The purpose of the two experiments was to investigate the potential effects of different types of visualizations and self-explanation prompts on learning human cardiovascular system in a multimedia ...environment. In Experiments 1 and 2, 70 and 44 college students were randomly assigned to one of the four conditions in a 2 × 2 factorial design with visualization type (animated vs. static) and prompting self-explanations (prompts vs. none) as the between subjects factors. The results of Experiment 1 revealed a positive effect of prompts on learning outcomes. Experiment 2, in which the no-prompts conditions were re-designed, partially replicated the results of Experiment 1. In addition, it revealed a significant interaction between the two factors on learning time, learning outcomes, and goal-driven self-explanations. The results of both experiments suggest that instructional designers should pay attention to learners' cognitive aspects, and utilize the combination of animated visualizations and self-explanation prompts when designing multimedia environments.
We examined the joint effects of depressive symptoms (Beck Depression Inventory-II (BDI-II)) and systemic inflammation (plasma C-reactive protein (CRP)) on longitudinal profiles of neurocognition in ...a cohort of 143 people with HIV (PWH) on antiretroviral therapy. Global neurocognition, processing speed, motor skills, and attention/working memory all worsened as CRP increased but only among PWH who, on average, exhibited moderate to severe depressive symptoms (BDI-II > 22). Findings suggest that some PWH with chronically elevated depressive symptoms may have an inflammatory subtype of depression and a particular vulnerability to neurocognitive changes that may respond to drugs targeting inflammation or its neural sequelae.
Neurocognitive Impact of Substance Use in HIV Infection Byrd, Desiree A; Fellows, Robert P; Morgello, Susan ...
Journal of acquired immune deficiency syndromes (1999),
2011-October-1, Letnik:
58, Številka:
2
Journal Article
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BACKGROUND:To determine how serious a confound substance use (SU) might be in studies on HIV-associated neurocognitive disorder (HAND), we examined the relationship of SU history to neurocognitive ...impairment (NCI) in participants enrolled in the Central Nervous System HIV Antiretroviral Therapy Effects Research study.
METHODS:After excluding cases with behavioral evidence of acute intoxication and histories of factors that independently could account for NCI (eg, stroke), baseline demographic, medical, SU, and neurocognitive data were analyzed from 399 participants. Potential SU risk for NCI was determined by the following criterialifetime SU Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis, self-report of marked lifetime SU, or positive urine toxicology. Participants were divided into 3 groups as followsno SU (n = 134), nonsyndromic SU (n = 131), syndromic SU (n = 134) and matched on literacy level, nadir CD4, and depressive symptoms.
RESULTS:Although approximately 50% of the participants were diagnosed with HAND, a multivariate analysis of covariance of neurocogntive summary scores, covarying for urine toxicology, revealed no significant effect of SU status. Correlational analyses indicated weak associations between lifetime heroin dosage and poor recall and working memory and between cannabis and cocaine use and better verbal fluency.
CONCLUSIONS:These data indicate that HIV neurocognitive effects are seen at about the same frequency in those with and without historic substance abuse in cases that are equated on other factors that might contribute to NCI. Therefore, studies on neuroAIDS and its treatment need not exclude such cases. However, the effects of acute SU and current SU disorders on HAND require further study.
A cochlear implant can restore hearing function by electrically exciting spiral ganglion neurons (SGNs) in the deaf cochlea. However, following deafness SGNs undergo progressive degeneration ...ultimately leading to their death. One significant cause of SGN degeneration is the loss of neurotrophic support that is normally provided by cells within the organ of Corti (OC). The administration of exogenous neurotrophins (NTs) can protect SGNs from degeneration but the effects are short-lived once the source of NTs has been exhausted. NT gene therapy, whereby cells within the cochlea are transfected with genes enabling them to produce NTs, is one strategy for providing a cellular source of NTs that may provide long-term support for SGNs. As the SGNs normally innervate sensory cells within the OC, targeting residual OC cells for gene therapy in the deaf cochlea may provide a source of NTs for SGN protection and targeted regrowth of their peripheral fibers. However, the continual degeneration of the OC over extended periods of deafness may deplete the cellular targets for NT gene therapy and hence limit the effectiveness of this method in preventing SGN loss. This study examined the effects of deafness duration on the efficacy of NT gene therapy in preventing SGN loss in guinea pigs that were systemically deafened with aminoglycosides. Adenoviral vectors containing green fluorescent protein (GFP) with or without genes for Brain Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT3) were injected into the scala media (SM) compartment of cochleae that had been deafened for one, four or eight weeks prior to the viral injection. The results showed that viral transfection of cells within the SM was still possible even after severe degeneration of the OC. Supporting cells (pillar and Deiters’ cells), cells within the stria vascularis, the spiral ligament, endosteal cells lining the scala compartments and interdental cells in the spiral limbus were transfected. However, the level of transfection was remarkably lower following longer durations of deafness. There was a significant increase in SGN survival in the entire basal turn for cochleae that received NT gene therapy compared to the untreated contralateral control cochleae for the one week deaf group. In the four week deaf group significant SGN survival was observed in the lower basal turn only. There was no increase in SGN survival for the eight week deaf group in any cochlear region. These findings indicated that the efficacy of NT gene therapy diminished with increasing durations of deafness leading to reduced benefits in terms of SGN protection. Clinically, there remains a window of opportunity in which NT gene therapy can provide ongoing trophic support for SGNs.
