Eye Movements Predict Recollective Experience

Previously encountered stimuli can bring to mind a vivid memory of the episodic context in which the stimulus was first experienced ("remembered'' stimuli), or can simply seem familiar ("known'' stimuli). Past studies suggest that more attentional resources are required to encode stimuli that are subsequently remembered than known. However, it is unclear if the attentional resources are distributed differently during encoding and recognition of remembered and known stimuli. Here, we record eye movements while participants encode photos, and later while indicating whether the photos are remembered, known or new. Eye fixations were more clustered during both encoding and recognition of remembered photos relative to known photos. Thus, recognition of photos that bring to mind a vivid memory for the episodic context in which they were experienced is associated with less distributed overt attention during encoding and recognition. The results suggest that remembering is related to encoding of a few distinct details of a photo rather than the photo as a whole. In turn, during recognition remembering may be trigged by enhanced memory for the salient details of the photos

Alcohol reversibly disrupts TNF-α/TACE interactions in the cell membrane

BACKGROUND: Alcohol abuse has long been known to adversely affect innate and adaptive immune responses and pre-dispose to infections. One cellular mechanism responsible for this effect is alcohol-induced suppression of TNF-α (TNF) by mononuclear phagocytes. We have previously shown that alcohol in part inhibits TNF-α processing by TNF converting enzyme (TACE) in human monocytes. We hypothesized that the chain length of the alcohol is critical for post-transcriptional suppression of TNF secretion. METHODS: Due to the complex transcriptional and post-transcriptional regulation of TNF in macrophages, to specifically study TNF processing at the cell membrane we performed transient transfections of A549 cells with the TNF cDNA driven by the heterologous CMV promoter. TNF/TACE interactions at the cell surface were assessed using fluorescent resonance energy transfer (FRET) microscopy. RESULTS: The single carbon alcohol, methanol suppressed neither TNF secretion nor FRET efficiency between TNF and TACE. However, 2, 3, and 4 carbon alcohols were potent suppressors of TNF processing and FRET efficiency. The effect of ethanol, a 2-carbon alcohol was reversible. CONCLUSION: These data show that inhibition of TNF-α processing by acute ethanol is a direct affect of ethanol on the cell membrane and is reversible upon cessation or metabolism

Novel Use of Surveillance Data to Detect HIV-Infected Persons with Sustained High Viral Load and Durable Virologic Suppression in New York City

Background: Monitoring of the uptake and efficacy of ART in a population often relies on cross-sectional data, providing limited information that could be used to design specific targeted intervention programs. Using repeated measures of viral load (VL) surveillance data, we aimed to estimate and characterize the proportion of persons living with HIV/AIDS (PLWHA) in New York City (NYC) with sustained high VL (SHVL) and durably suppressed VL (DSVL). Methods/Principal Findings: Retrospective cohort study of all persons reported to the NYC HIV Surveillance Registry who were alive and $12 years old by the end of 2005 and who had$2 VL tests in 2006 and 2007. SHVL and DSVL were defined as PLWHA with 2 consecutive VLs $100,000 copies/mL and PLWHA with all VLs #400 copies/mL, respectively. Logistic regression models using generalized estimating equations were used to model the association between SHVL and covariates. There were 56,836 PLWHA, of whom 7 % had SHVL and 38 % had DSVL. Compared to those without SHVL, persons with SHVL were more likely to be younger, black and have injection drug use (IDU) risk. PLWHA with SHVL were more likely to die by 2007 and be younger by nearly ten years, on average. Conclusions/Significance: Nearly 60 % of PLWHA in 2005 had multiple VLs, of whom almost 40 % had DSVL, suggesting successful ART uptake. A small proportion had SHVL, representing groups known to have suboptimal engagement in care. This group should be targeted for additional outreach to reduce morbidity and secondary transmission. Measures based o

Cross-Sectional Analysis of Late HAART Initiation in Latin America and the Caribbean: Late Testers and Late Presenters

