Search

Structural brain abnormalities, including those in white matter (WM), remain common in people with HIV (PWH). Their pathogenesis is uncertain and may reflect multiple etiologies. Oxidative stress is associated with inflammation, HIV, and its comorbidities. The post-translational carbonylation of proteins results from oxidative stress, and circulating protein carbonyls may reflect this. In this cross-sectional analysis, we evaluated the associations between protein carbonyls and a panel of soluble biomarkers of neuronal injury and inflammation in plasma (N = 45) and cerebrospinal fluid (CSF, n = 32) with structural brain MRI. The volume of abnormal WM was normalized for the total WM volume (nAWM). In this multisite project, all regression models were adjusted for the scanner. The candidate covariates included demographics, HIV disease characteristics, and comorbidities. Participants were PWH on virally suppressive antiretroviral therapy (ART) and were mostly white (64.4%) men (88.9%), with a mean age of 56.8 years. In unadjusted analyses, more nAWM was associated with higher plasma protein carbonyls (p = 0.002) and higher CCL2 (p = 0.045). In the adjusted regression models for nAWM, the association with plasma protein carbonyls remained significant (FDR p = 0.018). Protein carbonyls in plasma may be a valuable biomarker of oxidative stress and its associated adverse health effects, including within the central nervous system. If confirmed, these findings would support the hypothesis that reducing oxidative stress could treat or prevent WM injury in PWH. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: People with HIV (PWH) are more likely to experience depression, a highly morbid disease. More evidence is needed to better understand mechanisms of depression in PWH. We evaluated a panel of blood biomarkers in relation to depression symptoms in the Multicenter AIDS Cohort Study (MACS). Setting: Four sites in the United States. Methods: A cross-sectional analysis was performed within the MACS, a prospective study of cisgender men with and without HIV. Depression was assessed with the Center for Epidemiological Studies-Depression Scale, and six blood biomarkers were measured: GlycA, high sensitivity C-reactive protein (CRP), interleukin-6, CCL2, soluble CD14 (sCD14), and soluble CD163 (sCD163). Using univariable and multivariable logistic regression, the biomarkers and other factors were evaluated in relation to significant depression symptoms (SDS) by Center for Epidemiological Studies-Depression score ≥16. Results: 784 men were analyzed; most of whom (63%) were PWH. PWH were more likely to have SDS (32% vs. 21%). In univariable analysis, higher GlycA, CRP, and sCD163 concentrations were associated with SDS. In multivariable analysis, however, only higher sCD163 concentration was associated with SDS (odds ratio = 2.30, 95% CI = 1.11 to 4.76). This relationship was driven by the PWH group (odds ratio = 2.72, 95% CI = 1.12 to 6.58) and remained significant when controlling for antidepressant use. Lack of college education was also associated with SDS. Conclusions: Higher sCD163, a marker of macrophage activation, was significantly associated with significant depression symptoms in the MACS. Further research on this biomarker and macrophage activation in general is warranted to better understand and treat depression in PWH. [ABSTRACT FROM AUTHOR]

Background: Cognitive complications persist in persons with HIV during suppressive antiretroviral therapy (ART). Low levels of HIV during ART could contribute to these complications. In this study, we measured cerebrospinal fluid (CSF) HIV using a single-copy assay (SCA) to investigate a possible relationship between low-level HIV and cognition. Design/Methods: SCA data were analyzed from 3 consecutively paired CSF-plasma specimens collected over a mean of 456 days from 96 participants on suppressive ART. Using mixed models, the presence of CSF HIV by SCA as a risk factor for worse neurocognitive performance was examined. Results: At baseline on the SCA, 45.8% of participants had detectable plasma HIV RNA (median 8 copies/mL and interquartile range = 3-17 among detectable values) and 17.7% had detectable CSF HIV RNA (median CSF concentration= 3 copies/mL and interquartile range= 2-13 among detectable values). The frequency of CSF HIV RNA detection declined over time in CSF (P = 0.018) with a trend toward decline in plasma (P = 0.064). Detectable CSF HIV RNA during the study was associated with worse performance in the domains of recall (P = 0.014) and motor (P = 0.040) and a trend with worse overall global performance (P = 0.078). Integrase inhibitor use, although very infrequent in this cohort, was associated with better performance in 2 domains. Conclusions: Low-level CSF HIV RNA declines with time but is associated with worse cognitive performance in 2 domains. Addi Additional research is needed to better understand the relationship between HIV RNA persistence during long-term ART and central nervous system complications in persons with HIV. [ABSTRACT FROM AUTHOR]

