ZIKA VIRUS - The Puerto Rican Experience.

Zika has been one of the most devastating new emerging viruses epidemic due to its effects on the nervous system mostly newborns. It was an unexpected epidemic that jeopardized our population and those with the appropriate environment for the virus to replicate, the tropics. It took us by surprise and challenged our health system. When it arrived in Puerto Rico in December 2015 many questions were raised regarding how the clinical manifestations of the infection will affect our population. Although most of infections go on asymptomatic it was not clear how our population heavily infected with other arboviruses such as dengue and chikungunya will alter the clinical and neurological manifestations of Zika. Other questions regarding our health system preparedness to attend to such an epidemic was questioned. We hope that these experiences will aid in the establishment of procedures to deal with similar epidemics in the future and help to gain a better understanding of the acute and chronic effects of the infection in the clinical manifestations and possible management of the infection in a clinical and public health manner. Puerto Rico possess a special position in the Caribbean and can serve to spearhead the establishment of procedures to detect, treat, and study the effects of these new emerging virus epidemics. Thereby establishing the needed programs to attend to other similar epidemics.

In Vitro Blood-Brain Barrier Modeling adapted for Peripheral Blood Mononuclear Cell Transmigration from HIV-Positive Patients for Clinical Research on Therapeutic Drug Intervention.

OBJECTIVE: HIV-associated cognitive impairment (HACI) continues to persist for HIV-seropositive individuals who are on antiretroviral therapy (ART). HACI develops in part when HIV-infected monocytes (MOs) transmigrate through the blood-brain barrier (BBB) and secrete pro-inflammatory cytokines and chemokines, which leads to neuronal damage. In vitro BBB models are important tools that can elucidate mechanisms of MO transmigration. Previously described in vitro BBB models relied on pathology specimens, resulting in potentially variable and inconsistent results. This project reports on a reliable and consistent alternative in vitro BBB model that has the potential to be used in clinical research intervention studies analyzing the effects of ART on the BBB and on MO transmigration. METHODS: A bilayer BBB model was established with commercially available astrocytes and endothelial cells on a 3µm PET membrane insert to allow the contact of astrocytic foot processes with endothelial cells. Inserts were cultured in growth medium for 7 days before exposure to HIV- or HIV+ peripheral blood mononuclear cells (PBMCs). PBMCs were allowed to transmigrate across the BBB for 24 hours. RESULTS: Confluency and integrity measurements by trans-endothelial electrical resistance (TEER) (136.7 ± 18.3Ω/cm2) and permeability (5.64 ± 2.20%) verified the integrity of the in vitro BBB model. Transmigrated MOs and non-MOs were collected and counted (6.0x104 MOs; 1.1x105 non-MOs). Markers indicative of glial fibrillary acidic protein (GFAP), von Willebrand factor (vWF), and p-glycoprotein (Pgp) were revealed in immunofluorescence staining (IF), indicating BBB phenotype and functionality. CONCLUSION: Potential applications for this model include assessing the HIV DNA copy numbers of transmigrated cells (pre- and post-targeted ART) and understanding the role of oxidative stress related to HIV DNA and HACI.

Soluble insulin receptor as a source of insulin resistance and cognitive impairment in HIV-seropositive women.

Insulin resistance occurs in HIV-infected individuals and is associated with HIV-associated neurocognitive disorders (HAND). However, the mechanisms involved are not well understood. Previously, we showed a correlation between soluble insulin receptor (sIR) and HAND. Here, we investigated if binding of free insulin to sIR and soluble insulin-like growth factor-1 receptor (sIGF1-R) levels are associated with sIR in HAND. Thirty-four (34) HIV-seropositive women stratified by cognitive status and five HIV-seronegative women were evaluated. In a subgroup of 20 HIV positive and 5 donors, binding of plasma insulin to sIR was determined by ELISA assay of residual insulin levels in plasma immuno-depleted with anti-IR-monoclonal antibody-Sepharose beads. sIR and sIGF1-R levels were determined by ELISA. Nonparametric statistics were used. Higher percentages of insulin bound to sIR significantly correlated with sIR levels and were associated with HAND status. Higher levels of plasma sIGF1-R had a positive correlation with sIR levels (p = 0.011) and were associated with HAND (p = 0.006). No correlations were observed with age, viral-immune profile, antiretroviral therapy, or TNF. This study suggests that changes in sIGF1-R levels and insulin binding to sIR may contribute to HAND.

