The perception of song is vital to the reproductive success of both male and female songbirds. Several neural structures underlying this perception have been identified by examining expression of immediate early genes (IEGs) following the presentation of conspecific or heterospecific song. In the few avian species investigated, areas outside of the circuit for song production contain neurons that are active following song presentation, specifically the caudal hyperstriatum ventrale (cHV) and caudomedial neostriatum (NCM). While studied in detail in the male zebra finch, IEG responses in these neural substrates involved in song perception have not been quantified in females. Therefore, adult female zebra finches were presented with zebra finch song, nonzebra finch song, randomly generated tones, or silence for 30 min. One hour later they were sacrificed, and their brains removed, sectioned, and immunocytochemically processed for FOS expression. Animals exposed to zebra finch song had a significantly higher density of FOS-immunoreactive cells in the NCM than those presented with other songs, tones, or silence. Neuronal activation in the cHV was equivalent in birds that heard zebra finch and non-zebra finch song, expression that was higher than that observed in the groups that heard no song. Interestingly, the hippocampus (HP) and adjacent parahippocampal area (AHP) were activated in a manner comparable to the NCM. These results suggest a general role for the cHV in song perception and a more specific role for the NCM and HP/AHP in facilitating recognition of and responsiveness to species-specific song in female zebra finches.

Vitamin D supplementation decreased markers of T-cell activation/exhaustion and monocyte activation in HIV-infected youth, with subjects given the highest dose (120,000 IU/month) showing the greatest decreases. These data suggest that high-dose vitamin D supplementation may attenuate immune activation and exhaustion, and serve as adjuvant therapy to antiretroviral therapy in HIV. ClinicalTrials.gov identifier: NCT01523496.

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Children and young adults infected with HIV are at elevated risk for cardiovascular disease (CVD). However, scarce data exist on the utility of non-invasive methods to diagnose subclinical CVD, such as pulse wave velocity (PWV), a non-invasive measure of arterial stiffness. The objectives of this study were to assess the relationship of carotid-femoral PWV with subclinical atherosclerosis measured by carotid intima-media thickness (IMT), compare measurements to healthy controls, and evaluate variables associated with PWV in HIV-infected youth. One hundred and one 8-25 year-old subjects on stable antiretroviral therapy with low-level viremia or an undetectable HIV-1 RNA were enrolled, along with 86 healthy controls similar in age, sex and race. There was no significant difference in PWV between groups (median (Q1, Q3): 5.7 (5.2, 6.3) vs 5.7 (4.9, 6.5) m/s; P = 0.81). Among the HIV-infected subjects, PWV was positively correlated with both internal carotid artery (R = 0.31, P = 0.02) and carotid bulb IMT (R = 0.29, P = 0.01). In multivariable regression, only current alcohol consumption and systolic blood pressure were independently associated with PWV in the HIV-infected group (where current alcohol consumption and higher systolic blood pressure were associated with higher PWV); whereas, age, body mass index, and current marijuana use were associated with PWV in healthy controls. In this study of PWV in HIV-infected youth, measures of arterial stiffness were not different between subjects and controls. However, in HIV-infected youth, there was a significant association between PWV and carotid IMT, as well as between PWV and current alcohol consumption. Thus, PWV may have potential as a useful, non-invasive method to assess CVD risk in HIV-infected youth, but further investigation is needed.

Background Low bone mineral density (BMD) is a significant co-morbidity in HIV. However, studies evaluating vitamin D supplementation on bone health in this population are limited. This study investigates changes in bone health parameters after 12 months of supplementation in HIV-infected youth with vitamin D insufficiency. Methods This is a randomized, active-control, double-blind trial investigating changes in bone parameters with 3 different vitamin D3 doses [18,000 (standard/control dose), 60,000 (moderate dose) and 120,000 IU/monthly (high dose)] in HIV-infected youth 8–25 years old with baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations <30 ng/mL. Bone mineral density and bone turnover markers were measured at baseline and 12 months. Results One hundred and two subjects enrolled. Over 12 months, serum 25(OH)D concentrations increased with all doses, but the high dose (i.e. 120,000 IU/monthly) maintained serum 25(OH)D concentrations in an optimal range (≥30 ng/mL or ≥20 ng/mL) throughout the study period for more subjects (85% and 93%, respectively) compared to either the moderate (54% and 88%, respectively) or standard dose (63% and 80%, respectively). All dosing groups showed some improvement in BMD; however, only the high-dose arm showed significant decreases in bone turnover markers for both procollagen type 1 amino-terminal propeptide (−3.7 ng/mL; P=0.001) and B-CrossLaps (−0.13 ng/mL; P=0.0005). Conclusions High dose vitamin D supplementation (120,000 IU/month) given over 12 months decreases bone turnover markers in HIV-infected youth with vitamin D insufficiency, which may represent an early, beneficial effect on bone health. High vitamin D doses are needed to maintain optimal serum 25(OH)D concentrations.