► Neurotrophin gene therapy was observed in the degenerating organ of Corti. ► Gene therapy was primarily localised to the basal cochlear regions. ► Reduced transfection was observed with longer pre-treatment durations of deafness. ► Significant SGN survival was seen following short pre-treatment deafness durations. ► No significant SGN survival was seen after longer pre-treatment deafness durations.
Abstract Background Prior research has demonstrated neuropsychological (NP) impairment in persons with histories of injection drug use (IDU), hepatitis C virus (HCV) infection, and methadone ...maintenance treatment (MMT), individually, but little is known about the NP effects of these three risk factors in combination. This issue is particularly important in China, which is addressing its highly HCV-comorbid IDU epidemic with widespread government sponsored MMT, especially in light of recent evidence suggesting that methadone may be neuroprotective in some circumstances. Methods We administered a comprehensive NP test battery to 195 Chinese heroin IDU individuals taking MMT (IDU+ group), the majority of whom were also HCV+ (87%; n = 169), and compared their NP performance to that of 198 demographically comparable, non-IDU Chinese controls (IDU− group). All participants in both groups tested negative for HIV infection, which is also a common comorbidity in the Chinese IDU population. Results The IDU+ group did not have an increased rate of global NP impairment, or perform significantly worse on any individual NP test measure. Within the IDU+ group, liver disease characteristics and reported details of heroin use were not significantly associated with NP performance. Conclusion Failure to detect NP impairment in IDU+ subjects with or without HCV infection was surprising, particularly considering the previously demonstrated sensitivity of our NP battery to neurocognitive disorders associated with HIV infection in China. One possible explanation, which should be explored in future research, is the potential neuroprotective effect of methadone in the context of HCV infection and/or heroin withdrawal.
Unbound tissue-to-plasma partition coefficients (Kpuu) were determined for 56 structurally diverse compounds in rats following intravenous infusion. Five tissues were included in the study: white ...adipose, brain, heart, liver, and skeletal muscle. The rank ordering of the median tissue Kpuu values was: liver (4.5) > heart (1.8) > adipose (1.2) > skeletal muscle (0.6) > brain (0.05), with liver being most enriched and brain most impaired. The median Kpuu values of acids and zwitterions were lower than those of bases and neutrals in all tissues but liver. Selective tissue distribution was observed, dependent upon chemotype, which demonstrated the feasibility of targeting or restricting drug exposure in certain tissues through rational design. Physicochemical attributes for Kpuu were identified using recursive partitioning, which further classified compounds with enriched or impaired tissue distribution. The attributes identified provided valuable insight on design principles for asymmetric tissue distribution to improve efficacy or reduce toxicity.
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•Compounds demonstrate unique tissue distributions depending on structural characteristics.•It is feasible to achieve asymmetric tissue distribution through rational medicinal chemistry design.•Enriched tissue exposure has been observed for compounds in all ionization classes.•Transporters not only transport ionizable compounds, but also neutrals.•Liver is the most enriched tissue; brain, most impaired; and heart, most unimpaired.
