Keeping in step with the young: Chronometric and kinematic data show intact procedural locomotor sequence learning in older adults.

Sequence learning in serial reaction time tasks (SRTT) is an established, lab-based experimental paradigm to study acquisition and transfer of skill based on the detection of predictable stimulus and motor response sequences. Sequence learning has been mainly studied in key presses using visual target stimuli and is demonstrated by better performance in predictable sequences than in random sequences. In this study, we investigated sequence learning in the context of more complex locomotor responses. To this end, we developed a novel goal-directed stepping SRTT with auditory target stimuli in order to subsequently assess the effect of aging on sequence learning in this task, expecting that age-related performance reductions in postural control might disturb the acquisition of the sequence. We used pressure-sensitive floor mats to characterise performance across ten blocks of trials. In Experiment 1, 22 young adults demonstrated successful acquisition of the sequence in terms of the time to step on the target mat and percent error and thus validated our new paradigm. In Experiment 2, in order to contrast performance improvements in the stepping SRTT between 27 young and 22 old adults, motion capture of the feet was combined with the floor mat system to delineate individual movement phases during stepping onto a target mat. The latencies of several postural events as well as other movement parameters of a step were assessed. We observed significant learning effects in the latency of step initiation, the time to step on the target mat, and motion parameters such as stepping amplitude and peak stepping velocity, as well as in percent error. The data showed general age-related slowing but no significant performance differences in procedural locomotor sequence learning between young and old adults. The older adults also had comparable conscious representations of the sequence of stimuli as the young adults. We conclude that sequence learning occurred in this locomotor learning task that is much more complex than typical finger-tapping sequence learning tasks, and that healthy older adults showed similar learning effects compared to young adults, suggesting intact locomotor sequence learning capabilities despite general slowing and normal age-related decline in sensorimotor function.

Association between cervical dysplasia and human papillomavirus in HIV seropositive women from Johannesburg South Africa.

OBJECTIVE: To examine the association between CD4 counts, HPV infection and the risk of cervical neoplasia among HIV-seropositive women. METHODS: A cross-sectional observational study was conducted among 1,010 HIV-seropositive women using cytology-based Pap smears. HPV DNA testing using Linear Array genotyping assay (Roche) was carried out in a subset of 191 patients. Multivariable-adjusted prevalence ratios (mPR) and 95% confidence intervals (CIs) were estimated with log-binomial regression. RESULTS: Among 1,010 HIV-seropositive women, the prevalence of AGC/ASCUS, LSIL and HSIL or greater was 8.3, 23.5 and 18.0%, respectively. The risk of cervical lesions was higher with CD4 < 200 cells/mm(3) vs. CD4 levels > 500/mm(3). HPV types 16 (41.7%) and HPV 56 (22.2%) were the most common types in HSIL cases. Women with CD4 levels < 200/mm(3) had a higher prevalence of HPV types 16 (p < 0.01) and 66 (p = 0.04). No statistical relationship between cervical lesions and HAART use was found. CONCLUSION: The burden of HPV infection and HSIL was high and correlated with HIV-induced immunosuppression. HPV 16 was the most common type in HSIL and increased in prevalence with greater immune suppression. Prophylactic HPV 16 vaccination could prevent approximately 40% of HSIL cases. Strengthening screening programs is imperative in this population.

Atypical squamous cells, cannot exclude high grade squamous intraepithelial (ASC-H) in HIV-positive women.

OBJECTIVE: South Africa has very high rates of both HIV infection and cervical pathology. The management of ASC-H is colposcopy and directed biopsy, but with so many women diagnosed with HSIL and a dearth of colposcopy centres in South Africa, women with cytologic diagnosis of ASC-H may not be prioritized for colposcopy. The aim of this study was to determine if HIV-positive women with a cytologic diagnosis of ASC-H should undergo immediate colposcopy or whether colposcopy can be delayed, within the context of an underfunded health care setting with so many competing health needs. MATERIALS AND METHODS: A computer database search was performed from the archives of an NGO-administered clinic that offers comprehensive HIV care. All women with a cytologic diagnosis of ASC-H on cervical smears from September 2005 until August 2009 were identified. Histologic follow up was sought in all patients. RESULTS: A total of 2111 cervical smears were performed and 41 diagnosed as ASC-H (1.94%). No histologic follow up data was available in 15 cases. Follow up histologic results were as follows: three negative (11.5%), five koilocytosis and/ or CIN1 (19.2%), ten CIN2 (38.5%) and eight CIN3 (30.8%). There were no cases of invasive carcinoma on follow up. CONCLUSION: The current appropriate management of HIV-positive women in low-resource settings with a diagnosis of ASC-H on cervical smear is colposcopy, despite the costs involved. In the future and if cost-effective in developing nations, use of novel markers may help select which HIV-positive women can be managed conservatively and which ones referred for more active treatment. More research in this regard is warranted.

