mediators ACE-1, IL-6, and IL-18, perhaps accounting for its ability to modulate renal hemodynamics. Both variants reduced active caspase-3 and abrogated LPS-induced renal dysfunction and pathology. We conclude that although PAR-1 agonism is solely responsible for APC-mediated improvement in systemic hemodynamics, both functions of APC play distinct roles in attenuating the response to injury in the kidney.

Gender and other psychosocial factors as predictors of adherence to highly active antiretroviral therapy (HAART) in adults with comorbid HIV/AIDS, psychiatric and substance-related disorder.

This study assessed adherence to HAART among 67 HIV-infected adults, and the degree to which gender and psychological factors-including depression, drug and alcohol use, quality of life, and medication side effects-influenced adherence. Although overall adherence was greater than rates reported in similar studies, no significant difference in adherence was observed between men and women in the present sample. Medication side effects were a significant predictor of non-adherence in the sample at large and among women in particular, while alcohol dependence was a significant predictor of non-adherence only in women. Possible explanations are explored.

Treatment of sepsis-induced acquired protein C deficiency reverses Angiotensin-converting enzyme-2 inhibition and decreases pulmonary inflammatory response.

The protein C (PC) pathway plays an important role in vascular and immune function, and acquired deficiency during sepsis is associated with increased mortality in both animal models and in clinical studies. However, the association of acquired PC deficiency with the pathophysiology of lung injury is unclear. We hypothesized that low PC induced by sepsis would associate with increased pulmonary injury and that replacement with activated protein C (APC) would reverse the activation of pathways associated with injury. Using a cecal ligation and puncture (CLP) model of polymicrobial sepsis, we examined the role of acquired PC deficiency on acute lung injury assessed by analyzing changes in pulmonary pathology, chemokine response, inducible nitric-oxide synthase (iNOS), and the angiotensin pathway. Acquired PC deficiency was strongly associated with an increase in lung inflammation and drivers of pulmonary injury, including angiotensin (Ang) II, thymus and activation-regulated chemokine, plasminogen activator inhibitor (PAI)-1, and iNOS. In contrast, the protective factor angiotensin-converting enzyme (ACE)-2 was significantly suppressed in animals with acquired PC deficiency. The endothelial protein C receptor, required for the cytoprotective signaling of APC, was significantly increased post-CLP, suggesting a compensatory up-regulation of the signaling receptor. Treatment of septic animals with APC reduced pulmonary pathology, suppressed the macrophage inflammatory protein family chemokine response, iNOS expression, and PAI-1 activity and up-regulated ACE-2 expression with concomitant reduction in AngII peptide. These data demonstrate a clear link between acquired PC deficiency and pulmonary inflammatory response in the rat sepsis model and provide support for the concept of APC as a replacement therapy in acute lung injury associated with acquired PC deficiency.