Background: Across many settings, lack of virologic control remains common in people with HIV (PWH) because of late presentation and lack of retention in care. This contributes to neuronal damage and neurocognitive impairment, which remains prevalent. More evidence is needed to understand these outcomes in both PWH and people without HIV (PWOH). Methods: We recruited PWH initiating antiretroviral therapy and PWOH at 2 sites in the United States. One hundred eight adults were enrolled (56 PWOH and 52 PWH), most of whom had a second assessment at least 24 weeks later (193 total assessments). Tumor necrosis factor alpha, monocyte chemotactic protein-1 (MCP-1), neopterin, soluble CD14, and neurofilament light chain protein (NFL) were measured in plasma and cerebrospinal fluid (CSF). Using multivariate models including Bayesian model averaging, we analyzed factors associated with global neuropsychological performance (NPT-9) and CSF NFL at baseline and over time. Results: At baseline, higher CSF MCP-1 and plasma sCD14 were associated with worse NPT-9 in PWH, while CSF HIV RNA decrease was the only marker associated with improved NPT-9 over time. Among PWH, higher CSF neopterin was most closely associated with higher NFL. Among PWOH, higher CSF MCP-1 was most closely associated with higher NFL. After antiretroviral therapy initiation, decrease in CSF MCP-1 was most closely associated with NFL decrease. Conclusion: Monocyte-associated CSF biomarkers are highly associated with neuronal damage in both PWH and PWOH. More research is needed to evaluate whether therapies targeting monocyte-associated inflammation may ameliorate HIV-associated neurobehavioral diseases. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study uses Leader-Member Exchange theory to explore the associations between contact frequency (CF) of nurse leaders and their team members, leader-member relationship, and patient safety culture. BACKGROUND: Leader-member relationships are an important part of patient safety culture development. The behaviors of leaders to achieve these relationships are unknown. This study explores CF as a leader behavior to improve patient safety culture. METHODS: Cross-sectional survey of bedside nurses (N = 746) from an 8-hospital system. RESULTS: A significant association was found between relationship strength and patient safety culture; CF's effect on relationship and patient safety culture was demonstrated. CONCLUSION: Contact frequency may support relationships between leaders and members and improve patient safety culture on nursing units. Future studies should explore factors that could be enhancing and limiting CF. [ABSTRACT FROM AUTHOR]

Abstract While human immunodeficiency virus (HIV) infection has become a treatable disease with the development of combination antiretroviral therapy (cART), chronic inflammation that affects the central nervous system and other organs is still common. Reliable methods are needed to study HIV-associated inflammatory biomarkers. In this study involving both plasma and cerebrospinal fluid (CSF), we compared multiplex bead array (MBA) to a relatively new technology based on microfluidics and glass nanoreactor (GNR) technology for the measurement of three commonly studied markers from HIV-infected individuals. We found that results correlated between the two platforms for MCP-1 in both fluids as well as for plasma TNFα (all p <.005). However, results between the two platforms did not correlate for CSF TNFα or fractalkine from plasma or CSF. A statistically significant decrease in CSF TNFα over time (p <.0001) was only detectable with the MBA platform, and TNFα on the MBA was the only CSF biomarker to correlate with CSF HIV RNA (rho = 0.71, p <.0001). Meanwhile, the GNR platform was superior in terms of intra-assay fractalkine (FKN) variability and the detection of a significant FKN decrease over time. Additionally, the only significant correlation between blood biomarkers and plasma HIV RNA was with FKN on the GNR platform (rho = 0.38, p =.015). Given the variability in results between platforms, more research is needed on methods to quantitate HIV-associated inflammation. Graphical abstract Unlabelled Image Highlights • Plasma and CSF MCP-1 concentrations and plasma TNFα concentrations correlated significantly between MBA and GNR platforms. • The MBA platform was more sensitive for the quantitation of CSF TNFα, particularly for decrease over time. • The GNR platform was more precise for the quantitation of fractalkine, including decrease over time. [ABSTRACT FROM AUTHOR]

HIV-associated neurocognitive disorder (HAND) persists in the combination antiretroviral therapy (cART) era and is associated with diminished quality of life. The disorder remains challenging to diagnose given the requirement for comprehensive neuropsychological testing. Blood biomarkers are needed to facilitate the diagnosis of HAND and to gauge neurological response to antiretroviral therapy. We performed a study of plasma neurofilament light chain (NFL) that included 37 HIV-infected and 54 HIV-negative adults. In the univariate mixed-effect model involving HIV-infected participants, there was a statistically significant linear relationship between composite neuropsychological score (NPT-11) and plasma NFL (slope = − 9.9, standard error = 3.0 with 95% confidence interval − 3.2 to − 16.6 and p = 0.008 when testing slope = 0). Similarly, in the multivariate mixed-effect model, higher plasma NFL was significantly associated with worse NPT-11 (slope = − 11.5, standard error = 3.3 with 95% confidence interval − 3.7 to − 19.0 and p = 0.01 when testing slope = 0). The association between NPT-11 and NFL appeared to be driven by the group of individuals off cART. In a subset of participants who had visits before and after 24 weeks on cART (n = 11), plasma NFL declined over time (median = 22.7 versus 13.4 pg/ml, p = 0.02). In contrast, plasma NFL tended to increase over time among HIV-negative participants (median 10.3 versus 12.6 pg/ml, p = 0.065, n = 54). Plasma NFL therefore shows promise as a marker of neuropsychological performance during HIV. Larger studies are needed to determine if NFL could serve as a diagnostic tool for HAND during suppressive cART. [ABSTRACT FROM AUTHOR]

New tools are needed to understand human immunodeficiency virus central nervous system involvement. Testing 15 cerebrospinal fluid (CSF) samples for p24 antigen, using a high-sensitivity assay, we found a strong correlation trend between CSF p24 concentration and worse neuropsychological performance. [ABSTRACT FROM AUTHOR]

There is mounting evidence that prospective memory (PM) is impaired during HIV infection despite treatment. In this prospective study, 66 adults (43 HIV+ and 23 HIV negative) underwent PM assessment and cerebrospinal fluid (CSF) examination. HIV+ participants had significantly lower PM but significantly higher CSF concentrations of CXCL10 and quinolinic acid (QUIN). Higher CSF phosphorylated Tau (pTau) was associated with worse PM. In a secondary analysis excluding outliers, higher QUIN correlated with higher pTau. CSF QUIN is thus elevated during HIV infection despite antiretroviral therapy and could indirectly contribute to impaired PM by influencing the formation of pTau. [ABSTRACT FROM AUTHOR]

