Health literacy is associated with cognition and everyday functioning in a consecutive clinical series of people with epilepsy in a surgical setting.

OBJECTIVE: Low health literacy is common among people with epilepsy (PWE) and may play an important role in disease management and outcomes. The current study evaluated whether health literacy is related to cognition, health, and everyday functioning in PWE. METHODS: This cross-sectional, correlational study included 25 demographically comparable healthy adults retrospectively matched to a consecutive series of 89 PWE presenting for neuropsychological evaluation in a surgical setting and who completed the Newest Vital Sign and Brief Health Literacy Screener. The PWE also completed a comprehensive neuropsychological battery and measures of quality of life and everyday functioning. RESULTS: PWE had significantly lower health literacy as compared to healthy adults (ps < 0.05) at a medium-to-large effect size. In analyses covarying for education and oral word reading literacy in the PWE sample, lower health literacy was independently associated with bilateral seizure onsets, greater antiseizure medication burden, poorer performance on measures of memory and information processing speed, and difficulties with self-care (ps < 0.05). SIGNIFICANCE: Findings suggest that PWE are at risk for low health literacy, which may be partly attributable to disrupted brain-behavior relationships and contribute to poorer everyday functioning. Future studies are needed to identify effective methods to support and improve health literacy in PWE.

Human pluripotent stem cell-derived kidney organoids reveal tubular epithelial pathobiology of heterozygous HNF1B-associated dysplastic kidney malformations.

Hepatocyte nuclear factor 1B (HNF1B) encodes a transcription factor expressed in developing human kidney epithelia. Heterozygous HNF1B mutations are the commonest monogenic cause of dysplastic kidney malformations (DKMs). To understand their pathobiology, we generated heterozygous HNF1B mutant kidney organoids from CRISPR-Cas9 gene-edited human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) reprogrammed from a family with HNF1B-associated DKMs. Mutant organoids contained enlarged malformed tubules displaying deregulated cell turnover. Numerous genes implicated in Mendelian kidney tubulopathies were downregulated, and mutant tubules resisted the cyclic AMP (cAMP)-mediated dilatation seen in controls. Bulk and single-cell RNA sequencing (scRNA-seq) analyses indicated abnormal Wingless/Integrated (WNT), calcium, and glutamatergic pathways, the latter hitherto unstudied in developing kidneys. Glutamate ionotropic receptor kainate type subunit 3 (GRIK3) was upregulated in malformed mutant nephron tubules and prominent in HNF1B mutant fetal human dysplastic kidney epithelia. These results reveal morphological, molecular, and physiological roles for HNF1B in human kidney tubule differentiation and morphogenesis illuminating the developmental origin of mutant-HNF1B-causing kidney disease.

Changes in the immune landscape of TNBC after neoadjuvant chemotherapy: correlation with relapse.

Introduction: Patients with high-risk, triple negative breast cancer (TNBC) often receive neoadjuvant chemotherapy (NAC) alone or with immunotherapy. Various single-cell and spatially resolved techniques have demonstrated heterogeneity in the phenotype and distribution of macrophages and T cells in this form of breast cancer. Furthermore, recent studies in mice have implicated immune cells in perivascular (PV) areas of tumors in the regulation of metastasis and anti-tumor immunity. However, little is known of how the latter change during NAC in human TNBC or their impact on subsequent relapse, or the likely efficacy of immunotherapy given with or after NAC. Methods: We have used multiplex immunofluorescence and AI-based image analysis to compare the immune landscape in untreated and NAC-treated human TNBCs. We quantified changes in the phenotype, distribution and intercellular contacts of subsets of tumor-associated macrophages (TAMs), CD4+ and CD8+ T cells, and regulatory T cells (Tregs) in PV and non-PV various areas of the stroma and tumor cell islands. These were compared in tumors from patients who had either developed metastases or were disease-free (DF) after a three-year follow up period. Results: In tumors from patients who remained DF after NAC, there was a marked increase in stromal CD163+ TAMs, especially those expressing the negative checkpoint regulator, T-cell immunoglobulin and mucin domain 3 (TIM-3). Whereas CD4+ T cells preferentially located to PV areas in the stroma of both untreated and NAC-treated tumors, specific subsets of TAMs and Tregs only did so only after NAC. Distinct subsets of CD4+ and CD8+ T cells formed PV clusters with CD163+ TAMs and Tregs. These were retained after NAC. Discussion: Quantification of stromal TIM-3+CD163+ TAMs in tumor residues after NAC may represent a new way of identifying patients at high risk of relapse. PV clustering of immune cells is highly likely to regulate the activation and function of T cells, and thus the efficacy of T cell-based immunotherapies administered with or after NAC.