Chronic use of methamphetamine (MA) is associated with neuropsychological dysfunction and affective distress. Some normalization of function has been reported after abstinence, but little in the way ...of data is available on the possible added benefits of long-term sobriety. To address this, we performed detailed neuropsychological and affective evaluations in 83 MA-dependent individuals at a baseline visit and following an average one-year interval period. Among the 83 MA-dependent participants, 25 remained abstinent, and 58 used MA at least once during the interval period. A total of 38 non-MA-addicted, demographically matched healthy comparison (i.e., HC) participants were also examined. At baseline, both MA-dependent participants who were able to maintain abstinence and those who were not performed significantly worse than the healthy comparison subjects on global neuropsychological functioning and were significantly more distressed. At the one-year follow-up, both the long-term abstainers and healthy comparison groups showed comparable global neuropsychological performance and affective distress levels, whereas the MA-dependent group who continued to use MA were worse than the comparison participants in terms of global neuropsychological functioning and affective distress. An interaction was observed between neuropsychological impairment at baseline, MA abstinence, and cognitive improvement, with abstinent MA-dependent participants who were neuropsychologically impaired at baseline demonstrating significantly and disproportionately greater improvement in processing speed and slightly greater improvement in motor abilities than the other participants. These results suggest partial recovery of neuropsychological functioning and improvement in affective distress upon sustained abstinence from MA that may extend beyond a year or more.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background. Neurocognitive disorders remain common among human immunodeficiency virus (HIV)–positive adults, perhaps owing to persistent HIV-1 RNA in cerebrospinal fluid (CSF) during antiretroviral ...therapy (ART). Methods. Using a single-copy assay, we measured HIV-1 RNA levels in CSF and plasma specimens from 220 HIV-positive adults who were taking suppressive ART. Fifty-five participants were tested twice. Results. HIV-1 RNA was detected in 42.3% of CSF and 65.2% of plasma samples. Correlates of higher CSF HIV-1 RNA levels included higher nadir and current CD4⁺ T-cell counts, a plasma HIV-1 RNA level of ≥ 1 copy/mL, and a lower central nervous system penetration-effectiveness score (model P < .001). Worse neurocognitive performance was associated with discordance in HIV-1 RNA detection between plasma and CSF, lower overall CSF HIV-1 RNA level, and longer ART duration, among others (model P < .001). In the longitudinal subgroup, CSF HIV-1 RNA persisted in most participants (69%) over 7 months. Conclusions. Low-level HIV-1 RNA in CSF is common during suppressive ART and is associated with low-level HIV-1 RNA in blood, better immune status, and lower ART drug distribution into CSF. The association between HIV-1 RNA discordance and HIV-associated neurocognitive disorder (HAND) may reflect compartmentalization. The relationship between HAND, lower HIV-1 RNA levels in CSF, and lower CD4⁺ T-cell counts may reflect disturbances in the immune response to HIV-1 in the CNS.
This review describes parts of our research program on example-based learning that relates to recent efforts to incorporate interactive elements into learning environments designed to support ...learning from worked-out examples. Since most learners spontaneously study or process examples in a very passive or superficial manner, this review focuses on how a variety of specific interactive elements in example-based leaning environments are capable of encouraging learners to actively process the examples. The review begins with an overview of the literature on worked examples and the associated self-explanation, which is important given that the quality of self-explanation is a major factor in determining whether learners benefit from studying examples. The review notes that example-based learning environments tend to be effective but often promote passive processing. It then highlights the strengths and limitations of three types interactivity introduced to example-based learning environments. The review concludes with a discussion of the role that these interactive elements play in these learning environments.
OBJECTIVE:The influence of confounding neurocognitive comorbidities in people living with HIV (PLWH) on neuroimaging has not been systematically evaluated. We determined associations between ...comorbidity burden and brain integrity and examined the moderating effect of age on these relationships.
DESIGN:Observational, cross-sectional substudy of the CNS HIV Antiretroviral Therapy Effects Research cohort.
METHODS:A total of 288 PLWH (mean age = 44.2) underwent structural MRI and magnetic resonance spectroscopy as well as neurocognitive and neuromedical assessments. Consistent with Frascati criteria for HIV-associated neurocognitive disorders (HAND), neuromedical and neuropsychiatric comorbidity burden was classified as incidental (mild), contributing (moderate), or confounding (severe-exclusionary) to a diagnosis of HAND. Multiple regression modeling predicted neuroimaging outcomes as a function of comorbidity classification, age, and their interaction.
RESULTS:Comorbidity classifications were 176 incidental, 77 contributing, and 35 confounded; groups did not differ in HIV disease characteristics. Relative to incidental and contributing participants, confounded participants had less cortical gray matter and more abnormal white matter and ventricular cerebrospinal fluid, alongside more neuroinflammation (choline, myo-inositol) and less neuronal integrity (N-acetylaspartate). Older age exacerbated the impact of comorbidity burdento a greater extent in the confounded group, older age was associated with more abnormal white matter (P = 0.017), less total white matter (P = 0.015), and less subcortical gray matter (P = 0.014).
CONCLUSION:Neuroimaging in PLWH reveals signatures associated with confounding neurocognitive conditions, emphasizing the importance of evaluating these among individuals with suspected HAND. Older age amplifies subcortical and white matter tissue injury, especially in PLWH with severe comorbidity burden, warranting increased attention to this population as it ages.
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