The soluble membrane attack complex (sMAC) represents the terminal product of the complement cascade. We enrolled 47 HIV + adults (12 of whom underwent a second visit at least 24 weeks after starting therapy) as well as 11 HIV negative controls. At baseline, cerebrospinal fluid (CSF) sMAC was detectable in 27.7% of HIV + individuals. CSF sMAC correlated with CSF HIV RNA levels and was more likely to be detectable in HIV + individuals on cART compared to HIV negative controls. In HIV + participants, there were negative association trends between sMAC and neurocognitive performance but these did not reach statistical significance. [ABSTRACT FROM AUTHOR]

HIV-associated neurocognitive disorders (HANDs) continue to be common and are associated with increased morbidity and mortality. However, the underlying mechanisms in the combination antiretroviral therapy (cART) era are not fully understood. Interferon alpha (IFNα) is an antiviral cytokine found to be elevated in the cerebrospinal fluid (CSF) of individuals with advanced HIV-associated dementia in the pre-cART era. In this cross-sectional study, we investigated the association between IFNα and neurocognitive performance in ambulatory HIV-infected individuals with milder impairment. An eight-test neuropsychological battery representing six cognitive domains was administered. Individual scores were adjusted for demographic characteristics, and a composite neuropsychological score (NPT-8) was calculated. IFNα and CSF neurofilament light chain (NFL) levels were measured using enzyme-linked immunosorbent assay (ELISA). There were 15 chronically infected participants with a history of significant immunocompromise (median nadir CD4+ of 49 cells/μl). Most participants were neurocognitively impaired (mean global deficit score of 0.86). CSF IFNα negatively correlated with three individual tests (Trailmaking A, Trailmaking B, and Stroop Color-Word) as well as the composite NPT-8 score ( r = −0.67, p = 0.006). These negative correlations persisted in multivariable analyses adjusting for chronic hepatitis B and C. Additionally, CSF IFNα correlated strongly with CSF NFL, a marker of neuronal damage (rho = 0.748, p = 0.0013). These results extend findings from individuals with severe HIV-associated dementia in the pre-cART era and suggest that IFNα may continue to play a role in HAND pathogenesis during the cART era. Further investigation into the role of IFNα is indicated. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Given the high prevalence of HIV-associated neurocognitive disorders (HAND), we examined the performance of a novel computerized cognitive assessment device (NCAD) for the evaluation of neurocognitive impairment in the setting of HIV. In addition to a standard 8-test neuropsychological battery, each participant underwent testing with the NCAD, which requires approximately 20 min and has been shown to accurately measure neurocognition in elderly individuals. The NCAD yields seven subtest scores in addition to an overall predictive score that is calculated based on subtest results. Thirty-nine HIV-infected participants were included in this study; the majority of which (71.8 %) had undetectable plasma HIV RNA levels and a history of significant immunocompromise (median nadir CD4+ count 34 cells/μl). The mean composite neuropsychological score (NPT-8) was 46.07, and mean global deficit score (GDS) was 0.59. NCAD total subtest accuracy correlated significantly with NPT-8 (Pearson correlation r = 0.59, p < 0.0001) as well as GDS (Spearman's rho = −0.36, p = 0.02). NCAD predictive score also correlated significantly with NPT-8 (Spearman's rho = −0.5601, p = 0.0016) and GDS (Spearman's rho = 0.45, p = 0.0144). When using the most recent nosology of HAND criteria for neurocognitive impairment, the area under the curve (AUC) for NCAD total subtest accuracy was 0.7562 ( p = 0.012), while the AUC for the HIV dementia scale was 0.508 ( p = 0.930). While not as comprehensive as a full neuropsychological battery, the NCAD shows promise as a rapid screening tool for HIV-infected individuals, and additional research of this device is indicated. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) persist despite combination antiretroviral therapy (cART), supporting the need to better understand HIV neuropathogenesis. Magnetic resonance spectroscopy (MRS) of the brain has demonstrated abnormalities in HIV-infected individuals despite cART. We examined the associations between MRS metabolites and selected cerebrospinal fluid (CSF) biomarkers reflecting monocyte/macrophage activation and chemotaxis. A multicenter cross-sectional study involving five sites in the USA was conducted. The following CSF biomarkers were measured: soluble CD14 (sCD14), monocyte chemotactic protein-1 (MCP-1), interferon inducible protein 10 (IP-10), and stromal cell-derived growth factor 1 alpha (SDF-1α). The following MRS metabolites were measured from basal ganglia (BG), frontal white matter (FWM), and frontal gray matter (FGM): N-acetylaspartate (NAA), myo-inositol (MI), choline (Cho), and creatine (Cr). CSF biomarkers were compared to absolute MRS metabolites as well as metabolite/Cr ratios using linear regression. Eighty-three HIV-infected individuals were included, 78 % on cART and 37 % with HAND. The most robust positive correlations were between MCP-1 and Cho in BG ( R 0.179, p < 0.001) as well as MCP-1 and MI in FWM ( R 0.137, p = 0.002). Higher Cr levels in FWM were associated with MCP-1 ( R 0. 075, p = 0.01) and IP-10 ( R 0.106, p = 0.003). Comparing biomarkers to MRS metabolite/Cr ratios impacted some relationships, e.g., higher sCD14 levels were associated with lower Cho/Cr ratios in FGM ( R 0.224, p < 0.001), although higher MCP-1 levels remained associated with Cho/Cr in BG. These findings provide evidence that monocyte activation and chemotaxis continue to contribute to HIV-associated brain abnormalities in cART-treated individuals. [ABSTRACT FROM AUTHOR]

