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1.  Practice Effect and Normative Data of an HIV-specific Neuropsychological Testing Battery among Healthy Thais 
Objective
A longitudinal cohort study was conducted in Bangkok, Thailand between 2008 and 2013 in order to determine the practice effect of serial neuropsychological testing and establish normative data among normal (HIV-uninfected) Thai volunteers.
Material and Method
The authors enrolled 511 cognitively healthy individuals (HIV-uninfected, no drug abuse or other previous/current neurological or psychological conditions) to assess baseline performance on a HIV-specific neuropsychological testing battery. Ninety-nine subjects were re-assessed at 6 and 12 months to evaluate practice effects.
Results
The mean age of the 99 subjects completing longitudinal visits was 49.2 years and 53 were male. The authors identified improved mean raw scores on most neuropsychological tests with repeated measurements; however, only change in WHO Auditory Verbal Learning Test (AVLT) scores (learning, attention, immediate and delayed recall tasks) met statistical significance, with larger differences seen between baseline and 6-month compared to 6 and 12 months follow-up. Older age correlated with poorer baseline raw score, and was a predictor of worse performance at 6 months and 12 months on several tasks. Level of education was associated with practice effects on several tests. No similar effects were observed with gender.
Conclusion
The authors identified improved performance after repeated measurements revealing a significant practice effect on an HIV-specific neuropsychological testing battery employed in Bangkok, Thailand. Main predictors were age and educational attainment.
PMCID: PMC4324973  PMID: 25518198
Thailand; neuropsychological test; cognition
2.  Impact of human immunodeficiency virus on neurocognition and risky behaviors in young adults 
Journal of neurovirology  2014;20(5):466-473.
Previous studies have identified cognitive impairments due to human immunodeficiency virus (HIV) in adults. However, few studies have examined the impact of HIV on cognition in young adults (18-24 years old). Yet, this group is one of the largest populations of individuals with new HIV infection. Young adulthood is also an important developmental window as the brain has not fully matured and individuals are prone to engage in risky behavior. The purpose of the present study was to examine the impact of HIV on neurocognition and risky behaviors. We hypothesized that HIV+ young adults (n=23) would exhibit greater cognitive impairment and risky behaviors compared to seronegative controls (n=21). In addition, we predicted that self-reported risky behavior as assessed by the Risk Assessment Battery (RAB) would covary with cognitive performances. Results revealed poorer executive function in HIV+ young adults compared to seronegative controls. HIV+ young adults also exhibited significantly greater risk scores on the RAB (p < 0.01) compared to HIV- young adults. However, there were no relationships between risky behavior and cognitive performance. Overall, our results suggest that HIV is associated with poorer cognition and increased risky behaviors in young adults.
doi:10.1007/s13365-014-0264-4
PMCID: PMC4305333  PMID: 24970235
HIV; Cognition; Risky Behavior; Neuropsychology; Executive Function
4.  Young Men’s Shame about Their Desire for other Men Predicts Risky Sex and Moderates the Knowledge – Self-Efficacy Link 
Background: Nationally, HIV incidence is rising rapidly among young (18–24 years old) men who have sex with men (YMSM). Knowledge of safer sex generally enhances self-efficacy for safer sex, an important predictor of safer-sex behaviors. Recent findings suggest that a strong negative social emotion (i.e., shame) increases YMSM’s sexual risk-taking. Unchangeable shame (e.g., desire for other men) might undermine (moderate) the link between knowledge and self-efficacy or between self-efficacy and unprotected anal intercourse (UAI): this may be less likely for changeable shame (e.g., shame about risky sexual behavior).
Aim: To test the hypotheses that shame (i.e., sexual desire shame), but not shame about behavior (i.e., sexual behavior shame), will be positively related to UAI and will moderate the relationship between knowledge and self-efficacy and/or self-efficacy and UAI among YMSM.
Method: In an online national study, 1177 young adult (18–24 years old) MSM reported one or more acts of UAI in the past 90 days with a casual partner. Eligible MSM filled out a survey in which they provided information about their knowledge of safer sex, self-efficacy for safer sex, reported levels of shame, and reported past 90-day UAI.
Results: Sexual desire shame was negatively correlated with knowledge and self-efficacy and positively correlated with UAI, the pattern reversed for sexual behavior shame. Sexual desire shame significantly lowered the knowledge to self-efficacy and the self-efficacy to UAI links. Sexual behavior shame also reduced the link from knowledge to self-efficacy, but not the self-efficacy to UAI link.
Conclusion: The present study shows that there are different types of shame that may produce different effects with different implications for health behavior. Sexual desire shame may better reflect an emotion that is activated prior to risky behavior (e.g., when men reflect upon or feel desire for another man). Sexual behavior shame, on the other hand, better reflects what has already happened, thus, those higher in knowledge, efficacy, and therefore, safer sex are least likely to experience shame behavior.
doi:10.3389/fpubh.2014.00183
PMCID: PMC4202720  PMID: 25368860
young MSM; young adult; shame; self-efficacy; safe sex; sex behaviors; safe-sex knowledge; HIV/AIDS
5.  Bariatric Surgery Patients Exhibit Improved Memory Function 12 Months Post-Operatively 
Obesity surgery  2013;23(10):1527-1535.