Accelerated epigenetic aging in older adults with HIV disease: associations with serostatus, HIV clinical factors, and health literacy.

The prevalence of older persons with HIV (PWH) disease has increased considerably in the last 20 years, but our understanding of biological factors of aging and their clinical correlates among PWH remains limited. Study participants were 149 persons aged 50 and older, including 107 PWH and 42 seronegatives. All participants completed a blood draw, research medical evaluation, structured psychiatric interview, neurocognitive assessment, questionnaires, and measures of health literacy. Four epigenetic clocks were generated from stored blood samples using standardized laboratory methods. In regression models adjusting for sex and smoking status, PWH had significantly higher epigenetic aging acceleration values than seronegatives on all four indicators. Within the PWH sample, higher levels of epigenetic aging acceleration were moderately associated with lower current CD4 count, AIDS diagnoses, higher scores on the Veterans Aging Cohort Study Index, and lower telomere values. Higher epigenetic aging acceleration indices were also associated with lower health literacy among PWH. PWH experience accelerated aging as measured by a series of epigenetic clocks, which may be linked to immune compromise and risk of all-cause mortality. Health literacy may be a modifiable target for mitigating the risk of accelerated aging among older PWH.

Executive functions mediate the association between alcohol use and declarative memory symptoms in daily life.

Alcohol use is associated with memory problems in young adults with HIV, but the cognitive mechanisms of that association are not known. Sixty adults (aged 19-24 years) living with HIV were administered the Alcohol, Smoking, and Substance Involvement Screening Test to assess alcohol use, Behavior Rating Inventory of Executive Function for self-reported executive functions, and the Prospective and Retrospective Memory Questionnaire (PRMQ) for dailiy memory functioning. Controlling for mood, self-reported executive functions fully mediated the relationship between alcohol use and memory (indirect effect b=.568, 95%CI [.209,.888]). Findings suggest that self-reported executive dysregulation of memory processes (e.g., Strategic encoding and retrieval) may drive the effects of alcohol use on daily memory symptoms.

Differentiation of Induced Pluripotent Stem Cells Into Chondrocytes: Methods and Applications for Disease Modeling and Drug Discovery.

Induced pluripotent stem cell (iPSC) technology allows pathomechanistic and therapeutic investigation of human heritable disorders affecting tissue types whose collection from patients is difficult or even impossible. Among them are cartilage diseases. Over the past decade, iPSC-chondrocyte disease models have been shown to exhibit several key aspects of known disease mechanisms. Concurrently, an increasing number of protocols to differentiate iPSCs into chondrocytes have been published, each with its respective (dis)advantages. In this review we provide a comprehensive overview of the different differentiation approaches, the hitherto described iPSC-chondrocyte disease models and mechanistic and/or therapeutic insights that have been derived from their investigation, and the current model limitations. Key lessons are that the most appropriate differentiation approach is dependent upon the cartilage disease under investigation and that further optimization is still required to recapitulate the in vivo cartilage. © 2022 American Society for Bone and Mineral Research (ASBMR).

Kidney organoids recapitulate human basement membrane assembly in health and disease.