We sought to examine the course of adherence and cognition in HIV-infected individuals with either cocaine or heroin dependence and investigate independent predictors of cognition change. A prospective study over six months was undertaken in which adherence was measured by monthly electronic pill cap monitoring (Medication Event Monitoring System), while a comprehensive neuropsychological battery resulting in a composite score (NPZ8) was performed at baseline and six months. Multivariable regression models were performed in order to determine independent associations with change in cognition. There were 101 subjects at baseline, of whom 62% were male and 83% were non-Hispanic black. 46.6% of subjects at baseline had completed high school, 36.6% reported active cocaine use during the course of the study, and 0% reported active heroin use during the course of the study. 66 subjects completed the final cognitive assessment at six months. Subjects had markedly impaired cognitive function at baseline (NPZ8 –1.49) which persisted at six months (NPZ8 –1.47) in the group of study completers. There was an average monthly decrease in adherence of –2.91% overall (p= 0.008). In the multivariable model, each of the following variables: baseline cognition (R2change = 0.121,p= 0.006), cocaine use during the study (R2change = 0.059,p= 0.046), and monthly adherence change (R2change = 0.078,p= 0.018) independently contributed to NPZ8 change with an overallR2change = 0.219 (p= 0.001). This study shows an overall decrease in adherence over time in this population of subjects with a history of drug dependence. Active cocaine use, baseline cognition, and temporal adherence changes independently contributed to changes in cognition. Further study on enhancing adherence, cognition, and limiting drug abuse are warranted in this subgroup of HIV-infected individuals. [ABSTRACT FROM PUBLISHER]

Objective: The predictors of Fanconi syndrome (FS) accompanied by renal function decline with use of the antiretroviral tenofovir disoproxil fumarate (TDF) have not been assessed. In addition, the natural history of renal recovery from FS after TDF discontinuation is not well-described. Design: We prospectively enrolled HIV-infected patients receiving TDF with newly identified FS (defined as at least two markers of proximal tubulopathy and either a >25% decline in creatinine clearance (CrCl) from pre-TDF values or a CrCl <60 mL/min in those without a known pre-TDF CrCl) in a multicenter observational study. These case participants were matched 1∶2 to controls; characteristics between the two groups were compared. Case participants with known pre-TDF CrCl values were then followed over 48 weeks to assess renal recovery. Results: Nineteen cases and 37 controls were enrolled. In multivariable analysis, previous or concurrent use of lopinavir/ritonavir [OR 16.37, 95% CI (2.28, 117.68); P = 0.006] and reduced creatinine clearance prior to initiation of TDF [OR 1.44 for every 5 mL/min reduction, 95% CI (1.09, 1.92); P = 0.012; OR 19.77 for pre-TDF CrCl lower than 83 mL/min, 95% CI (2.24, 174.67); P = 0.007] were significantly associated with FS. Of the 14 cases followed for resolution, 7 (50%) achieved at least partial resolution (defined as recovering CrCl >70% of pre-TDF values) although most participants had full normalization of proximal tubulopathy markers within two months of TDF discontinuation. Conclusions: FS, defined by specific CrCl decreases and markers of tubulopathy, is more likely in those who have received or are currently receiving concomitant lopinavir/ritonavir or who had lower CrCl prior to TDF initiation. Half of those with protocol-defined FS had CrCl recover to near pre-TDF values during the first year after TDF discontinuation. [ABSTRACT FROM AUTHOR]

To determine the indications for, rates of therapeutic anticoagulation during, and complications of warfarin therapy in HIV-infected individuals, in whom long-term anticoagulation is frequently indicated. To identify risk factors for nonoptimal anticoagulation and to determine if warfarin dosing is differentially affected by specific antiretroviral agents. Retrospective study of a dedicated anticoagulation program at one of the largest clinics for HIV-infected individuals in the United States. Seventy-three HIV-infected individuals on warfarin were followed for a total of 911 visits. The rate of therapeutic internation normalized ratio (INR) levels was 34.5% when including only visits at which patients were assessed to be adherent with warfarin. In multivariable analysis, injection drug use at baseline was an independent risk factor for subtherapeutic INR (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.3-4.7, p=0.01). Additionally, warfarin adherence was protective of both subtherapeutic (OR 0.4, 95% CI 0.2-0.6, p<0.0001) and supratherapeutic (OR 0.5, 95% CI 0.3-0.9, p=0.02) INR status. Efavirenz-based antiretroviral regimens were associated with lower weekly warfarin doses (46 mg) to maintain therapeutic INR compared to lopinavir/ritonavir-based regimens (68 mg; p=0.01) and atazanavir/ritonavir-based regimens (71 mg; p=0.007). Consistently therapeutic warfarin therapy is difficult to achieve in HIV-infected individuals, even with a dedicated anticoagulation program. Adherence to warfarin therapy is important but rates of therapeutic INR levels are nonetheless low. Lower warfarin dosing was required for efavirenz compared to two commonly used protease inhibitor-based regimens. Because of these factors, the emergence of new oral anticoagulants is an important development for HIV-infected individuals who require long term anticoagulation therapy. [ABSTRACT FROM AUTHOR]

Abstract: Encephalitis caused by cytomegalovirus (CMV) is a devastating disease that occurs mostly in profoundly immunocompromised individuals, particularly in the setting of advanced HIV infection or organ transplantation. Imaging findings in AIDS-associated cytomegalovirus encephalitis that have been described range from ventriculitis (more common) to solitary mass lesions (less common). We describe a fatal case of AIDS-associated cytomegalovirus encephalitis that included typical imaging findings but also atypical features with widespread, multifocal lesions demonstrating restricted diffusion on magnetic resonance imaging (MRI). It is likely that these diffusion abnormalities are appreciated due to changes in imaging technology from the pre-highly active antiretroviral therapy era in which the typical imaging findings of CMV encephalitis were first described. The differential diagnosis of widespread, multifocal lesions with restricted diffusion in the setting of AIDS should now include CMV encephalitis. [Copyright &y& Elsevier]