Validity of the Neurology Quality-of-Life (Neuro-QoL) measurement system in adult epilepsy.

Epilepsy is a chronic neurological disorder that results in recurring seizures and can have a significant adverse effect on health-related quality of life (HRQL). The Neuro-QoL measurement initiative is an NINDS-funded system of patient-reported outcome measures for neurology clinical research, which was designed to provide a precise and standardized way to measure HRQL in epilepsy and other neurological disorders. Using mixed-method and item response theory-based approaches, we developed generic item banks and targeted scales for adults and children with major neurological disorders. This paper provides empirical results from a clinical validation study with a sample of adults diagnosed with epilepsy. One hundred twenty-one people diagnosed with epilepsy participated, the majority of which were male (62%) and Caucasian (95%), with a mean age of 47.3 (SD=16.9). Baseline assessments included Neuro-QoL short forms and general and external validity measures. The Neuro-QoL short forms that are not typically found in other epilepsy-specific HRQL instruments include Stigma, Sleep Disturbance, Emotional and Behavioral Dyscontrol, and Positive Affect and Well-Being. Neurology Quality-of-Life short forms demonstrated adequate reliability (internal consistency range=.86-.96; test-retest range=.57-.89). Pearson correlations (p<.01) between Neuro-QoL forms of emotional distress (anxiety, depression, stigma) and the QOLIE-31 Emotional Well-Being subscale were in the moderate-to-strong range (r's=.66, .71 and .53, respectively), as were relations with the PROMIS Global Mental Health subscale (r's=.59, .74 and .52, respectively). Moderate correlations were observed between Neuro-QoL Social Role Performance and Satisfaction and the QOLIE-31 Social Function (r's=.58 and .52, respectively). In measuring aspects of physical function, the Neuro-QoL Mobility and Upper Extremity forms demonstrated moderate associations with the PROMIS Global Physical Function subscale (r's=.60 and .61, respectively). Neuro-QoL measures of perceived cognitive function (executive function and general concerns) produced moderate-to-strong correlations with the QOLIE-31 Cognition subscale (r's=.65 and .75, respectively) and moderate relations with the Liverpool Adverse Events Profile (r's=.51 and .69, respectively). Finally, the Neuro-QoL Fatigue measure demonstrated moderate associations with the QOLIE-31 Energy/Fatigue subscale (r=-.65), Liverpool Adverse Events Profile (r=.69), and the Liverpool Seizure Severity Scale (r=.50). Five Neuro-QoL short forms demonstrated statistically significant responsiveness to change at 5-7months, including Fatigue, Sleep Disturbance, Depression, Positive Affect and Well-Being, and Emotional and Behavioral Dyscontrol. Overall, Neuro-QoL instruments showed good evidence for internal consistency, test-retest reliability, convergent validity, and responsiveness to change over several months. These results support the validity of Neuro-QoL to measure HRQL in adults with epilepsy.

Diagnosing Alzheimer's disease: Which dementia screening test to use in elderly Puerto Ricans with mild cognitive impairment and early Alzheimer's disease?