Introduction/Purpose
Previous work from our group demonstrated improved memory function in bariatric surgery patients at 12 weeks post-operatively relative to controls. However, no study has examined longer term changes in cognitive functioning following bariatric surgery.
Materials and Methods
A total of 137 individuals (95 bariatric surgery patients, 42 obese controls) were followed prospectively to determine whether post-surgery cognitive improvements persist. Potential mechanisms of change were also examined. Bariatric surgery participants completed self-report measurements and a computerized cognitive test battery prior to surgery and at 12-week and 12-month follow-up; obese controls completed measures at equivalent time points.
Results
Bariatric surgery patients exhibited cognitive deficits relative to well established standardized normative data prior to surgery, and obese controls demonstrated similar deficits. Analyses of longitudinal change indicated an interactive effect on memory indices, with bariatric surgery patients demonstrating better performance post-operatively than obese controls.
Conclusion
While memory performance was improved 12 months post-bariatric surgery, the mechanisms underlying these improvements were unclear and did not appear attributable to obvious post-surgical changes, such as reductions in BMI or co-morbid medical conditions. Future studies employing neuroimaging, metabolic biomarkers, and more precise physiological measurements are needed to determine the mechanisms underlying memory improvements following bariatric surgery.
doi:10.1007/s11695-013-0970-7
PMCID: PMC3773052  PMID: 23636994
obesity; cognitive function; bariatric surgery; longitudinal assessment
6.  HIV Clades B and C are Associated With Reduced Brain Volumetrics 
Journal of neurovirology  2013;19(5):10.1007/s13365-013-0202-x.
Objective
HIV has multiple genetic clades with varying prevalence throughout the world. Both HIV-clade C (HIV-C) and HIV-clade B (HIV-B) can cause cognitive impairment but it is unclear if these clades are characterized by similar patterns of brain dysfunction. We examined brain volumetrics and neuropsychological performance among highly active anti-retroviral therapy (HAART) naïve HIV-B and HIV-C participants.
Design
Thirty-four HAART-naïve HIV-infected (HIV+) participants [(17 HIV-B (United States); 17 HIV-C (South Africa)] and 34 age and education-matched HIV-uninfected (HIV−) participants were evaluated.
Methods
All participants underwent similar laboratory, neuropsychological, and neuroimaging studies. Brain volume measures were assessed within the caudate, putamen, amygdala, thalamus, hippocampus, corpus callosum and cortical (grey and white matter) structures. A linear model that included HIV status, region, and their interaction assessed the effects of the virus on brain volumetrics.
Results
HIV− and HIV+ individuals were similar in age. On laboratory examination, HIV-C participants had lower CD4 cell counts and higher plasma HIV viral loads than HIV-B individuals. In general, HIV+ participants performed significantly worse on neuropsychological measures of processing speed and memory and had significantly smaller relative volumetrics within the thalamus, hippocampus, and corpus callosum and cortical grey and white matter compared to respective HIV− controls. Both HIV-clades B and C are associated with similar volumetric declines when compared to matched HIV− controls.
Conclusions
HIV-B and C were associated with significant reductions in brain volumetrics and poorer neuropsychological performance; however, no specific effect of HIV clade subtype was evident. These findings suggest that HIV-B and HIV-C both detrimentally affect brain integrity.
doi:10.1007/s13365-013-0202-x
PMCID: PMC3845807  PMID: 24078556
HIV clade; brain volumetrics; magnetic resonance imaging; neuropsychological performance
7.  Patient reports of cognitive problems are not associated with neuropsychological test performance in bariatric surgery candidates 
Background
Recent work shows that cognitive deficits are common in bariatric surgery candidates and associated with reduced weight loss at 12 months post-operatively. As pre-operatively neuropsychological assessment is not available for all patients at all sites, many care providers ask patients to self-report their level of cognitive dysfunction. However, the accuracy of patient self-report of cognitive abilities has not been empirically examined.
Setting
Longitudinal Assessment of Bariatric Surgery (LABS), United States; Medical Center
Methods
Eighty-one bariatric surgery candidates completed self-report measures of cognitive functioning and neuropsychological tests of memory and other cognitive abilities.
Results
Analyses found no association between subjective report of cognitive function and objective performance on neuropsychological testing. However, persons with history of major depressive disorder reported experiencing greater cognitive deficits.