Background HIV-infected individuals are at increased risk of neurocognitive impairment compared to the general population. Studies suggest that, despite combination antiretroviral therapy (cART), HIV infection causes immune activation which results in neural damage; however, few data exist in HIV-infected youth. Methods HIV-infected youth 8–26 years old on cART with virologic suppression were prospectively enrolled along with healthy controls. Neurocognitive performance was assessed by age-appropriate Wechsler Intelligence Scales. Soluble and cellular markers of T-lymphocyte and monocyte activation were measured by ELISA and flow cytometry, respectively. Results 45 HIV-infected subjects and 21 controls were enrolled. Markers of T-cell and monocyte activation were higher in the HIV-infected subjects compared to controls, but proportions of inflammatory and patrolling monocytes were similar. Although there was no significant differences in neurocognitive scores between the HIV-infected and control groups, scores were low-average for 4 of 5 testing domains for the HIV-infected subjects and average for all 5 in the controls, and % of HIV-infected subjects with scores classified as “low average” or below was higher than in the controls. Variables most associated with neurocognitive performance among HIV-infected subjects included activated CD4+ T-cells (% CD4+CD38+HLA-DR), monocyte activation (soluble CD14), HIV duration, age and sex. Conclusions HIV-infected youth on cART with virologic suppression show subtle evidence of neurocognitive impairment compared to healthy controls, and increased immune activation appears to play a role. Additional studies are needed to develop strategic interventions beyond cART to potentially improve neurocognitive performance and/or minimize further impairment in this vulnerable population.

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Background Immune activation and exhaustion drive several co-morbidities and disease progression in HIV-infected adults; however, they are not well-studied in HIV-infected youth. Thus, this study sought to examine levels of immune activation and exhaustion in this population, investigate associated HIV- and non-HIV-related variables, and compare results with a matched healthy control group. Methods HIV-infected youth 8–25 years old on stable antiretroviral therapy with an HIV-1 RNA level <1000 copies/mL were enrolled, along with matched healthy controls. We measured T-cell and monocyte immune activation and exhaustion markers in cryopreserved PBMC and plasma samples. Results 136 subjects (80 HIV+: 66% male; 91% black) were enrolled. Markers of CD4+ and CD8+ T-cell activation were higher in the HIV-infected group vs. controls [mean % CD4+CD38+HLA-DR+ and CD8+CD38+HLA-DR+ = 2.2 vs. 1.5 (P=0.002) and 4.9 vs. 2.2 (P<0.0001), respectively], as were exhausted CD4+ and CD8+ T-cells [mean % CD4+CD38+HLA-DR+PD-1+ and CD8+CD38+HLA-DR+PD-1+ = 1.0 vs. 0.5 (P<0.0001) and 1.6 vs. 0.7 (P<0.0001), respectively]. There were no differences in proportions of inflammatory or patrolling monocytes between groups (P>0.05); however, soluble CD14 was higher in HIV-infected compared with controls (1.6 vs. 1.4 μg/mL; P=0.01). Current CD4 count, low-density lipoprotein cholesterol, and age were the variables most associated with CD4+ and CD8+ T-cell activation. Conclusions CD4+ and CD8+ T-cell immune activation and exhaustion are higher in HIV-infected youth compared with matched controls, while monocyte sub-populations are not altered despite a high soluble CD14 level. The clinical significance of the increased immune activation and exhaustion should be further explored.