Basement membranes (BMs) are complex macromolecular networks underlying all continuous layers of cells. Essential components include collagen IV and laminins, which are affected by human genetic variants leading to a range of debilitating conditions including kidney, muscle, and cerebrovascular phenotypes. We investigated the dynamics of BM assembly in human pluripotent stem cell-derived kidney organoids. We resolved their global BM composition and discovered a conserved temporal sequence in BM assembly that paralleled mammalian fetal kidneys. We identified the emergence of key BM isoforms, which were altered by a pathogenic variant in COL4A5. Integrating organoid, fetal, and adult kidney proteomes, we found dynamic regulation of BM composition through development to adulthood, and with single-cell transcriptomic analysis we mapped the cellular origins of BM components. Overall, we define the complex and dynamic nature of kidney organoid BM assembly and provide a platform for understanding its wider relevance in human development and disease.

Blood Biomarkers of Neuronal/Axonal and Glial Injury in Human Immunodeficiency Virus-Associated Neurocognitive Disorders.

INTRODUCTION: Approximately half of the people living with HIV (PLWH) experience HIV-associated neurocognitive disorders (HANDs). However, the neuropathogenesis of HAND is complex, and identifying reliable biomarkers has been challenging. METHODS: This study included 132 participants aged 50 and older from greater San Diego County. The participants were divided into three groups: PLWH with HAND (n = 29), PLWH without HAND (n = 73), and seronegatives without cognitive impairment (n = 30). Peripheral blood was collected at the clinical assessment, and plasma levels of neurofilament light chain (NfL), phosphorylated Tau 181 (pTau181), and glial fibrillary acidic protein (GFAP) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma levels of NfL (but not pTau181 and GFAP) were significantly associated with HAND at a medium effect size (p = 0.039, Cohen's d = 0.45 for HAND + vs. HAND-). Notably, higher levels of NfL were significantly associated with HAND diagnosis even after adjusting for sex. DISCUSSION: Our data suggest that neuronal degeneration (as evidenced by increased levels of NfL), but not tau pathology or glial degeneration, is related to cognitive status in PLWH. Our results corroborate the view that blood NfL is a promising biomarker of cognitive impairment in PLWH.

Apathy is not associated with a panel of biomarkers in older adults with HIV disease.

OBJECTIVE: Apathy is prevalent in HIV disease and can significantly impact personal well-being; however, little is known about its neurobiological substrates in persons with HIV (PWH) disease. METHODS: This cross-sectional, correlational study examined the association between apathy and several plasma biomarkers (tumor necrosis factor alpha, kynurenine, tryptophan, quinolinic acid, brain-derived neurotrophic factor, glial fibrillary acidic protein, neurofilament light chain, and phosphorylated tau at position threonine 181) in 109 PWH and 30 seronegative participants ages 50 and older. Apathy was measured with a composite score derived from subscales of the Frontal Systems Behavior Scale and the Profile of Mood States. RESULTS: Multiple regressions showed that PWH had significantly greater severity of apathy symptoms, independent of both data-driven and conceptually-based covariates. Pairwise correlations in the PWH sample indicated that apathy was not significantly associated with any of the measured biomarkers and all of the effect sizes were small. CONCLUSION: Findings suggest that apathy is not strongly associated with peripheral biomarkers of inflammation, neurotrophic support, or neurodegeneration in older PWH. Limitations of this study include the cross-sectional design, the use of self-report measures of apathy, and low rates of viremia. Longitudinal studies in more representative samples of PWH that include a more comprehensive panel of fluid biomarkers, informant and behavioral indicators of apathy, and relevant psychosocial factors might help to further clarify the neurobiological substrates of this complex neuropsychiatric phenomenon.

Long-term cognitive and academic outcomes among pediatric brain tumor survivors treated with proton versus photon radiotherapy.