Cytomegalovirus (CMV) infection is an important cause of neurologic disease in the context of advanced human immunodeficiency virus (HIV) infection and is recognized as a cause of immune reconstitution inflammatory syndrome (IRIS) after initiation of highly active antiretroviral therapy (HAART). Central nervous system vasculitis secondary to CMV has only rarely been described in the context of HIV, despite the established ability of CMV to infect microvascular endothelial cells in the brain. However, we report a case that demonstrates the association between CMV and multiple small vessel cerebral infarct lesions after initiation of HAART. [ABSTRACT FROM AUTHOR]

We describe a case of coarctation endarteritis in an adult and review the literature pertaining to this condition. Adult coarctation endarteritis is a rare entity but often represents the initial presentation of coarctation. Diagnosis is critically important given the risk of rupture. Cardiovascular magnetic resonance imaging can be helpful in management. [ABSTRACT FROM AUTHOR]

Offers a cluster course model of education which is designed to integrate rather than separate the various academic disciplines while preserving what is unique to each. Dilemma in education; Important of the cluster course model; Seven rules of clustering that have been formulated to guide the pedagogical approach to interdisciplinary; Application of the cluster course model to achieve's Plato's second category of goodness; The future of clustering at Babson College; Conclusion.

Discusses the application of high-performance computing to the management of social science and demographic data. Description of a highly integrated system of data for minimizing technical barriers to complex data sets; Public Use Microdata Sample as one of the many data sets of sufficient size; Features of PDQ-Explore.

Surrogate markers of HIV central nervous system (CNS) persistence are needed because direct HIV measurements from the CNS require specialized protocols and are not always detectable or quantifiable. We analyzed paired plasma and CSF samples from people with HIV (PWH) on suppressive therapy (ART) with a validated HIV single copy RNA assay. Two potential markers of CNS persistence were measured (CXCL10 and sCD30). We then examined associations with CSF HIV RNA positivity in univariable and multivariable analyses. Among 66 individuals, 18.2% had detectable CSF HIV. Individuals who had detectable HIV in CSF had higher CSF CXCL10 concentrations (median 514 pg/ml versus median 317 pg/ml, p = 0.019), but did not have significantly different CSF sCD30 concentrations (median 7.5 ng/ml versus median 7.6 ng/ml, p = 0.78). In the multiple logistic analysis, both higher CSF CXCL10 (p = 0.038) and plasma HIV detectability (p = 0.035) were significantly associated with detectable CSF HIV. Both sCD30 and CXCL10 correlated positively with NfL and NSE, two neuronal markers. This study demonstrates that CSF CXCL10 concentrations reflect low level HIV CNS persistence despite virologic suppression on ART. Given that it is readily detectable and quantifiable, this chemokine may be a promising biomarker to evaluate HIV eradication therapies that target the CNS. [Display omitted] • CSF HIV was measured by single copy assay as were two CSF markers of inflammation. • CXCL10 was significantly higher among those with detectable CSF HIV RNA. • By logistic regression, CXCL10 and plasma HIV were both associated with CSF HIV. • CXCL10 and sCD30 correlated with higher concentrations of two neuronal markers. [ABSTRACT FROM AUTHOR]

Non-O1 Vibrio cholerae (NOVC) is a rare cause of septicemia in the United States. We report a case of NOVC septicemia and discuss the literature pertaining to this organism. NOVC takes on new significance given that it can be confused with toxigenic V. cholerae, a Centers for Disease Control and Prevention category B bioterrorism agent. [Copyright &y& Elsevier]

Internalized stigma, a condition characterized by negative self-stereotyping and social alienation, recently impacted the adolescents and young adults living with HIV (AYLHIV) epidemic curve and treatment adherence. While prior research has focused on the impact of internalized stigma among adults living with HIV, few studies focused on this AYLHIV. The study aims to determine internalized stigma proportion and its relationship to HIV viral suppression in AYLHIV. A cross-sectional study involved 93 fully disclosed AYLHIV receiving HIV care in Faith Alive Foundation in Jos North, Plateau State, from January to March 2023. Internalized stigma was measured using the adapted Berger HIV Stigma Scale under the domains personalized stigma (18 item questions) and negative self-image subscales (13 item questions), measured on a 4-scale of strongly disagree (1), disagree (2), agree (3), and strongly agree (4). Scores summed up to give the domain composite score with a maximum obtainable score of 72 for personalized stigma and 52 for negative self-image. A total of 93 respondents, female-63 (68%) and male-30 (32%), were involved in the study and their mean age at full disclosure was 15.7 ± 2.8 years. During the study their mean age was 19.5 ± 5.4 years, with 62% (58) ages 10–19 years and 38% (35) ages 20–26 years. Furthermore, 70% of the participants had secondary educational status, 77% had viral load results <1000 copies/ml), and 57% were on ART for up to 6 years. The average scores for personalized and negative self-image were 36.3 and 28.9, with 53% (49/93) and 52% (48/93) scoring higher than the average respectively. Further subclassification of the participants by the presence of internalized stigma domains reported 62% (58/93) with both domains, 20% (19/93) with at least one domain, and 38% (35/93) with none of the domains. Negative self-image stigma was reported more among participants 10–19 years (63%), male (31%), of secondary educational level (71%), virally unsuppressed (23%), and ≤ 6 years on ART (42%). On the other hand, personalized stigma was more among the female participants (73%), ages 20–29 years (41%), educational level (6% and 27% had primary and tertiary level of education respectively), virally suppressed (80%), and up to 6 years on ART (63%). The correlation between the internalized stigma domains and suppressed viral load using a binary multivariate regression method at 95% CI and a p-value of 0.05 was not statistically significant with personalized stigma (p = 0.73) and negative self-image (p = 0.92). The adjusted odds ratio of having internalized stigma among the virally suppressed were personalized stigmas [OR; 1.21, 95% CI; 0.42–3.47] and that of negative self-image [OR; 1.06, 95% CI; 0.38–2.95]. This study showed a high proportion of internalized stigma among females, ages 10–19 years, and virally suppressed with more odds for personalized stigma domain. However, the study reported no statistically significant association between internalized stigma domains and viral suppression. [ABSTRACT FROM AUTHOR]