Typically, Alzheimer's disease (AD) diagnosis is not made at its earliest period, for instance, at mild cognitive impairment (MCI) and early AD (E-AD). Our study aims to demonstrate a correlation between the screening tools, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating (CDR), and the biological biomarkers in the cerebrospinal fluid (CSF) amyloid beta 1-42 (Aß42), phosphorylated tau (p-tau) proteins and total tau (t-tau)/Aß42 ratio in Puerto Ricans > 55 years old with MCI and E-AD. We evaluated 30 participants, including demographics, memory scales, and CSF biomarkers. Twenty-eight CSF biomarkers (Aß42, p-tau protein, and t-tau/Aß42 ratio) were analyzed using the Meso Scale Discovery Platform (MSD). Associations between memory scales (MoCA, MMSE, CDR) and CSF markers were performed using Spearman rho correlation. Our study revealed a statistical association favoring a direct relationship between MMSE and MoCA with t-tau/Aß42 ratio in CSF (P = 0.022, P = 0.035, respectively). We found a trend toward significance with an inverse relationship with MMSE and Aß42 (P = 0.069) and a direct relationship with MMSE and p-tau (P = 0.098). MMSE and MoCA screening tests were identified with a statistically significant association with the CSF biomarkers, specifically t-tau/Aß42 ratio, in elderly Puerto Ricans with MCI and E-AD. Puerto Ricans > 55 years old with MCI and E-AD could be screened confidently with MMSE and MoCA for a higher likelihood of earlier detection and, thus, initiation of disease-modifying treatment and prompt non-pharmacological interventions.

Disparities in Metabolic Syndrome and Neurocognitive Function Among Older Hispanics/Latinos with Human Immunodeficiency Virus.

Neurocognitive impairment and metabolic syndrome (MetS) are prevalent in persons with HIV (PWH). We examined disparities in HIV-associated neurocognitive function between Hispanic and non-Hispanic White older PWH, and the role of MetS in explaining these disparities. Participants included 116 community-dwelling PWH aged 50-75 years enrolled in a cohort study in southern California [58 Hispanic (53% Spanish speaking) and 58 age-comparable non-Hispanic White; overall group: age: M = 57.9, standard deviation (SD) = 5.7; education (years): M = 13, SD = 3.4; 83% male, 58% AIDS, 94% on antiretroviral therapy]. Global neurocognition was derived from T-scores adjusted for demographics (age, education, sex, ethnicity, language) on a battery of 10 cognitive tests. MetS was ascertained via standard criteria that considered central obesity, and fasting elevated triglycerides, low high-density lipoprotein cholesterol and elevated glucose, or medical treatment for these conditions. Covariates examined included sociodemographic, psychiatric, substance use and HIV disease characteristics. Compared with non-Hispanic Whites, Hispanics showed worse global neurocognitive function (Cohen's d = 0.56, p < 0.05) and had higher rates of MetS (38% vs. 56%, p < 0.05). A stepwise regression model including ethnicity and significant covariates showed Hispanic ethnicity was the sole significant predictor of worse global neurocognition (B = -3.82, SE = 1.27, p < 0.01). A model also including MetS showed that both Hispanic ethnicity (B = -3.39, SE = 1.31, p = 0.01) and MetS (B = -2.73, SE = 1.31, p = 0.04) were independently associated with worse neurocognition. In conclusion, findings indicate that increased MetS is associated with worse neurocognitive function in both Hispanic and non-Hispanic White older PWH, but does not explain neurocognitive disparities. MetS remains an important target for intervention efforts to ameliorate neurocognitive dysfunction among diverse older PWH.

YWHAE/14-3-3ε: a potential novel genetic risk factor and CSF biomarker for HIV neurocognitive impairment.

YWHAE (14-3-3ε) protein levels are considered to be a reliable biomarker for neurodegeneration. The YWHAE protein interacts both directly and indirectly with human immunodeficiency virus (HIV) accessory proteins, leading to cell death. The purpose of this study was to examine the relationship between YWHAE polymorphisms and HIV-associated neurocognitive disorder (HAND) and the relationship between YWHAE protein levels and HAND. A cross-sectional study using random samples of HIV-seropositive (n = 20) and HIV-seronegative (controls) (n = 16) women from the Hispanic-Latino Longitudinal Cohort of Women was conducted. Individuals who are HIV-seropositive and heterozygous at the rs4790084/rs1204828 loci in the YWHAE gene were 3× more likely to display reduced cognitive functioning, to have received a HAND diagnosis, and to have less YHWAE protein expressed than homozygotes. Western blots from cerebral spinal fluid indicate that the HIV-seropositive women with HAND expressed 4.5× less YWHAE compared to HIV-seropositive cognitively normal women (94 % sensitivity, 84 % specificity; HIV-seropositive vs. controls). Therefore, polymorphism in YWHAE may be a genetic risk factor for HAND and levels of YWHAE protein are a likely biomarker for neurocognitive status in HIV-seropositive women.