Charles Bonnet Syndrome: successful treatment of visual hallucinations due to vision loss with selective serotonin reuptake inhibitors.

Visual hallucinations are a common and often distressing consequence of vision loss, particularly in age-related macular degeneration. Charles Bonnet Syndrome (CBS) is defined by the triad of complex visual hallucinations, ocular pathology causing visual deterioration and preserved cognitive status. So far, although this condition is frequent, no established treatment for CBS has been stated. We report here the case of a 78-year-old woman, who came in our hospital because of a 4-week long mild depressive symptomatology. For 1 year she experienced daily sudden, unexpected, vivid and elaborate hallucinations. Insight was completely present, so the patient stated that the hallucinations were unreal and that the faces, geometrical figures and animals she saw every day were possibly due to her vision loss. The Mini Mental State Examination, digit span and verbal fluency were administered and no cognitive impairment was reported. The visual acuity was hand motion. After 4 days of treatment with venlafaxine the hallucinations completely disappeared. This is the first case to show that selective serotonin (and noradrenalin) reuptake inhibitors may be an effective and well-tolerated treatment for visual hallucinations associated with vision loss, and it adds to evidence implicating serotonergic pathways in the pathogenesis of visual hallucinations.

Injectable and oral contraception and the incidence and progression of cervical disease in HIV-infected women in South Africa.

BACKGROUND: Few data exist regarding the effect of hormonal contraception (HC) on incidence and progression of cervical disease (e.g., cervical dysplasia, squamous intraepithelial lesions, cervical intraepithelial neoplasia) in HIV-infected African women. STUDY DESIGN: We conducted an observational study of HIV-seropositive women in Johannesburg, South Africa. The effect of individual HC types on the incidence and progression of cervical disease was determined using Poisson regression to obtain adjusted incidence rate ratios. RESULTS: We evaluated 594 HIV-infected women, with median follow-up time of 445 days; 75 of these women were receiving some form of HC (largely DMPA, NET-EN, or COCs) at baseline. Risks of incidence and progression of cervical disease were similar comparing women not receiving HCs to women receiving DMPA, NET-EN, or COCs both individually by HC-type and considering all HC together. CONCLUSIONS: There was no statistically significant effect of particular HC methods or of HC use in general on rates of incidence or progression of cervical disease in this study. These results should reassure us that use of HC is unlikely to substantially increase risks of cervical disease among HIV-positive women.

Highly active antiretroviral therapy and cervical dysplasia in HIV-positive women in South Africa.

BACKGROUND: The risk of squamous intra-epithelial lesions (SIL) is higher in HIV-positive women. As these women begin to live longer due to highly active antiretroviral therapy (HAART), their risk of cervical cancer may increase. Few data exist regarding the effect of HAART on the incidence and progression of SIL in HIV-positive African women. The aim of this study was to evaluate the effect of HAART on the incidence and progression of SIL in HIV-positive women in South Africa. METHODS: A prospective observational study of HIV-seropositive women was conducted over 5 years in an HIV treatment clinic in Johannesburg, South Africa. The participants consisted of 601 women on and off HAART who had repeat Pap smears greater than 6 months apart. The effect of HAART use on incidence and progression rates of SIL was determined using multivariate Poisson regression to obtain incidence rate ratios (IRRs), adjusted for age, CD4 count and other potential confounders. RESULTS: Median follow-up time was 445 days (inter-quartile range 383, 671). The crude rate of incidence of any SIL was 15.9 episodes (95% confidence limit (CL) 12.7, 19.9) per 100 person-years; the crude rate of all progression of cervical dysplasia among women was 13.5 episodes (95% CL 11.3, 16.1) per 100 person-years. HAART use was associated with a robust reduction in the rate of incidence and progression of cervical lesions, adjusted IRR=0.55 (95% CL 0.37, 0.80). Sensitivity analyses confirmed this main association held for incidence and progression when they were considered separately, and that the result was not dependent on the length of HAART exposure. CONCLUSION: HAART use was associated with a reduction in the rate of both incidence and progression of cervical lesions among HIV-positive women.

Randomized trial of time-limited interruptions of protease inhibitor-based antiretroviral therapy (ART) vs. continuous therapy for HIV-1 infection.