BACKGROUND: Proton radiotherapy (PRT) may be associated with less neurocognitive risk than photon RT (XRT) for pediatric brain tumor survivors. We compared neurocognitive and academic outcomes in long-term survivors treated with XRT versus PRT. METHODS: Survivors underwent neurocognitive evaluation >1 year after craniospinal (CSI) or focal PRT or XRT. Groups were compared using separate one-way analyses of covariance for the CSI and focal groups. RESULTS: PRT (n = 58) and XRT (n = 30) subgroups were similar on gender (66% male), age at RT (median = 6.5 years), age at follow-up (median = 14.6 years), and government assistance status (32%). PRT and XRT focal groups differed on follow-up interval, shunt history, and total RT dose (all p < .05), whereas PRT and XRT CSI groups differed on follow-up interval, baseline neurocognitive performance score, boost volume, and CSI dose (all p < .05). The PRT focal group outperformed the XRT focal group on inhibition/switching (p = .04). The PRT CSI group outperformed the XRT CSI group on inattention/impulsivity (both p < .05). Several clinical variables (i.e., RT dose, boost field, baseline performance) predicted neurocognitive outcomes (all p < .05). The PRT focal group performed comparably to population means on most neurocognitive measures, while both CSI groups performed below expectation on multiple measures. The XRT CSI group was most impaired. All groups fell below expectation on processing speed, fine motor, and academic fluency (most p < .01). CONCLUSIONS: Findings suggest generally favorable neurocognitive and academic long-term outcomes following focal PRT. Impairment was greatest following CSI regardless of modality. Dosimetry and baseline characteristics are important determinants of outcome alone or in combination with modality.

Regulation of TGFß Signalling by TRPV4 in Chondrocytes.

The growth factor TGFß and the mechanosensitive calcium-permeable cation channel TRPV4 are both important for the development and maintenance of many tissues. Although TRPV4 and TGFß both affect core cellular functions, how their signals are integrated is unknown. Here we show that pharmacological activation of TRPV4 significantly increased the canonical response to TGFß stimulation in chondrocytes. Critically, this increase was only observed when TRPV4 was activated after, but not before TGFß stimulation. The increase was prevented by pharmacological TRPV4 inhibition or knockdown and is calcium/CamKII dependent. RNA-seq analysis after TRPV4 activation showed enrichment for the TGFß signalling pathway and identified JUN and SP1 as key transcription factors involved in this response. TRPV4 modulation of TGFß signalling represents an important pathway linking mechanical signalling to tissue development and homeostasis.

miR-324-5p is up regulated in end-stage osteoarthritis and regulates Indian Hedgehog signalling by differing mechanisms in human and mouse.

The Hedgehog (Hh) signalling pathway plays important roles during embryonic development and in adult tissue homeostasis, for example cartilage, where its deregulation can lead to osteoarthritis (OA). microRNAs (miRNAs) are important regulators of gene expression, and have been implicated in the regulation of signalling pathways, including Hh, thereby impacting upon development and disease. Our aim was to identify the function of miRNAs whose expression is altered in OA cartilage. Here we identified an increase in miR-324-5p expression in OA cartilage and hypothesised that, as in glioma, miR-324-5p would regulate Hh signalling. We determined that miR-324-5p regulates osteogenesis in human mesenchymal stem cells (MSCs) and in mouse C3H10T1/2 cells. Luciferase reporter assays demonstrated that miR-324-5p directly regulated established targets GLI1 and SMO in human but not in mouse, suggesting species-dependent mechanism of Hh pathway regulation. Stable Isotope Labelling with Amino acids in Cell culture (SILAC), mass spectrometry and whole genome transcriptome analysis identified Glypican 1 (Gpc1) as a novel miR-324-5p target in mouse, which was confirmed by real-time RT-PCR, immunoblotting and 3'UTR-luciferase reporters. Knockdown of Gpc1 reduced Hh pathway activity, and phenocopied the effect of miR-324-5p on osteogenesis, indicating that miR-324-5p regulates Hh signalling in mouse via direct targeting of Gpc1. Finally, we showed that human GPC1 is not a direct target of miR-324-5p. Importantly, as well as identifying novel regulation of Indian Hedgehog (Ihh) signalling, this study demonstrates how a miRNA can show conserved pathway regulation in two species but by distinct mechanisms and highlights important differences between human diseases and mouse models.

Positive Psychological Factors are Linked to Successful Cognitive Aging Among Older Persons Living with HIV/AIDS.