Impact of antiretroviral therapy intensification with C-C motif chemokine receptor 5 antagonist maraviroc on HIV-associated neurocognitive impairment.

OBJECTIVES: Chemokine receptor CCR5 is the principal co-receptor for entry of M-tropic HIV virus into immune cells. It is expressed in the central nervous system and may contribute to neuro-inflammation. The CCR5 antagonist maraviroc (MVC) has been suggested to improve HIV-associated neurocognitive impairment (NCI). DESIGN: A double-blind, placebo-controlled, 48-week, randomized study of MVC vs. placebo in people with HIV (PWH) on stable antiretroviral therapy (ART) for more than one year in Hawaii and Puerto Rico with plasma HIV RNA less than 50 copies/ml and at least mild NCI defined as an overall or domain-specific neuropsychological z (NPZ) score less than -0.5. METHODS: Study participants were randomized 2 : 1 to intensification of ART with MVC vs. placebo. The primary endpoint was change in global and domain-specific NPZ modeled from study entry to week 48. Covariate adjusted treatment comparisons of average changes in cognitive outcome were performed using winsorized NPZ data. Monocyte subset frequencies and chemokine expression as well as plasma biomarker levels were assessed. RESULTS: Forty-nine participants were enrolled with 32 individuals randomized to MVC intensification and 17 to placebo. At baseline, worse NPZ scores were seen in the MVC arm. Comparison of 48-week NPZ change by arm revealed no differences except for a modest improvement in the Learning and Memory domain in the MVC arm, which did not survive multiplicity correction. No significant changes between arms were seen in immunologic parameters. CONCLUSION: This randomized controlled study found no definitive evidence in favor of MVC intensification among PWH with mild cognitive difficulties.

Translational spatial task and its relationship to HIV-associated neurocognitive disorders and apolipoprotein E in HIV-seropositive women.

HIV-associated neurocognitive disorders (HAND) continue to be a neurological complication of HIV infection in the era of combined antiretroviral therapy. Hippocampal neurodegeneration and dysfunction occurs as a result of HIV infection, but few studies to date have assesses spatial learning and memory function in patients with HAND. We used the Memory Island (MI) test to study the effects of HIV infection, apolipoprotein E (ApoE) allele status, and cerebral spinal fluid (CSF) ApoE protein levels on spatial learning and memory in our cohort of Hispanic women. The MI test is a virtual reality-based computer program that tests spatial learning and memory and was designed to resemble the Morris Water Maze test of hippocampal function widely used in rodent studies. In the current study, HIV-seropositive women (n = 20) and controls (n = 16) were evaluated with neuropsychological (NP) tests, the MI test, ApoE, and CSF ApoE assays. On the MI, the HIV-seropositive group showed significant reduced learning and delayed memory performance compared with HIV-seronegative controls. When stratified by cognitive performance on NP tests, the HIV-seropositive, cognitively impaired group performed worse than HIV-seronegative controls in ability to learn and in the delayed memory trial. Interestingly, differences were observed in the results obtained by the NP tests and the MI test for ε4 carriers and noncarriers: NP tests showed effects of the ε4 allele in HIV-seronegative women but not HIV-seropositive ones, whereas the converse was true for the MI test. Our findings suggest that the MI test is sensitive in detecting spatial deficits in HIV-seropositive women and that these deficits may arise relatively early in the course of HAND.

Soluble Insulin Receptor Levels in Plasma, Exosomes, and Urine and Its Association With HIV-Associated Neurocognitive Disorders.