Conclusions
These findings suggest that bariatric surgery candidates have little insight into their current level of cognitive function. Future work is needed to confirm these findings and identify brief, objective measures of cognitive function that are sensitive to deficits in bariatric surgery candidates.
doi:10.1016/j.soard.2012.10.008
PMCID: PMC3610809  PMID: 23245496
Bariatric; Cognition; Self-report; Memory; Executive Function
8.  Neuronal fiber bundle lengths in healthy adult carriers of the ApoE4 allele: A quantitative tractography DTI study 
Brain imaging and behavior  2013;7(3):10.1007/s11682-013-9225-4.
The epsilon 4 (e4) isoform of apolipoprotein E (ApoE) is a known genetic risk factor for suboptimal brain health. Morphometry studies of brains with Alzheimer’s disease have reported significant alterations in temporal lobe brain structure of e4 carriers, yet it remains unclear if the presence of an e4 allele is associated with alterations in the microstructure of white matter fiber bundles in healthy populations. The present study used quantitative tractography based on diffusion tensor imaging (qtDTI) to examine the influence of the e4 allele on temporal lobe fiber bundle lengths (FBLs) in 64 healthy older adults with at least one e4 allele (carriers, N=23) versus no e4 allele (non-carriers, N=41). Subtests from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were also analyzed to examine memory performance between groups. Analyses revealed shorter FBLs in the left uncinate fasciculus (UF) (p=.038) of e4 carriers compared to non-carriers. By contrast, neither FBLs specific to the temporal lobe nor memory performances differed significantly between groups. Increased age correlated significantly with shorter FBL in the temporal lobe and UF, and with decreased performance on tests of memory. This is the first study to utilize qtDTI to examine relationships between FBL and ApoE genotype. Results suggest that FBL in the UF is influenced by the presence of an ApoE e4 allele (ApoE4) in healthy older adults. Temporal lobe FBLs, however, are more vulnerable to aging than the presence of an e4 allele.
doi:10.1007/s11682-013-9225-4
PMCID: PMC3726531  PMID: 23475756
ApoE; ApoE4; Tractography; DTI; White matter; Fiber bundle lengths; Aging
9.  Impact of body mass index on neuronal fiber bundle lengths among healthy older adults 
Brain imaging and behavior  2013;7(3):10.1007/s11682-013-9230-7.
Increased body mass index (BMI) has been linked to various detrimental health outcomes, including cognitive dysfunction. Recent work investigating associations between obesity and the brain has revealed decreased white matter microstructural integrity in individuals with elevated BMI, independent of age or comorbid health conditions. However, the relationship between high BMI and white matter fiber bundle length (FBL), which represents a novel metric of microstructural brain integrity, remains unknown. The present study utilized quantitative tractography based on diffusion tensor imaging (DTI) to investigate the relationship between BMI and FBL in 72 otherwise healthy older adults (24 males, 48 females). All participants were between 51 and 85 years of age (M = 63.26, SD = 8.76). Results revealed that elevated BMI was associated with shorter FBL in the temporal lobe, independent of age (p < .01). In addition, increased age was associated with shorter frontal, temporal, and whole brain FBL (all p values < .01). These findings indicate that, while increased age is an important factor associated with reduced FBL, high BMI is uniquely associated with reduced FBL in the temporal lobe. These data offer evidence for additive adverse effects of high BMI on the brain, especially in areas already vulnerable to aging processes and age-related neurodegenerative diseases. Further research is necessary to determine the physiological mechanisms associated with the shortening of FBL in individuals with high BMI.
doi:10.1007/s11682-013-9230-7
PMCID: PMC3830712  PMID: 23564371
Tractography; BMI; DTI; White Matter; Fiber Bundle Length; Aging
10.  Cognitive Function Predicts 24-Month Weight Loss Success Following Bariatric Surgery 
Background
Clinically significant cognitive impairment, particularly in attention/executive and memory function, is found in many patients undergoing bariatric surgery. These difficulties have previously been linked to decreased weight loss 12 months post-surgery, but more protracted examination of this relationship has not yet been conducted.
Objectives
The current study prospectively examined the independent contribution of cognitive function to weight loss 24 months following bariatric surgery. Given the rapid rate of cognitive improvement observed following surgery, postoperative cognitive function (i.e., cognition 12 weeks following surgery, controlling for baseline cognition) was expected to predict lower body mass index (BMI) and higher percent total weight loss (%WL) at 24-month follow-up.
Setting
Data were collected by three sites of the Longitudinal Assessment of Bariatric Surgery (LABS) parent project.
Methods
Fifty-seven individuals enrolled in the LABS project undergoing bariatric surgery completed cognitive evaluation at baseline, 12 weeks, and 24 months. %WL and BMI were calculated for 24-month postoperative follow-up.
Results
Better cognitive function 12 weeks following surgery predicted higher %WL and lower BMI at 24 months, and specific domains of attention/executive and memory function were robustly related to decreased BMI and greater %WL at 24 months.