We aimed to characterize successful cognitive aging (SCA) among older HIV-infected (HIV+) and HIV-uninfected (HIV-) adults, and to determine associations with positive psychological factors and health-related quality of life (HRQoL). Ninety-nine HIV+ and 46 HIV- older adults (≥ 50 years) completed measures of neurocognition, positive psychological factors, and HRQoL. Using study-defined SCA criteria (i.e., no cognitive or everyday impairment or major depressive disorder), we compared positive psychological factors and HRQoL across four groups: HIV+/SCA+, HIV+/SCA-, HIV-/SCA+, HIV-/SCA-. SCA was identified in 29% of the HIV+ sample compared to 61% of the HIV- sample (p < 0.01). HIV+/SCA+ participants had higher scores on 8 of 10 measures of positive psychological factors as well as better HRQoL (ps < 0.05) as compared to the HIV+/SCA- group. Furthermore, the HIV+/SCA+ participants had comparable scores on these factors as HIV- adults. Fewer HIV+ than HIV- participants met SCA criteria; however, the level of positive psychological factors among the HIV+/SCA+ group was comparable to the HIV- sample. Our findings present opportunities for interventions to optimize positive psychological factors and potentially improve SCA among older HIV+ adults.

RESUMEN: Nuestro objetivo fue caracterizar el envejecimiento cognitivo exitoso (ECE) entre personas mayores VIH+ y VIH−, y determinar asociaciones con factores psicológicos positivos y con la calidad de vida relacionada a la salud (CVrS). Noventa y nueve personas mayores (de 50 años o más) VIH+ y 46 VIH− completaron indicadores de neurocognición, de factores psicológicos positivos y de CVrS. Mediante la utilización de criterios de ECE definidos por el presente estudio (p. ej. la ausencia de deterioro cognitivo, impedimentos en el funcionamiento cotidiano, o trastorno depresivo mayor) comparamos los factores psicológicos positivos y la CVrS entre cuatro grupos: VIH+/ECE+, VIH+/ECE−, VIH−/ECE+, VIH−/ECE−. El ECE fue identificado en 29% de la muestra de VIH+ comparado con 61% de la muestra de VIH− (p < 0,01). Los participantes VIH+/ECE+ obtuvieron puntuaciones más altas en 8 de los 10 indicadores de factores psicológicos positivos, así como mejor CVrS (ps < 0,05), comparado con el grupo VIH+/ECE−. Además, los participantes VIH+/ECE+ obtuvieron valores comparables a los de los adultos VIH− en estos factores. Una proporción menor de participantes VIH+ que VIH− cumplieron criterios de ECE; sin embargo, el nivel de los factores psicológicos positivos en el grupo VIH+/ECE+ fue comparable a la muestra de la población VIH−. Nuestros resultados presentan oportunidades de intervención para optimizar los factores psicológicos positivos y potencialmente mejorar el ECE entre los adultos mayores con VIH.

Effect of Patiromer on Hyperkalemia Recurrence in Older Chronic Kidney Disease Patients Taking RAAS Inhibitors.

BACKGROUND: Older people are predisposed to hyperkalemia because of impaired renal function, comorbid conditions, and polypharmacy. Renin-angiotensin-aldosterone system inhibitors (RAASi), which are recommended to treat chronic kidney disease and heart failure augment the risk. Patiromer, a nonabsorbed potassium binder, was shown in the phase 3 OPAL-HK study to decrease serum potassium in patients with chronic kidney disease taking RAASi. We studied the efficacy and safety of patiromer in a prespecified subgroup of patients aged ≥65 years from OPAL-HK. METHODS: Chronic kidney disease patients with mild or moderate-to-severe hyperkalemia received patiromer, initially 8.4 g/d or 16.8 g/d, respectively, for 4 weeks (treatment phase, part A). Eligible patients entered an 8-week randomized withdrawal phase (part B) and continued patiromer or switched to placebo. RESULTS: Mean ± standard error change in serum potassium from baseline to week 4 of part A (primary endpoint) in patients aged ≥65 years was -1.01 ± 0.05 mEq/L (P < .001); 97% achieved serum potassium 3.8-<5.1 mEq/L. The serum potassium increase during the first 4 weeks of part B was greater in patients taking placebo than in those taking patiromer (P < .001). Fewer patients taking patiromer (30%) than placebo (92%) developed recurrent hyperkalemia (serum potassium ≥5.1 mEq/L). Mild-to-moderate constipation occurred in 15% (part A) and 7% (part B) of patients aged ≥65 years. Serum potassium <3.5 mEq/L and serum magnesium <1.4 mg/dL were infrequent (4% each in patients aged ≥65 years in part A). CONCLUSIONS: Patiromer reduced recurrent hyperkalemia and was well tolerated in older chronic kidney disease patients taking RAASi.