Background: HIV-associated neurocognitive disorders (HAND) are one of the HIV-associated comorbidities affecting 20-50% of the people with HIV (PWH) infection. We found that the soluble insulin receptor (sIR) levels in plasma and cerebrospinal fluid (CSF) were significantly higher in HIV-infected women. The mechanism of sIR release into the plasma remains unknown, but the detection of the sIR in exosomes may uncover novel mechanisms of sIR secretion from HIV-infected cells and its contribution to HIV disease progression and HAND development. Quantification of sIR in urine may represent a less invasive and more accessible diagnostic tool. Our objective was to quantify sIR levels in plasma, plasma-derived exosomes, and urine, and evaluate their association with HAND and renal function. Methods: We measured full-length sIR in the plasma and urine of 38 controls and 76 HIV-infected women by ELISA, and sIR, HIV-1 Tat, and reactive oxygen species (ROS) in exosomes by flow cytometry. Results: Plasma and exosomes with sIR were significantly higher in HIV-infected women when compared with controls and HAND. Exosomal sIR positively correlated with exosomal ROS and exosomal HIV-1 Tat in HIV-infected women. Exosomal ROS was significantly higher in HIV-infected women with more symptomatic cognitive impairment. Plasma-derived exosomes exhibited significantly higher levels of astrocyte (GFAP) and neuronal (L1CAM) markers in HIV-infected women, confirming the presence of circulating CNS-derived exosomes in the blood of HIV-infected women. Urine sIR positively correlated with eGFR in controls, but not in HIV-infected women, regardless there was no significant difference in renal function as determined by the estimated glomerular filtration rate (eGFR, p = 0.762). In HIV-infected women, higher plasma sIR correlated with lower urine sIR that could suggest sIR retention in blood or decreased renal filtration. Discussion: Higher plasma sIR levels and their correlation with ROS in plasma-derived exosomes with HAND suggest a combined role of metabolic disturbances, oxidative stress, exosome release, and cognitive decline. Communication between CNS and periphery is compromised in PWH, thus plasma-derived exosomes may shed light on disrupted cellular mechanisms in the brain of PWH. High plasma and low urine sIR levels could suggest sIR retention in blood or decreased renal filtration.

Linguistic adaptation of the clinical dementia rating scale for a Spanish-speaking population: a focus group approach.

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia worldwide. In Hispanic populations there are few validated tests for the accurate identification and diagnosis of AD. The Clinical Dementia Rating (CDR) scale is an internationally recognized questionnaire used to stage dementia. This study's objective was to develop a linguistic adaptation of the CDR for the Puerto Rican population. METHODS: The linguistic adaptation consisted of the evaluation of each CDR question (item) and the questionnaire's instructions, for similarities in meaning (semantic equivalence), relevance of content (content equivalence), and appropriateness of the questionnaire's format and measuring technique (technical equivalence). A focus group methodology was used to assess cultural relevance, clarity, and suitability of the measuring technique in the Argentinean version of the CDR for use in a Puerto Rican population. RESULTS: A total of 27 semantic equivalence changes were recommended in four categories: higher than 6th grade level of reading, meaning, common use, and word preference. Four content equivalence changes were identified, all focused on improving the applicability of the test questions to the general population's concept of street addresses and common dietary choices. There were no recommendations for changes in the assessment of technical equivalence. CONCLUSIONS: We developed a linguistically adapted CDR instrument for the Puerto Rican population, preserving the semantic, content, and technical equivalences of the original version. Further studies are needed to validate the usefulness of the adapted CDR instrument with the staging of Alzheimer's disease in the Puerto Rican population.

Atypical presentation of basilar artery thrombosis due to hypercoagulable state and incidental patent foramen ovale: a case report.

This is a case presentation of a 31 year old woman without history of any systemic illness and on her second pregnancy. Three days after an elective cesarean delivery without complications presented with neurological deficits mainly difficulty talking that progressed to aphasia, dizziness, and loss of vision. Neuro-images showed several ischemic areas in the brain. A magnetic resonance angiogram revealed a thrombus in the basilar artery. A transesophageal echocardiogram demonstrated a patent foramen ovale (PFO). The early recognition and diagnosis of PFO is crucial in preventing long-term complications.