Background In the Southeastern United States, the 2022 mpox outbreak disproportionately impacted people who are black and people with HIV (PWH). Methods We analyzed a cohort of 395 individuals diagnosed with mpox across 3 health care systems in Atlanta, Georgia between 1 June 2022 and 7 October 2022. We present demographic and clinical characteristics and use multivariable logistic regression analyses to evaluate the association between HIV status and severe mpox (per the US Centers for Disease Control and Prevention definition) and, among PWH, the associations between CD4+ T-cell count and HIV load with severe mpox. Results Of 395 people diagnosed with mpox, 384 (97.2%) were cisgender men, 335 (84.8%) identified as black, and 324 (82.0%) were PWH. Of 257 PWH with a known HIV load, 90 (35.0%) had > 200 copies/mL. Severe mpox occurred in 77 (19.5%) individuals and there was 1 (0.3%) death. Tecovirimat was prescribed to 112 (28.4%) people, including 56 (72.7%) people with severe mpox. In the multivariable analysis of the total population, PWH had 2.52 times higher odds of severe mpox (95% confidence interval [CI], 1.01–6.27) compared with people without HIV. In the multivariable analysis of PWH, individuals with HIV load > 200 copies/mL had 2.10 (95% CI, 1.00–4.39) times higher odds of severe mpox than PWH who were virologically suppressed. Lower CD4+ T-cell count showed a significant univariate association with severe mpox but was not found to be significantly associated with severe mpox in multivariable analysis. Conclusions PWH with nonsuppressed HIV loads had more mpox complications, hospitalizations, and protracted disease courses than people without HIV or PWH with suppressed viral loads. PWH with nonsuppressed HIV loads who are diagnosed with mpox warrant particularly aggressive monitoring and treatment. [ABSTRACT FROM AUTHOR]

The 2022 mpox outbreak primarily involved sexual transmission among men who have sex with men and disproportionately affected persons with human immunodeficiency virus (HIV). We examined viral dynamics and clinical features in a cohort evaluated for mpox infection at a comprehensive HIV clinic in Atlanta, Georgia. Viral DNA was found in 8 oropharyngeal and 5 anorectal specimens among 10 mpox cases confirmed by lesion swab polymerase chain reaction. Within-participant anatomic site of lowest cycle threshold (Ct) value varied, and lower Ct values were found in oropharyngeal and anorectal swabs when corresponding symptoms were present. This provides insight into mpox infection across multiple anatomic sites among people with HIV. [ABSTRACT FROM AUTHOR]

Background HIV-associated neurocognitive disorders (HANDs) remain prevalent despite antiretroviral therapy, particularly among older people with HIV (PWH). However, the diagnosis of HAND is labor intensive and requires expertise to administer neuropsychological tests. Our prior pilot work established the feasibility and accuracy of a computerized self-administered virtual reality program (DETECT; Display Enhanced Testing for Cognitive Impairment and Traumatic Brain Injury) to measure cognition in younger PWH. The present study expands this to a larger sample of older PWH. Methods We enrolled PWH who were ≥60 years old, were undergoing antiretroviral therapy, had undetectable plasma viral loads, and were without significant neuropsychological confounds. HAND status was determined via Frascati criteria. Regression models that controlled for demographic differences (age, sex, education, race/ethnicity) examined the association between DETECT's cognition module and both HAND status and Global Deficit Score (GDS) derived via traditional neuropsychological tests. Results Seventy-nine PWH (mean age, 66 years; 28% women) completed a comprehensive neuropsychological battery and DETECT's cognition module. Twenty-five (32%) had HAND based on the comprehensive battery. A significant correlation was found between the DETECT cognition module and the neuropsychological battery (r = 0.45, P <.001). Furthermore, in two separate regression models, HAND status (b = −0.79, P <.001) and GDS impairment status (b = −0.83, P <.001) significantly predicted DETECT performance. Areas under the curve for DETECT were 0.78 for differentiating participants by HAND status (HAND vs no HAND) and 0.85 for detecting GDS impairment. Conclusions The DETECT cognition module provides a novel means to identify cognitive impairment in older PWH. As DETECT is fully immersive and self-administered, this virtual reality tool holds promise as a scalable cognitive screening battery. [ABSTRACT FROM AUTHOR]