Background: Starting HAART in a very advanced stage of disease is assumed to be the most prevalent form of initiation in HIV-infected subjects in developing countries. Data from Latin America and the Caribbean is still lacking. Our main objective was to determine the frequency, risk factors and trends in time for being late HAART initiator (LHI) in this region. Methodology: Cross-sectional analysis from 9817 HIV-infected treatment-naive patients initiating HAART at 6 sites (Argentina, Chile, Haiti, Honduras, Peru and Mexico) from October 1999 to July 2010. LHI had CD4$^+$ count $\leq$200cells/mm$^3$ prior to HAART. Late testers (LT) were those LHI who initiated HAART within 6 months of HIV diagnosis. Late presenters (LP) initiated after 6 months of diagnosis. Prevalence, risk factors and trends over time were analyzed. Principal Findings: Among subjects starting HAART (n = 9817) who had baseline CD4$^+$ available (n = 8515), 76% were LHI: Argentina (56%[95%CI:52–59]), Chile (80%[95%CI:77–82]), Haiti (76%[95%CI:74–77]), Honduras (91%[95%CI:87–94]), Mexico (79%[95%CI:75–83]), Peru (86%[95%CI:84–88]). The proportion of LHI statistically changed over time (except in Honduras) ($p\leq0.02$; Honduras p = 0.7), with a tendency towards lower rates in recent years. Males had increased risk of LHI in Chile, Haiti, Peru, and in the combined site analyses (CSA). Older patients were more likely LHI in Argentina and Peru (OR 1.21 per +10-year of age, 95%CI:1.02–1.45; OR 1.20, 95%CI:1.02–1.43; respectively), but not in CSA (OR 1.07, 95%CI:0.94–1.21). Higher education was associated with decreased risk for LHI in Chile (OR 0.92 per +1-year of education, 95%CI:0.87–0.98) (similar trends in Mexico, Peru, and CSA). LHI with date of HIV-diagnosis available, 55% were LT and 45% LP. Conclusion: LHI was highly prevalent in CCASAnet sites, mostly due to LT; the main risk factors associated were being male and older age. Earlier HIV-diagnosis and earlier treatment initiation are needed to maximize benefits from HAART in the region

Clinical Predictors of Immune Reconstitution following Combination Antiretroviral Therapy in Patients from the Australian HIV Observational Database

A small but significant number of patients do not achieve CD4 T-cell counts >500 cells/µl despite years of suppressive cART. These patients remain at risk of AIDS and non-AIDS defining illnesses. The aim of this study was to identify clinical factors associated with CD4 T-cell recovery following long-term cART.Patients with the following inclusion criteria were selected from the Australian HIV Observational Database (AHOD): cART as their first regimen initiated at CD4 T-cell count <500 cells/µl, HIV RNA<500 copies/ml after 6 months of cART and sustained for at least 12 months. The Cox proportional hazards model was used to identify determinants associated with time to achieve CD4 T-cell counts >500 cells/µl and >200 cells/µl.501 patients were eligible for inclusion from AHOD (n = 2853). The median (IQR) age and baseline CD4 T-cell counts were 39 (32-47) years and 236 (130-350) cells/µl, respectively. A major strength of this study is the long follow-up duration, median (IQR) = 6.5(3-10) years. Most patients (80%) achieved CD4 T-cell counts >500 cells/µl, but in 8%, this took >5 years. Among the patients who failed to reach a CD4 T-cell count >500 cells/µl, 16% received cART for >10 years. In a multivariate analysis, faster time to achieve a CD4 T-cell count >500 cells/µl was associated with higher baseline CD4 T-cell counts (p<0.001), younger age (p = 0.019) and treatment initiation with a protease inhibitor (PI)-based regimen (vs. non-nucleoside reverse transcriptase inhibitor, NNRTI; p = 0.043). Factors associated with achieving CD4 T-cell counts >200 cells/µl included higher baseline CD4 T-cell count (p<0.001), not having a prior AIDS-defining illness (p = 0.018) and higher baseline HIV RNA (p<0.001).The time taken to achieve a CD4 T-cell count >500 cells/µl despite long-term cART is prolonged in a subset of patients in AHOD. Starting cART early with a PI-based regimen (vs. NNRTI-based regimen) is associated with more rapid recovery of a CD4 T-cell count >500 cells/µl

Evolving uses of oral reverse transcriptase inhibitors in the HIV-1 epidemic: From treatment to prevention

The HIV epidemic continues unabated, with no highly effective vaccine and no cure. Each new infection has significant economic, social and human costs and prevention efforts are now as great a priority as global antiretroviral therapy (ART) scale up. Reverse transcriptase inhibitors, the first licensed class of ART, have been at the forefront of treatment and prevention of mother to child transmission over the past two decades. Now, their use in adult prevention is being