Brief Report: Effects of Low-Volume High-Intensity Interval Training in Hispanic HIV+ Women: A Nonrandomized Study.

BACKGROUND: Low cardiorespiratory fitness (CRF) is usually observed in people living with HIV. The effect of a low-volume high-intensity interval training (LV-HIIT) on CRF in HIV+ and HIV- Hispanic women was evaluated in this study. SETTING: A nonrandomized clinical trial with pre-test and post-test using a LV-HIIT intervention was conducted in the AIDS Clinical Trials Unit and the Puerto Rico Clinical and Translational Research Consortium at the University of Puerto Rico Medical Sciences Campus. METHODS: Twenty-nine HIV+ and 13 HIV- Hispanic women recruited from community-based programs and clinics, and able to engage in daily physical activities, volunteered to participate. Of these, 20 HIV+ (69%) and 11 HIV- (85%) completed the study and were included in the analyses. LV-HIIT consisted of 6-week, 3 d/wk, 8-10 high-intensity and low-intensity intervals on a cycle ergometer at 80%-90% of heart rate reserve. Main outcome measures were CRF (defined as VO2peak), peak workload, and time to peak exercise. RESULTS: Average peak workload and time to peak exercise increased after training (P < 0.05) in both groups. However, average CRF was significantly higher after training only in the HIV- group. Gains in CRF were observed in 100% of HIV- and 50% of HIV+ women. This was not influenced by exercise testing, habitual physical activity, or anthropometric variables. CONCLUSIONS: Given the lack of change in CRF observed in the HIV+ group after LV-HIIT intervention, it is important to focus on variations that may occur within groups.

A recombinant gp145 Env glycoprotein from HIV-1 expressed in two different cell lines: Effects on glycosylation and antigenicity.

The envelope glycoprotein (Env) of the human immunodeficiency virus (HIV), has been the primary target for the development of a protective vaccine against infection. The extensive N-linked glycosylation on Env is an important consideration as it may affect efficacy, stability, and expression yields. The expression host has been shown to influence the extent and type of glycosylation that decorates the protein target. Here, we report the glycosylation profile of the candidate subtype C immunogen CO6980v0c22 gp145, which is currently in Phase I clinical trials, produced in two different host cells: CHO-K1 and Expi293F. The amino acid sequence for both glycoproteins was confirmed to be identical by peptide mass fingerprinting. However, the isoelectric point of the proteins differed; 4.5-5.5 and 6.0-7.0 for gp145 produced in CHO-K1 and Expi293F, respectively. These differences in pI were eliminated by enzymatic treatment with sialidase, indicating a large difference in the incorporation of sialic acid between hosts. This dramatic difference in the number of sialylated glycans between hosts was confirmed by analysis of PNGase F-released glycans using MALDI-ToF MS. These differences in glycosylation, however, did not greatly translate into differences in antibody recognition. Biosensor assays showed that gp145 produced in CHO-K1 had similar affinity toward the broadly neutralizing antibodies, 2G12 and PG16, as the gp145 produced in Expi293F. Additionally, both immunogens showed the same reactivity against plasma of HIV-infected patients. Taken together, these results support the notion that there are sizeable differences in the glycosylation of Env depending on the expression host. How these differences translate to vaccine efficacy remains unknown.

Antioxidant enzyme dysfunction in monocytes and CSF of Hispanic women with HIV-associated cognitive impairment.

HIV-associated cognitive neurological disorders (HAND) prevail in the antiretroviral therapy era. Proteomics analysis of CSF revealed expression of Cu/Zn superoxide dismutase (Cu/Zn SOD) in Hispanic women with cognitive impairment (CI). We tested the hypothesis that there is reduced capacity of antioxidant enzymes in CI by measures of expression and activity of Cu/Zn SOD, catalase, and Se-glutathione peroxidase in HAND. Our results showed that the function of these antioxidants was decreased in the CSF and monocytes of women with CI. These findings have important implications regarding their possible contribution to oxidative stress and in the diagnosis and therapy for HAND.