Conclusions
Results demonstrate that cognitive performance shortly after bariatric surgery predicts greater long-term %WL and lower BMI 24 months following bariatric surgery. Further work is needed to clarify the degree to which this relationship is mediated by adherence to postoperative guidelines.
doi:10.1016/j.soard.2013.04.011
PMCID: PMC3788845  PMID: 23816443
memory; cognition; executive function; adherence
11.  Improved Memory Function Two Years After Bariatric Surgery 
Obesity (Silver Spring, Md.)  2013;22(1):32-38.
Objective
Obesity is as an independent risk factor for poor neurocognitive outcomes, including Alzheimer’s disease. Bariatric surgery has recently been shown to result in improved memory at 12-weeks post-operatively. However, the long-term effects of bariatric surgery on cognitive function remain unclear.
Design and Methods
86 individuals (63 bariatric surgery patients, 23 obese controls) were recruited from a prospective study examining the neurocognitive effects of bariatric surgery. All participants completed self-report measurements and a computerized cognitive test battery prior to surgery and at 12-week and 24-month follow-up; obese controls completed measures at equivalent time points.
Results
Bariatric surgery patients exhibited high rates of pre-operative cognitive impairments in attention, executive function, memory, and language. Relative to obese controls, repeated measures ANOVA showed improvements in memory from baseline to 12-weeks and 24-months post-operatively (p < .05). Regression analyses controlling for baseline factors revealed that a lower BMI at 24-months demonstrated a trend toward significance for improved memory (β = -.30, p = .075).
Conclusion
These findings suggest that cognitive benefits of bariatric surgery may extend to 24-months post-operatively. Larger prospective studies with extended follow-up periods are needed to elucidate whether bariatric surgery decreases risk for cognitive decline and possibly the development of dementia.
doi:10.1002/oby.20494
PMCID: PMC4054602  PMID: 23625587
Obesity; bariatric surgery; cognitive function; weight loss
12.  Cognitive Function Predicts Weight Loss Following Bariatric Surgery 
Background
Clinically significant cognitive impairment is found in a subset of patients undergoing bariatric surgery. These difficulties could contribute to reduced adherence to postsurgical lifestyle changes and decreased weight loss.
Objectives
The current study is the first to prospectively examine the independent contribution of cognitive function to weight loss following bariatric surgery. Executive function/attention and verbal memory at baseline were expected to negatively predict percent excess weight loss (%EWL) and body mass index (BMI) at follow-up.
Setting
Three sites of the Longitudinal Assessment of Bariatric Surgery (LABS) parent project were used: Columbia, Cornell, and Neuropsychiatric Research Institute
Methods
Eighty-four individuals enrolled in the LABS project undergoing bariatric surgery completed cognitive evaluation at baseline. BMI and %EWL were calculated at 12-week and 12-month post-surgery follow-ups.
Results
Clinical impairment in task performance was most prominent in tasks associated with verbal recall and recognition (14.3–15.5% of the sample) and perseverative errors (15.5%). After accounting for demographic and medical variables, baseline tests of attention/executive function and memory predicted BMI and %EWL at 12 months, but not at 12 weeks.
Conclusions
Results demonstrate that baseline cognition predicts greater %EWL and lower BMI 12 months following bariatric surgery. Further work is needed to clarify the degree to which cognition contributes to adherence, and the potential mediation of cognition on the relationship between adherence and weight loss in this group.
doi:10.1016/j.soard.2011.10.008
PMCID: PMC3294182  PMID: 22133580
memory; cognition; executive function
13.  Cognitive Function and Neurodevelopmental Outcomes in HIV-Infected Children Older than 1 Year of Age Randomized to Early Versus Deferred Antiretroviral Therapy: The PREDICT Neurodevelopmental Study 
Background
We previously reported similar AIDS-free survival at 3 years in children who were >1 year old initiating antiretroviral therapy (ART) and randomized to early vs. deferred ART in the PREDICT Study. We now report neurodevelopmental outcomes.
Methods
284 HIV-infected Thai and Cambodian children aged 1–12 years with CD4 counts between 15–24% and no AIDS-defining illness were randomized to initiate ART at enrollment (“early”, n=139) or when CD4 count became <15% or a CDC C event developed (“deferred”, n=145). All underwent age-appropriate neurodevelopment testing including Beery Visual Motor Integration (VMI), Purdue Pegboard, Color Trails and Child Behavioral Checklist (CBCL). Thai children (n=170) also completed Wechsler Intelligence Scale (IQ) and Stanford Binet Memory test. We compared week 144 measures by randomized group and to HIV-uninfected children (n=319).
Results
At week 144, the median age was 9 years and 69 (48%) of the deferred arm children had initiated ART. The early arm had a higher CD4 (33% vs. 24%, p<0.001) and a greater percentage of children with viral suppression (91% vs. 40%, p<0.001). Neurodevelopmental scores did not differ by arm and there were no differences in changes between arms across repeated assessments in time-varying multivariate models. HIV-infected children performed worse than uninfected children on IQ, Beery VMI, Binet memory and CBCL
Conclusions
In HIV-infected children surviving beyond one year of age without ART, neurodevelopmental outcomes were similar with ART initiation at CD4 15–24% vs. < 15%; but both groups performed worse than HIV-uninfected children. The window of opportunity for a positive effect of ART initiation on neurodevelopment may remain in infancy.
doi:10.1097/INF.0b013e31827fb19d
PMCID: PMC3664246  PMID: 23263176
HIV; Children; ART; neurodevelopment; resource-limited settings
14.  Trail Making Test A Improves Performance Characteristics of the International HIV-Dementia Scale to Identify Symptomatic HAND 
Journal of neurovirology  2013;19(2):137-143.