BACKGROUND: The clinical outcomes of short interruptions of PI-based ART regimens remains undefined. METHODS: A 2-arm non-inferiority trial was conducted on 53 HIV-1 infected South African participants with viral load <50 copies/ml and CD4 T cell count >450 cells/µl on stavudine (or zidovudine), lamivudine and lopinavir/ritonavir. Subjects were randomized to a) sequential 2, 4 and 8-week ART interruptions or b) continuous ART (cART). Primary analysis was based on the proportion of CD4 count >350 cells(c)/ml over 72 weeks. Adherence, HIV-1 drug resistance, and CD4 count rise over time were analyzed as secondary endpoints. RESULTS: The proportions of CD4 counts >350 cells/µl were 82.12% for the intermittent arm and 93.73 for the cART arm; the difference of 11.95% was above the defined 10% threshold for non-inferiority (upper limit of 97.5% CI, 24.1%; 2-sided CI: -0.16, 23.1). No clinically significant differences in opportunistic infections, adverse events, adherence or viral resistance were noted; after randomization, long-term CD4 rise was observed only in the cART arm. CONCLUSION: We are unable to conclude that short PI-based ART interruptions are non-inferior to cART in retention of immune reconstitution; however, short interruptions did not lead to a greater rate of resistance mutations or adverse events than cART suggesting that this regimen may be more forgiving than NNRTIs if interruptions in therapy occur. TRIAL REGISTRATION: ClinicalTrials.gov NCT00100646.

HIV-HBV coinfection among South African patients receiving antiretroviral therapy.

There are approximately 33 million individuals with HIV infection worldwide. The majority of infections are in southern Africa where hepatitis B is also known to be endemic. As access to life-saving antiretroviral therapy (ART) increases, the possibility for hepatitis B treatment resistance increases because most ART regimens contain lamivudine. Patients coinfected with HBV are therefore receiving monotherapy for HBV infection, leading to possible HBV-resistant mutants and the concurrent public health effect thereof. Additional information is needed on the prevalence of HIV-HBV coinfection and treatment response to ART. We present a summary of the information available from South Africa to date.

Association between HIV replication and serum leptin levels: an observational study of a cohort of HIV-1-infected South African women.

BACKGROUND: Advanced HIV infection can result in lipoatrophy and wasting, even in the absence of ongoing opportunistic infections, suggesting that HIV may directly affect adipose tissue amount and distribution. METHODS: We assessed the relationship of fat (measured using anthropometry, DEXA, MRI scans) or markers related to glucose and lipid metabolism with viral load in a cross-sectional sample of 83 antiretroviral-naïve HIV-1-infected South African women. A multivariable linear model was fitted to log10VL to assess the combined effect of these variables. RESULTS: In addition to higher T cell activation, women with viral load greater than the population median had lower waist circumference, body mass index and subcutaneous abdominal fat, as well as lower serum leptin. We demonstrate that leptin serum levels are inversely associated with viral replication, independent of the amount of adipose tissue. This association is maintained after adjusting for multiple variables associated with disease progression (i.e., cellular activation and innate immunity effector levels). CONCLUSIONS: Our results demonstrate that serum leptin levels are inversely associated with viral replication, independent of disease progression: we postulate that leptin may affect viral replication.

The prevalence of hepatitis B co-infection in a South African urban government HIV clinic.

OBJECTIVE: There are an estimated 350 million hepatitis B carriers worldwide. In South Africa the prevalence of mono-infection with hepatitis B has been estimated to range from 1% in urban areas to approximately 10% in rural areas. The exact prevalence of hepatitis B in the HIV-infected population has not been well established. Hepatitis B screening is not standard practice in government HIV clinics. Co-infection with hepatitis B and HIV can influence antiretroviral treatment and prognosis of both diseases. The purpose of this study was to evaluate the prevalence of hepatitis B/HIV coinfection. DESIGN: This is believed to be the first prospective observational report on the prevalence of hepatitis B/HIV co-infection in South Africa. Patients on whom hepatitis B serological tests could not have been done previously were recruited from an HIV clinic in a regional hospital in Johannesburg. Standard hepatitis B serological tests were performed. RESULTS: Five hundred and two participants were screened. The cohort's average age was 37 +/- 9 years and the average CD4 count was 128 cells/pi. Twenty-four (4.80%) were hepatitis B surface antigen positive. Nearly half (47%) of the participants showed some evidence of hepatitis B exposure. The risk of hepatitis B co-infection was not significantly different when analysed in terms of sex, race, CD4 count or age. Liver function tests were not a good predictor of hepatitis B infection. CONCLUSION: The rate of hepatitis B infection, as defined by hepatitis B surface antigen positivity in HIV-infected individuals in urban South Africa was 5 times the rate in people who were not HIV-infected. A 5% rate of hepatitis B/HIV co-infection is a reason to increase the accessibility of tenofovir/emtricitabine (Truvada) for first-line treatment for this population.