Depression is a common illness in people with HIV (PWH) and is associated with substantial morbidity and mortality. The mechanisms that underpin depression in PWH remain incompletely elucidated, and more research is therefore needed to develop effective treatments. One hypothesis is that neurotransmitter levels may be altered. These levels could be influenced by the chronic inflammation and viral persistence that occurs in PWH. We examined a panel of cerebrospinal fluid (CSF) neurotransmitters in PWH on suppressive antiretroviral therapy (ART), many of whom had a current depression diagnosis. CSF monoamine neurotransmitters and their metabolites were measured from participants in studies at the Emory Center for AIDS Research (CFAR). Only participants on stable ART with suppressed HIV RNA from both plasma and CSF were analyzed. Neurotransmitter levels were measured with high-performance liquid chromatography (HPLC). Neurotransmitters and their metabolites included dopamine (DA), homovanillic acid (HVA, a major metabolite of dopamine), serotonin (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA, a major metabolite of serotonin), and 4-hydroxy-3-methoxyphenylglycol (MHPG, a major metabolite of norepinephrine). Multivariable logistic regression was used to evaluate factors associated with depression. There were 79 PWH with plasma and CSF HIV RNA levels < 200 copies/mL at the time of the visit, and 25 (31.6%) carried a current diagnosis of depression. Participants with depression were significantly older (median age 53 years versus 47 years, P = 0.014) and were significantly less likely to be African American (48.0% versus 77.8%, P = 0.008). Participants with depression had significantly lower dopamine levels (median 0.49 ng/mL versus 0.62 ng/mL, P = 0.03) and significantly lower 5-HIAA levels (median 12.57 ng/mL versus 15.41 ng/mL, P = 0.015). Dopamine and 5-HIAA were highly correlated. In the multivariable logistic regression models, lower 5-HIAA was significantly associated with the depression diagnosis when accounting for other significant demographic factors. The associations between lower 5-HIAA, lower dopamine, and depression in PWH suggest that altered neurotransmission may contribute to these comorbid conditions. However, the effects of antidepressants on neurotransmitters cannot be ruled out as a factor in the 5-HIAA results. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) sequelae continue to be common in HIV-infected individuals despite combination antiretroviral therapy (cART). These sequelae include HIV-associated neurocognitive disorder (HAND) and virologic persistence in the CNS. Resting state functional magnetic resonance imaging (rsfMRI) is a widely used tool to examine the integrity of brain function and pathology. In this study, we examined 16 HIV-positive (HIV+) subjects and 12 age, sex, and race matched HIV seronegative controls (HIV−) whole-brain high-resolution rsfMRI along with a battery of neurocognitive tests. A comprehensive data-driven analysis of rsfMRI revealed impaired functional connectivity, with very large effect sizes in executive function, language, and multisensory processing networks in HIV+ subjects. These results indicate the potential of high-resolution rsfMRI in combination with advanced data analysis techniques to yield biomarkers of neural impairment in HIV. [ABSTRACT FROM AUTHOR]

Objective: Hearing consists of peripheral components (outer and middle ear, cochlea) and the central auditory system (cochlear nuclei to the auditory cortex). Speech perception relies on peripheral hearing abilities (i.e., pure-tone thresholds) and central auditory processing (CAP) and cognitive functioning. Specifically, working memory, executive function, attention, and verbal functioning allow for speech understanding. As a result, CAP deficits are also influenced by peripheral hearing sensitivity and cognitive functioning. Assessing CAP deficits can be difficult because of these complex interactions. Prior work has shown persons living with HIV (PWH) are at higher risk for sensorineural hearing loss compared to persons living without HIV (PWOH) after adjusting for age, sex, and noise exposure. Further, HIV is a risk factor for cognitive impairment, one example being Alzheimer's disease (AD) and its precursor, Mild Cognitive Impairment (MCI), with auditory dysfunction occurring in earlier stages of AD. Therefore, the purpose of this study was to evaluate: 1) the peripheral hearing sensitivity and CAP in PWH and PWOH; and 2) the association between cognitive function measures and CAP in PWH and PWOH. Participants and Methods: Participants included 59 PWH (39 men and 20 women, mean age=66.7 years [SD=4.4 years]) and 27 PWOH (13 men and 14 women, mean age=71.9 years [SD=7.1 years]). Participants completed a standard neuropsychological battery assessing the domains of learning, recall, executive function, working memory, verbal fluency, processing speed and motor. Raw scores were transformed to demographically corrected, domain T-scores. Cognitive function was normal for 39 (66.1%) PWH and 16 (59.3%) PWOH while 43 (72.9%) PWH and 17 (63.0%) PWOH were determined to have MCI. Participants with dementia were excluded. Participants also completed a hearing assessment, a portion of which consisted of pure-tone thresholds, peripheral hearing measure, and dichotic digits testing (DDT), a CAP measure. Pure-tone air-conduction thresholds were obtained at octave frequencies from 0.25 through 8 kHz, including 3 and 6 kHz. A pure-tone average (PTA) was calculated from 0.5, 1, 2, and 4 kHz thresholds for each ear. The DDT involves the presentation of numbers from 1 to 10, excluding 7, in which two different digits are presented to one ear while two other digits are simultaneously presented to the opposite ear. The outcome of DDT is percent correct. Results: PWH had slightly lower (i.e., better) mean PTAs in both ears compared to PWOH, but this was not statistically significant. Conversely, PWH had lower percent correct DDT results compared to PWOH, but this difference was also not statistically significant. Participants with impairment in verbal fluency, executive functioning, and working memory had significantly worse DDT results by approximately 10%, but only for right ear data. Conclusions: PWH in our sample had better hearing than PWOH, which can be explained by PWH having a lower mean age. PWH had poorer DDT results, however, indicative of CAP deficits rather than peripheral hearing problems. Poor right ear DDT was associated with impairments specifically in frontal-based cognitive processes with an executive component. [ABSTRACT FROM AUTHOR]