Although HIV-Associated Dementia (HAD) occurs in less than 5% of individuals with access to combination antiretroviral therapy (cART), rates of milder forms of HIV-Associated Neurocognitive Disorder (HAND) are much higher. We sought to define an optimal cut-point for the International HIV-Dementia Scale (IHDS) in Thailand for the identification of symptomatic HAND, defined as both HAD and Mild Neurocognitive Disorder (MND). We then sought to determine if adding a simple test from a larger neuropsychological battery could improve the performance characteristics for identifying symptomatic HAND. In this study 75 seropositive adults in Bangkok, Thailand, subjects completed neuropsychological tests and underwent a full neurological assessment. HAND diagnoses were determined by consensus conference using the 2007 Frascati criteria, blinded to the IHDS results. The optimal IHDS cut-point was determined by Receiver Operating Characteristic analysis with cross-validation. Individual neuropsychological tests were then evaluated and combined with the IHDS to test performance characteristics. The IHDS was poor at detecting symptomatic HAND at the optimized cut-point of ≤10 (sensitivity: 53.3%, specificity: 89.8%). The Trail Making Test A was most effective in improving performance characteristics when combined with the IHDS, with net sensitivity of 86% and specificity of 79%. In this setting, the IHDS performed poorly in identifying symptomatic HAND, but was substantially improved by the addition of Trail Making Test A, which typically requires less than two minutes to complete. This combination should be validated in a larger setting since it may address the critical need for HAND screening instruments in international settings.
doi:10.1007/s13365-013-0151-4
PMCID: PMC3644005  PMID: 23483520
HIV Dementia; Neuropsychology; Asia; Neuropsychological Tests; Trail Making Test
15.  The Alzheimer Disease-8 and Montreal Cognitive Assessment as Screening Tools for Neurocognitive Impairment in HIV-Infected Persons 
Journal of neurovirology  2013;19(1):109-116.
The diagnosis of HIV-associated neurocognitive impairment is time-intensive and often omitted in busy outpatient settings. Brief screening tools are needed. The Montreal Cognitive Assessment (MoCA) and the Alzheimer’s disease (AD)-8 have been used in neurodegenerative disorders. We evaluated the sensitivity and specificity of these brief screening tools in HIV-infected persons. The AD-8, MoCA, and formal neuropsychological testing were administered to 200 HIV-infected patients followed at a single institution. Normalized scores on formal neuropsychological testing were used to define neurocognitive impairment. The sensitivity and specificity of the MoCA and AD-8 were assessed to diagnose impairment. Neurocognitive impairment was highly prevalent in this cohort: 127 persons (64%) were diagnosed with neurocognitive impairment based on formal testing. Using the AD-8 and MoCA, 113 (57%) and 101 (51%) persons were identified with neurocognitive impairment, respectively. The sensitivity and specificity of MoCA were 63% and 71%, respectively. The sensitivity and specificity of AD-8 were 61% and 51%, respectively. Our findings highlight that brief screening tools correlate with formal neuropsychological testing. However, the sensitivities of these screening tools are lower than desired. Nevertheless, given their ease in administration, these tools could assist as a first line for identifying individuals who may subsequently require formal neuropsychological testing.
doi:10.1007/s13365-012-0147-5
PMCID: PMC3655767  PMID: 23345074
HIV; Neurocognitive Disorder; MoCA; AD-8; Neuropsychological Testing; Cognition
17.  Development of normative neuropsychological performance in Thailand for the assessment of HIV-associated neurocognitive disorders 
International studies of HIV-associated neurocognitive disorder (HAND) are needed to determine the viral and host factors associated with cognitive impairment particularly as more than 80% of HIV+ subjects reside in resource-limited settings. Recent diagnostic nomenclature of HAND requires comparison of cognitive performance specifically to local normative data. To evaluate this need for local norms, we compared normative data obtained locally in Thailand to Western norms. The current study examined cognitive performance in 477 seronegative Thai participants (male=211, female=266) who completed a battery of tests sensitive to cognitive changes in HIV. The cohort was divided into three age brackets (20–34; 35–49; 50–65) and four educational levels (no education or primary education, less than secondary certificate, high school/associates degree, Bachelor’s degree or greater). The Thai cohort was compared (using ANCOVA) on a number of measures to a seronegative US cohort (n=236; male=198 female=38) to examine cultural differences in performance. Normative data are provided with age and education stratification. The Thai and US groups performed significantly differently on all neuropsychological measures with the exception of verbal fluency. The Thai group performed better on measures of verbal learning (p<0.001) and memory (p<0.001), and measures of psychomotor speed (p<0.001). Education was a more powerful predictor of performance in the Thai cohort compared to the US group. These results highlight the continued need for the development of normative data within local populations. The use of Western norms as a comparison group could lead to inaccurate identification of HAND in culturally distinct groups.
doi:10.1080/13803395.2012.733682
PMCID: PMC3682786  PMID: 23113809
18.  Early versus deferred antiretroviral therapy for children older than 1 year infected with HIV (PREDICT): a multicentre, randomised, open-label trial 
The Lancet infectious diseases  2012;12(12):933-941.
