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4 Episodic Memory Deficits and Fronto-Limbic Correlates in Older Adults Living with HIV: Comparison to Parkinson’s Disease and Normal Aging
- Rosemary Fama, Eva M. Müller-Oehring, Taylor F. Levine, Edith V. Sulivan, Priya Asok, Stephanie A. Sassoon, Helen M. Bronte-Stewart, Kathleen L. Poston, Kilian M. Pohl, Adolf Pfefferbaum, Tilman Schulte
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 679
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Objective:
The prevalence of mild to moderate cognitive impairment, including episodic memory deficits, in people living with HIV (PLWH) remains high despite the life-extending success of antiretroviral pharmacotherapy. With PLWH now reaching near-normal life expectancy, questions concerning a potential synergy between age- and HIV disease-related effects, including degradation in fronto-limbic circuits, neural systems also compromised in Parkinson’s disease (PD), have emerged.
Participants and Methods:This cross-sectional study examined the similarities and differences in component processes of verbal episodic memory and their neural correlates in 42 PLWH, 41 individuals with PD, and 37 controls (CTRL) (all participants aged 45-79 years). Learning over five trials, short-delay (SD) and long-delay, (LD), free-recall (FR) and cued-recall (CR) indices were assessed using the California Verbal Learning Test-2. Retention scores for FR and CR were derived adjusting for Trial 5 performance. All memory scores were age- and education-corrected based on the control group and reported as Z-scores. Regional brain volumes were calculated using 3T MRI data and the SRI24 atlas to delineate frontal (precentral, superior, orbital, middle, inferior, supplemental motor, and medial) and limbic (hippocampus, thalamus) regions. Brain volumes were age- and head-sized corrected based on 238 controls (19-86 years old).
Results:Compared with the CTRL group, the HIV and PD groups were impaired on learning across trials and on SD and LD free- and cued-recall, with no group difference between the HIV and PD groups on any score. All three groups benefited similarly from cues compared with free-recall. The HIV and PD groups did not differ from CTRL on retention scores. Regarding brain volumes, the HIV group had smaller middle frontal volumes than the PD or CTRL groups and smaller thalamic volumes than the PD group. Correlational analyses (Bonferroni correction for 8 comparisons, p<.01) indicated that fewer total number of words recalled on Trial 5, learning over Trials 1-5, total words recalled on SD-CR, LD-FR, and LD-CR were associated with smaller orbitofrontal volume in the HIV but not the PD group; the correlations between orbitofrontal volume and memory scores were significantly different between the HIV and PD groups. In PD, but not HIV, lower retention scores on SD-FR and LD-CR correlated to smaller hippocampal volume.
Conclusions:Impairment in learning and cued recall performance indicate that both encoding and retrieval processes are affected in PLWH and PD. Neural correlates of verbal memory differed between groups, with orbitofrontal volume associated with learning and recall in PLWH, whereas hippocampal volume was associated with retention scores in PD. Together, these results suggest that different nodes within the fronto-limbic mnemonic circuitry underlie the mutual verbal episodic memory deficits observed in older PLWH and PD. Support: AA023165, AA005965, AA107347, AA010723, NS07097, MH113406, and the Michael J. Fox Foundation for Parkinson’s Research
Evaluating Metagenomic Analysis for Pathogen Transmission in Healthcare Settings
- Curt Hewitt, Katharina Weber, Danielle LeSassier, Anthony Kappell, Kathleen Schulte, Nicole Westfall, Nicolette Albright, Gene Godbold, Veena Palsikar, Carlos Acevedo, Krista Ternus
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 41 / Issue S1 / October 2020
- Published online by Cambridge University Press:
- 02 November 2020, p. s224
- Print publication:
- October 2020
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Background: The prevalence of healthcare-acquired infections (HAIs) and rising levels of antimicrobial resistance place a significant burden on modern healthcare systems. Cultures are typically used to track HAIs; however, culture methods provide limited information and are not applicable to all pathogens. Next-generation sequencing (NGS) can detect and characterize pathogens present within a sample, but few research studies have explored how NGS could be used to detect pathogen transmission events under HAI-relevant scenarios. The objective of this CDC-funded project was to evaluate and correlate sequencing approaches for pathogen transmission with standard culture-based analysis. Methods: We modeled pathogen transfer via hand contact using synthetic skin. These skin coupons were seeded with a community of commensal organisms to mimic the human skin microbiome. Pathogens were added at physiologically relevant high or low levels prior to skin-to-skin contact. The ESKAPE pathogens: E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter spp plus C. difficile were employed because they are the most common antibiotic resistant HAIs. Pathogen transfer between skin coupons was measured following direct skin contact and fomite surface transmission. The effects of handwashing or fomite decontamination were also evaluated. Transferred pathogens were enumerated via culture to establish a robust data set against which DNA and RNA sequence analyses of the same samples could be compared. These data also provide a quantitative assessment of individual ESKAPE+C pathogen transfer rates in skin contact scenarios. Results: Metagenomic and metatranscriptomic analysis using custom analysis pipelines and reference databases successfully identified the commensal and pathogenic organisms present in each sample at the species level. This analysis also identified antibiotic resistance genes and plasmids. Metatranscriptomic analysis permitted not only gene identification but also confirmation of gene expression, a critical factor in the evaluation of antibiotic resistance. DNA analysis does not require cell viability, a key differentiator between sequencing and culturing reflected in simulated handwashing data. Sensitivity remains a key limitation of metagenomic analysis, as shown by the poor species identification and gene content characterization of pathogens present at low abundance within the simulated microbial community. Species level identification typically failed as ratios fell below 1:1,000 pathogen CFU:total community CFU. Conclusions: These findings demonstrate the strengths and weaknesses of NGS for molecular epidemiology. The data sets produced for this study are publicly available so they can be employed for future metagenomic benchmarking studies.
Funding: None
Disclosures: None
Notes on contributors
- Edited by Elvira Pulitano, California Polytechnic State University
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- Book:
- Indigenous Rights in the Age of the UN Declaration
- Published online:
- 05 June 2012
- Print publication:
- 24 May 2012, pp ix-xiii
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