Release of Soluble Insulin Receptor From Neurons by Cerebrospinal Fluid From Patients With Neurocognitive Dysfunction and HIV Infection.

Previously, we found that high levels of soluble insulin receptor (sIR) in the cerebrospinal fluid (CSF) of an HIV-infected women cohort were associated with the presence and severity of HIV-associated neurocognitive disorders (HAND). In this study we investigated if CSF from this population, HIV-1 Tat, and selected cytokines induces sIR secretion from human neuronal cells. Twenty-three (23) HIV-seropositive women stratified by cognitive status and five HIV- seronegative women were evaluated. Soluble IR levels were measured in the extracellular medium of neuronal cells (SH-SY5Y) that were exposed (for 24 h) to the CSF of patients. The levels of sIR, HIV-1 Tat, and cytokine levels (IL-2, IL4, IL-6, IFNγ, TNFα, and IL-10) were quantified in the CSF of participants by ELISA and flow cytometry. Neuronal secretion of sIR was measured after exposure (24 h) to HIV-1 Tat (0.5-250 nM), or specific cytokines. The effects of TNFα and HIV-1 Tat on sIR secretion were also evaluated in the presence of R7050 (TNFα antagonist; 10 nM). Neurons exposed to the CSF of HIV-infected women had higher sIR levels according to the severity of neurocognitive impairment of the participant. Increased CSF sIR levels were associated with the presence and severity of HAND and were positively correlated with CSF HIV-1 Tat levels in HIV-infected women with cognitive impairment. CSF levels of IL-2, IFNγ, and TNFα were significantly increased with HAND. However, only TNFα (5 pg/mL) and HIV-1 Tat (100 nM) induced a significant increase in neuronal sIR secretion after 24 h exposure, an effect that was antagonized when each were combined with R7050. Our data suggests that TNFα and HIV-1 Tat from the CSF of HIV-infected women may regulate the secretion of sIR from neuronal cells and that the effect of HIV-1 Tat on sIR secretion may depend on TNFα receptor activation.

CSF proteomic fingerprints for HIV-associated cognitive impairment.

Cognitive impairment remains a major complication of advanced human immunodeficiency virus (HIV) infection despite the widespread use of anti-retroviral therapy. Diagnosis is made by exclusion making biomarkers of great potential use. Thus, we used an integrated proteomics platform to assess cerebrospinal fluid protein profiles from 50 HIV-1 seropositive Hispanic women. Nine of 38 proteins identified were unique in those patients with cognitive impairment (CI). These proteins were linked to cell signaling, structural function, and antioxidant activities. This work highlights, in a preliminary manner, the utility of proteomic profiling for biomarker discovery for HIV-1 associated cognitive dysfunction.

Incidence and clinical characteristics of Guillain-Barré syndrome before the introduction of Zika virus in Puerto Rico.

BACKGROUND: Zika virus has been associated with increases in Guillain-Barré syndrome (GBS) incidence. A GBS incidence estimation and clinical description was performed to assess baseline GBS epidemiology before the introduction of Zika virus in Puerto Rico. METHODS: Hospitalization administrative data from an island-wide insurance claims database and U.S. Census Bureau population estimates provided a crude GBS incidence for 2013. This estimate was adjusted using the proportion of GBS cases meeting Brighton criteria for confirmed GBS from nine reference hospitals. Characteristics of confirmed GBS cases in the same nine hospitals during 2012-2015 are described. RESULTS: A total of 136 GBS hospitalization claims were filed in 2013 (crude GBS incidence was 3.8 per 100,000 population). The adjusted GBS incidence was 1.7 per 100,000 population. Of 67 confirmed GBS cases during 2012-2015, 66% had an antecedent illness. Median time from antecedent illness to GBS onset was 7days. Most cases (67%) occurred during July-September. CONCLUSIONS: Puerto Rico's GBS incidence for 2013 was estimated using a combination of administrative data and medical records review; this method could be employed in other regions to monitor GBS incidence before and after the introduction of GBS infectious triggers.