Summary
Background
The optimum time to start antiretroviral therapy for children diagnosed with HIV infection after 1 year of age is unknown. We assessed whether antiretroviral therapy could be deferred until CD4 percentages declined to less than 15% without affecting AIDS-free survival.
Methods
In our multicentre, randomised, open-label trial at nine research sites in Thailand and Cambodia, we enrolled children aged 1–12 years who were infected with HIV and had CD4 percentages of 15–24%. Participants were randomly assigned (1:1) by a minimisation scheme to start antiretroviral therapy at study entry (early treatment group) or antiretroviral therapy to start when CD4 percentages declined to less than 15% (deferred treatment group). The primary endpoint was AIDS-free survival (based on US Centers for Disease Control and Prevention category C events) at week 144, assessed with the Kaplan-Meier analysis and the log-rank approach. This study is registered with ClinicalTrials.gov, number NCT00234091.
Findings
Between March 28, 2006, and Sept 10, 2008, we enrolled 300 Thai and Cambodian children infected with HIV, with a median age of 6·4 years (IQR 3·9–8·4). 150 children were randomly allocated early antiretroviral therapy (one participant was excluded from analyses after withdrawing before week 0) and 150 children were randomly allocated deferred antiretroviral therapy. Median baseline CD4 percentage was 19% (16–22%). 69 children (46%) in the deferred treatment group started antiretroviral therapy during the study. AIDS-free survival at week 144 in the deferred treatment group was 98·7% (95% CI 94·7–99·7; 148 of 150 patients) compared with 97·9% (93·7–99·3; 146 of 149 patients) in the early treatment group (p=0·6).
Interpretation
AIDS-free survival in both treatment groups was high. This low event rate meant that our study was underpowered to detect differences between treatment start times and thus additional follow-up of study participants or future studies are needed to answer this clinical question.
Funding
US National Institutes of Health, Division of AIDS; National Institute of Allergy and Infectious Diseases; National Institute of Child Health and Human Development; and National Institute of Mental Health.
doi:10.1016/S1473-3099(12)70242-6
PMCID: PMC3541427  PMID: 23059199
19.  Reducing shame in a game that predicts HIV risk reduction for young adult men who have sex with men: a randomized trial delivered nationally over the web 
Journal of the International AIDS Society  2013;16(3Suppl 2):18716.
Introduction
Men who have sex with men (MSM) often face socially sanctioned disapproval of sexual deviance from the heterosexual “normal.” Such sexual stigma can be internalized producing a painful affective state (i.e., shame). Although shame (e.g., addiction) can predict risk-taking (e.g., alcohol abuse), sexual shame's link to sexual risk-taking is unclear. Socially Optimized Learning in Virtual Environments (SOLVE) was designed to reduce MSM's sexual shame, but whether it does so, and if that reduction predicts HIV risk reduction, is unclear. To test if at baseline, MSM's reported past unprotected anal intercourse (UAI) is related to shame; MSM's exposure to SOLVE compared to a wait-list control (WLC) condition reduces MSM's shame; and shame-reduction mediates the link between WLC condition and UAI risk reduction.
Methods
HIV-negative, self-identified African American, Latino or White MSM, aged 18–24 years, who had had UAI with a non-primary/casual partner in the past three months were recruited for a national online study. Eligible MSM were computer randomized to either WLC or a web-delivered SOLVE. Retained MSM completed baseline measures (e.g., UAI in the past three months; current level of shame) and, in the SOLVE group, viewed at least one level of the game. At the end of the first session, shame was measured again. MSM completed follow-up UAI measures three months later. All data from 921 retained MSM (WLC condition, 484; SOLVE condition, 437) were analyzed, with missing data multiply imputed.
Results
At baseline, MSM reporting more risky sexual behaviour reported more shame (r s=0.21; p<0.001). MSM in the SOLVE intervention reported more shame reduction (M=−0.08) than MSM in the control condition (M=0.07; t(919)=4.24; p<0.001). As predicted, the indirect effect was significant (point estimate −0.10, 95% bias-corrected CI [−0.01 to −0.23] such that participants in the SOLVE treatment condition reported greater reductions in shame, which in turn predicted reductions in risky sexual behaviour at follow-up. The direct effect, however, was not significant.