Prospective memory in youth with perinatally-acquired HIV infection.

Youth with perinatal HIV infection (PHIV) are at increased risk for neurocognitive impairment (NCI). Prospective memory (PM) is a complex neurocognitive function that has been shown to be impaired in adults with HIV disease and independently associated with poorer daily living skills, including medication nonadherence. The current study sought to determine the presence and extent of PM deficits in youth with PHIV. Participants included 173 youth with PHIV and 85 youth perinatally HIV-exposed but uninfected (PHEU), mean age 14.1 years, 75% black, 18% Hispanic. Among youth with PHIV, 26% had a past AIDS-defining condition (Centers for Disease Control and Prevention [CDC], Class C), 74% did not (non-C). Adjusted generalized estimating equation models were used to compare groups (PHIV/C, PHIV/non-C, and PHEU) on the Naturalistic Event-Based Prospective Memory Test (NEPT) and the Prospective Memory Assessment for Children & Youth (PROMACY). Secondarily, subgroups defined by HIV serostatus and global NCI were compared (PHIV/NCI, PHIV/non-NCI, PHEU). PHIV/C had significantly lower NEPT scores than PHEU, with decreases of 40% in mean scores, but did not differ from PHIV/non-C. PHIV/NCI had 11-32% lower PROMACY scores and 33% lower NEPT scores compared to PHIV/non-NCI (all p < .05); significantly, lower scores for PHIV/NCI versus PHEU also were observed for PROMACY and NEPT indices. Findings suggest a subset of youth with PHIV (those with a prior AIDS-defining diagnosis) is vulnerable to PM deficits. The extent to which PM deficits interfere with development and maintenance of independent living and health-related behaviors during transition to adulthood requires further study.

Is the Newest Vital Sign a Useful Measure of Health Literacy in HIV Disease?

BACKGROUND: Limited health literacy is common among persons infected with HIV and has been linked to poor mental and physical health outcomes, but there are no well-validated screening measures of health literacy in this vulnerable clinical population. The present study evaluates the usefulness of the Newest Vital Sign (NVS) as a brief measure of health literacy in HIV disease. METHODS: Seventy-eight HIV+ adults were administered the NVS, Rapid Estimate of Adult Literacy in Medicine (REALM), and Single Item Literacy Screener (SILS). Main criterion variables included plasma HIV viral load, medication management capacity, self-efficacy for medication management, and perceived relationships with healthcare providers. RESULTS: The NVS showed good internal consistency and moderate correlations with the REALM and SILS. Rates of limited health literacy were highest on the NVS (30.3%) as compared to SILS (6.6%) and REALM (9.2%). A series of regressions controlling for education showed that the NVS was incrementally predictive of viral load, medication management capacity and self-efficacy, and relationships with healthcare providers, above and beyond the REALM and SILS. CONCLUSION: The NVS shows evidence of reliability, convergent validity, and incremental criterion-related validity and thus may serve as useful screening tool for assessing health literacy in HIV disease.

Accelerated and accentuated neurocognitive aging in HIV infection.

There is debate as to whether the neurocognitive changes associated with HIV infection represent an acceleration of the typical aging process or more simply reflect a greater accentuated risk for age-related declines. We aimed to determine whether accelerated neurocognitive aging is observable in a sample of older HIV-infected individuals compared to age-matched seronegatives and older old (i.e., aged ≥65) seronegative adults. Participants in a cross-sectional design included 48 HIV-seronegative (O-) and 40 HIV-positive (O+) participants between the ages of 50-65 (mean ages = 55 and 56, respectively) and 40 HIV-seronegative participants aged ≥65 (OO-; mean age = 74) who were comparable for other demographics. All participants were administered a brief neurocognitive battery of attention, episodic memory, speeded executive functions, and confrontation naming (i.e., Boston Naming Test). The O+ group performed more poorly than the O- group (i.e., accentuated aging), but not differently from the OO- on digit span and initial recall of a supraspan word list, consistent with an accelerating aging profile. However, the O+ group's performance was comparable to the O- group on all other neurocognitive tests (ps > 0.05). These data partially support a model of accelerated neurocognitive aging in HIV infection, which was observed in the domain of auditory verbal attention, but not in the areas of memory, language, or speeded executive functions. Future studies should examine whether HIV-infected adults over 65 evidence accelerated aging in downstream neurocognitive domains and subsequent everyday functioning outcomes.