HIV-associated neurocognitive disorder (HAND) is a common condition in both developed and developing nations, but its cause is largely unknown. Previous research has inconsistently linked Alzheimer's disease (AD), viral burden, and inflammation to the onset of HAND in HIV-infected individuals. Here we simultaneously measured cerebrospinal fluid (CSF) levels of established amyloid and tau biomarkers for AD, viral copy numbers, and six key cytokines in 41 HIV-infected individuals off combination anti-retroviral therapy (14 with HAND) who underwent detailed clinical and neuropsychological characterization, and compared their CSF patterns with those from young healthy subjects, older healthy subjects with normal cognition, and older people with AD. HAND was associated with the lowest CSF levels of phosphorylated tau (p-Tau181) after accounting for age and race. We also found very high CSF levels of the pro-inflammatory interferon gamma-induced protein 10 (IP-10/CXCL10) in HIV regardless of cognition, but elevated CSF interleukin 8 (IL-8/CXCL8) only in HIV-NC but not HAND. Eleven HIV-infected subjects underwent repeat CSF collection six months later and showed strongly correlated longitudinal changes in p-Tau181 and IL-8 levels (R = 0.841). These data suggest reduced IL-8 relative to IP-10 and reduced p-Tau181 to characterize HAND. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) occurs frequently in hospitalized patients and has been associated with the administration of certain medications. Concerns have been raised in recent reports that the antibiotic combination of vancomycin and piperacillin/tazobactam (combV/P) may be more associated with AKI than monotherapy with either drug. Methods: To compare the incidence of and risk factors for AKI in patients receiving combV/P versus monotherapy with either drug, a retrospective study was conducted in non-critically ill inpatients at a large urban teaching hospital. AKI was defined as either: (1) Increase in serum creatinine ≥0.5 mg/dl OR (2) ≥1.5-fold creatinine increase from admission baseline. In addition to standard multivariable regression adjustment, propensity score weighting was used as a robust approach to reduce the effects of covariate confounding when estimating the adjusted odds of AKI. Results: A total of 228 patients were evaluated. The overall incidence of AKI was 11.8 % (27 of 228 patients). AKI occurred in 4 of 101 patients in the vanc group (4.0 %), 4 of 26 patients in the piptazo group (15.4 %), and 19 of 101 patients in the combV/P group (18.8 %). The univariable odds of AKI was significantly lower in the vanc group compared to both the combV/P group (OR 0.178, 95 % CI 0.058-0.544, p = 0.003) and piptazo (OR 0.227, 95 % CI 0.053-0.978, p = 0.047) group. A multivariable model accounting for baseline characteristics again showed that vanc monotherapy was associated with lower odds of AKI than combV/P (OR 0.14, 95 % CI 0.04-0.52, p = 0.004). Male sex was also associated with lower odds of AKI (OR 0.28, 95 % CI 0.10-0.79, p = 0.02) in the multivariable model. In the propensity score analysis using inverse probability of treatment weighting (IPTW), vanc monotherapy and male sex were again associated with lower odds of AKI (OR 0.17; 95 % CI 0.04-0.62, p = 0.008 and OR 0.28, 95 % CI 0.09-0.89, p = 0.03, respectively). Conclusion: This study substantiates recent reports that combV/P may be more associated with AKI than vanc monotherapy in hospital inpatients. AKI also appears to be more likely in females during therapy with these antimicrobials. While severity of illness is difficult to account for, these findings are further justification for narrowing antibiotic coverage when possible after this combination has been initiated in hospitalized patients. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 59-year-old man in Atlanta, Georgia proven postmortem to have antiretroviral-therapy (ART)-associated coccidioidomycosis manifesting as atypical lymphocytic meningitis. The man sought care for headache, photophobia, neck stiffness, fevers, chills, weight loss, dyspnea and cough. Results of laboratory tests, chest imaging and cerebrospinal fluid (CSF) examination are discussed.

The article discusses the case of a 45-year-old homeless woman with acquired immune deficiency syndrome (AIDS) who experienced pulmonary tuberculosis (TB) relapse with an associated resistance to antituberculous drugs isoniazid (INH) and rifampin (RIF). Her symptoms included fever, night sweats, weight loss and cough. She tested positive for Mycobacterium tuberculosis complex in August 2009, while the culture of the sputum specimen obtained at her admission indicated that the isolate was resistant to INH but susceptible to RIF. After a week, mycobacteriology laboratory findings showed that the isolate was resistant to both INH and RIF. The patient underwent injectable aminoglycoside therapy following her readmission.

We examined the relationship between CSF immune cells and neurocognition and neuronal damage in HIV+ individuals before and after initiating antiretroviral therapy. Multivariate analysis at baseline indicated that greater CD4+ T cell abundance was associated with better cognition (p =.017), while higher CSF HIV RNA was associated with increased neuronal damage (p =.014). Following 24 weeks of antiretroviral therapy, CD8+ T cells, HLA-DR expressing CD4+ and CD8+ T cells, B cells, NK cells, and non-classical monocyte percentage decreased in CSF. Female gender was negatively associated with cognitive performance over time, as was higher percentage of HLA-DR expressing CD8+ T cells at baseline. Unlabelled Image • CSF CD8+ T cells and other immune effector cells decreased after initiating ART. • Activated CSF immune cells remained more abundant in HIV+ individuals after ART. • Greater CSF CD4+ T cell abundance was associated with better cognition at baseline. • Higher CSF HIV RNA was associated with higher neurofilament light chain at baseline. • Cognitive performance over time was associated with female gender and HLA DR+ CD8+. [ABSTRACT FROM AUTHOR]

A 66-year-old man developed fever, chills, myalgias, three erythematous skin lesions, and transient left eyelid lag. Because of persistent fever, he was hospitalized 4 weeks after the onset of disease; a peripheral blood smear showed Babesia microti in 3% of his erythrocytes. Eighteen hours later, he died unexpectedly. Autopsy showed pancarditis with a diffuse lymphoplasmacytic infiltrate, and spirochetes were found in the myocardium. Antibody titers to both the Lyme disease spirochete Borrelia burgdorferi and Babesia microti were elevated. The finding of spirochetes in the myocardium and the elevated antibody titers to Borrelia burgdorferi suggest that the patient died from cardiac involvement of Lyme disease. [ABSTRACT FROM AUTHOR]