Conclusions
SOLVE is the first intervention to: (1) significantly reduce shame for MSM; and (2) demonstrate that shame-reduction, due to an intervention, is predictive of risk (UAI) reduction over time.
doi:10.7448/IAS.16.3.18716
PMCID: PMC3833191  PMID: 24242264
stigma; shame; intervention; serious games; SOLVE; HIV; AIDS; sexual risk-taking; men who have sex with men (MSM)
20.  A rare presentation of spinal epidural abscess 
BMJ Case Reports  2011;2011:bcr0820114647.
A 77-year-old retired engineer presented to accident and emergency with deteriorating shortness of breath that had been troubling him for several months. At that time, he was being investigated by a chest physician who had identified bilateral diaphragmatic paralysis on ultrasound and was awaiting further imaging. Clinical assessment and nerve conduction studies on this admission were compatible with a diagnosis of motor neuron disease but specialist neurology input recommended an MRI to rule out cord pathology. This proved problematic as the patient was non-invasive ventilation dependent and unable to lay supine as this further compromised his respiratory function. To ensure that a potentially reversible cause for his symptoms was identified, the patient was intubated for an MRI which subsequently demonstrated multi level spinal epidural empyema. The benefits of neurosurgical intervention were judged to be uncertain at best, and following discussion with the family, active care was withdrawn. The patient passed away shortly thereafter.
doi:10.1136/bcr.08.2011.4647
PMCID: PMC3207783  PMID: 22675058
21.  Reduced memory in fat mass and obesity-associated allele carriers among older adults with cardiovascular disease 
Background
Much attention has been paid to the prevalence and predisposition of the fat mass and obesity-associated (FTO) gene to obesity, although only a few studies have characterized the extent to which this affects cognitive function. This study examined differences between risk allele carriers (i.e. FTO-AC/AA) and non-carriers (i.e. FTO-CC) on indices of attention/executive function/psychomotor speed, memory, language, and visual-spatial ability in a sample of older patients with cardiovascular disease.
Methods
We recruited 120 older adults from an outpatient cardiology clinic who underwent blood draw and completed neuropsychological testing. Participants were classified into two groups: one for those who were homozygous for the non-risk-conferring allele (i.e. FTO-CC) (n = 49) and the other for those who had at least one copy of the obesity risk-conferring A allele (i.e. FTO-AC/AA) (n = 71).
Results
Mancova analyses adjusting for age and years of education revealed the FTO-AC/AA group performed significantly worse on indices of memory (λ = 0.94, F(2, 115) = 3.58, P = 0.03, partial η2 = 0.06). Follow-up tests revealed a significant effect for the FTO-AC/AA group, relative to the non-carrier group, on encoding (i.e. California Verbal Learning Test Total Learning) and California Verbal Learning Test long-delay free recall (P < 0.05). No such differences between FTO carriers and non-carriers emerged on tests of attention/executive function/psychomotor speed, language, or visual-spatial ability (P > 0.05 for all).
Conclusions
These findings suggest that the FTO risk allele is associated with reduced memory performance, particularly on aspects of memory encoding and delayed recall. To elucidate underlying mechanisms, these findings will need to be replicated in larger samples that utilize neuroimaging.
doi:10.1111/j.1479-8301.2012.00424.x
PMCID: PMC3806216  PMID: 23551410
cardiovascular disease; cognitive function; FTO risk allele; memory; obesity
22.  Early Exposure to Traumatic Stressors Impairs Emotional Brain Circuitry 
PLoS ONE  2013;8(9):e75524.
Exposure to early life trauma (ELT) is known to have a profound impact on mental development, leading to a higher risk for depression and anxiety. Our aim was to use multiple structural imaging methods to systematically investigate how traumatic stressors early in life impact the emotional brain circuits, typically found impaired with clinical diagnosis of depression and anxiety, across the lifespan in an otherwise healthy cohort. MRI data and self-reported histories of ELT from 352 healthy individuals screened for no psychiatric disorders were analyzed in this study. The volume and cortical thickness of the limbic and cingulate regions were assessed for all participants. A large subset of the cohort also had diffusion tensor imaging data, which was used to quantify white matter structural integrity of these regions. We found a significantly smaller amygdala volume and cortical thickness in the rostral anterior cingulate cortex associated with higher ELT exposure only for the adolescence group. White matter integrity of these regions was not affected. These findings demonstrate that exposure to early life trauma is associated with alterations in the gray matter of cingulate-limbic regions during adolescence in an otherwise healthy sample. These findings are interesting in the context that the affected regions are central neuroanatomical components in the psychopathology of depression, and adolescence is a peak period for risk and onset of the disorder.
doi:10.1371/journal.pone.0075524
PMCID: PMC3779182  PMID: 24073270
23.  Cyclic Peptide Inhibitors of the β-Sliding Clamp in Staphylococcus aureus 
PLoS ONE  2013;8(9):e72273.