Random Number Generation in HIV Disease: Associations with Neuropsychological Functions and Activities of Daily Living.

OBJECTIVE: HIV is associated with frontostriatal dysregulation and executive dysfunction. This study evaluated whether HIV-infected individuals evidence deficits in random number generation (RNG), which is a strategic task requiring paced, rule-guided production of digits. METHOD: In total, 74 HIV+ adults and 54 seronegative comparison participants completed a comprehensive research neuropsychological battery. Participants produced a random digit sequence by avoiding any order and using numbers 1 through 10 for 100 s at a pace of 1 digit/s. Outcomes included intrusions, repetitions, seriation (1-2-3-4), and cycling (median length of gaps between repeating digits). RESULTS: HIV disease was associated with higher levels of seriation and cycling (ps < .05) but not intrusions or repetitions (ps > .10). Among HIV+ individuals, higher seriation was associated with neuropsychological performance including poorer auditory attention, verbal learning, and delayed memory, whereas higher cycling scores were associated with poorer delayed memory and verbal fluency (ps < .05). Higher seriation also was independently associated with self-reported declines in activities of daily living (ADLs) in the HIV+ group. CONCLUSIONS: Individuals living with HIV disease evidence moderate difficulties in inhibiting statistically unlikely non-random sequences, which showed medium associations with higher order verbal abilities and may contribute to greater declines in everyday functioning outcomes. Future studies might examine RNG's role in health behaviors such as medical decision-making or medication adherence.

A comparison of the sensitivity, stability, and reliability of three diagnostic schemes for HIV-associated neurocognitive disorders.

HIV-associated neurocognitive disorders (HAND) occur in approximately 50% of HIV-infected individuals, yet available diagnostic criteria yield varying prevalence rates. This study examined the frequency, reliability, and sensitivity to everyday functioning problems of three HAND diagnostic criteria (DSM-5, Frascati, Gisslén). Participants included 361 adults with HIV disease and 199 seronegative adults. Neurocognitive status as defined by each of the three diagnostic systems was determined via a comprehensive neuropsychological battery. Everyday functioning was evaluated through self-report and clinician ratings. Results of logistic regressions revealed an association of HIV serostatus with Frascati-defined neurocognitive impairment (p = .027, OR = 1.7[1.1, 2.7]), but not DSM-5 or Gisslén-defined criteria (ps > .05). Frascati and DSM-5 criteria demonstrated agreement on 71% of observations, Frascati and Gisslén showed agreement on 80%, and DSM-5 and Gisslén criteria showed agreement on 46%, though reliability across the three criteria was poor. Only Frascati-defined neurocognitive impairment significantly predicted everyday functioning problems (p = .002, OR = 2.3[1.4, 3.8]). However, when both neurocognitive and complaint criteria were considered, the DSM-5 guidelines demonstrated significant relationships to everyday functioning, serostatus, and also increased reliability overtime compared to neurocognitive criteria alone (all ps < .05). A subset (n = 118) of the HIV+ group was assessed again after 14.0 (2.2) months. DSM-5 criteria evidenced significantly higher rates of incident neurocognitive disorder compared to both Frascati (p = .003) and Gisslén (p = .021) guidelines, while there were fewer remitting neurocognitive disorder diagnoses when Gisslén criteria were applied to the study sample compared to Frascati (p = .04). Future studies should aim to identify gold standard biological markers (e.g., neuropathology) and clinical outcomes associated with specific diagnostic criteria.