Interaction between pairs of Staphylococcus aureus replication proteins was detected in an Escherichia coli based two-hybrid analysis. A reverse two-hybrid system was constructed for selection of compounds that hindered interaction between interacting protein pairs. A number of cyclic peptides, from a library generated by the split intein-mediated circular ligation of peptides and proteins technology, were found to interfere with dimerization of the β-sliding clamp of the replisome. Two 8-mer peptides were analyzed in more detail. Both inhibited DNA replication, led to SOS induction, altered cell morphology and cell death. The peptides were active when added to bacterial cultures indicating that they could traverse the bacterial membrane to find their intracellular target. Peptide specificity was confirmed by overproduction of the putative target (DnaN) which resulted in resistance. The minimum inhibitory concentration was ∼50 μg/ml for S. aureus cells. These compounds may serve as lead candidates for future development into novel classes of antibiotics as well as provide information on the function of the S. aureus replication process.
doi:10.1371/journal.pone.0072273
PMCID: PMC3762901  PMID: 24023733
24.  Correlation between centromere protein-F autoantibodies and cancer analyzed by enzyme-linked immunosorbent assay 
Molecular Cancer  2013;12:95.
Background
Centromere protein-F (CENP-F) is a large nuclear protein of 367 kDa, which is involved in multiple mitosis-related events such as proper assembly of the kinetochores, stabilization of heterochromatin, chromosome alignment and mitotic checkpoint signaling. Several studies have shown a correlation between CENP-F and cancer, e.g. the expression of CENP-F has been described to be upregulated in cancer cells. Furthermore, several studies have described a significant correlation between the expression of autoantibodies to CENP-F and cancer.
Methods
Autoantibodies to CENP-F were detected in a small number of samples during routine indirect immunofluorescence (IIF) analysis for anti-nuclear antibodies (ANA) using HEp-2 cells as substrate. Using overlapping synthetic peptides covering a predicted structural maintenance of chromosomes (SMC) domain, we developed an enzyme-linked immunosorbent assay (ELISA) for detection of CENP-F antibodies.
Results
Analyzing the reactivity of the sera positive in IIF for CENP-F antibodies to overlapping CENP-F peptides, we showed that autoantibodies to several peptides correlate with the presence of antibodies to CENP-F and a diagnosis of cancer, as increased CENP-F antibody expression specific for malignant cancer patients to five peptides was found (A9, A12, A14, A16, A27). These antibodies to CENP-F in clinical samples submitted for ANA analysis were found to have a positive predictive value for cancer of 50%. Furthermore, the expression of cancer-correlated CENP-F antibodies seemed to increase as a function of time from diagnosis.
Conclusion
These results conform to previous findings that approximately 50% of those patients clinically tested for ANA analyses who express CENP-F antibodies are diagnosed with cancer, confirming that these antibodies may function as circulating tumor markers. Thus, a peptide-based CENP-F ELISA focused on the SMC domain may aid in identifying individuals with a potential cancer.
doi:10.1186/1476-4598-12-95
PMCID: PMC3844405  PMID: 23978088
Centromere protein-F; Autoantibodies; Immunofluorescence; ELISA; Cancer
25.  Cerebrovascular risk factors and brain microstructural abnormalities on diffusion tensor images in HIV-infected individuals 
Journal of neurovirology  2012;18(4):303-312.
HIV-associated neurocognitive disorder remains prevalent in HIV-infected individuals despite effective antiretroviral therapy. As these individuals age, comorbid cerebrovascular disease will likely impact cognitive function. Effective tools to study this impact are needed. This study used diffusion tensor imaging (DTI) to characterize brain microstructural changes in HIV-infected individuals with and without cerebrovascular risk factors. Diffusion-weighted MRIs were obtained in 22 HIV-infected subjects aged 50 years or older (mean age = 58 years, standard deviation = 6 years; 19 males, three females). Tensors were calculated to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps. Statistical comparisons accounting for multiple comparisons were made between groups with and without cerebrovascular risk factors. Abnormal glucose metabolism (i.e., impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus) was associated with significantly higher MD (false discovery rate (FDR) critical p value = 0.008) and lower FA FDR critical p value = 0.002) in the caudate and lower FA in the hippocampus (FDR critical p value = 0.004). Pearson correlations were performed between DTI measures in the caudate and hippocampus and age- and education-adjusted composite scores of global cognitive function, memory, and psychomotor speed. There were no detectable correlations between the neuroimaging measures and measures of cognition. In summary, we demonstrate that brain microstructural abnormalities are associated with abnormal glucose metabolism in the caudate and hippocampus of HIV-infected individuals. Deep gray matter structures and the hippocampus may be vulnerable in subjects with comorbid abnormal glucose metabolism, but our results should be confirmed in further studies.
doi:10.1007/s13365-012-0106-1
PMCID: PMC3420956  PMID: 22585287
HIV; Cerebrovascular disease; Diffusion tensor imaging

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