CD8+CD28-CD127loCD39+ regulatory T-cell expansion: A new possible pathogenic mechanism for HIV infection?

BACKGROUND: HIV-associated immunodeficiency is related to loss of CD4+ T cells. This mechanism does not explain certain manifestations of HIV disease, such as immunodeficiency events in patients with greater than 500 CD4+ T cells/µL. CD8+CD28-CD127loCD39+ T cells are regulatory T (Treg) lymphocytes that are highly concentrated within the tumor microenvironment and never analyzed in the circulation of HIV-infected patients. OBJECTIVES: We sought to analyze the frequency of CD8+CD28-CD127loCD39+ Treg cells in the circulation of HIV-infected patients. METHODS: The frequency of circulating CD8+CD28-CD127loCD39+ Treg cells was analyzed and correlated with viral load and CD4+ T-cell counts/percentages in 93 HIV-1-infected patients subdivided as follows: naive (n = 63), elite controllers (n = 19), long-term nonprogressors (n = 7), and HIV-infected patients affected by tumor (n = 4). The same analyses were performed in HIV-negative patients with cancer (n = 53), hepatitis C virus-infected patients (n = 17), and healthy donors (n = 173). RESULTS: HIV-infected patients had increased circulating levels of functional CD8+CD28-CD127loCD39+ Treg cells. These cells showed antigen specificity against HIV proteins. Their frequency after antiretroviral therapy (ART) correlated with HIV viremia, CD4+ T-cell counts, and immune activation markers, suggesting their pathogenic involvement in AIDS- or non-AIDS-related complications. Their increase after initiation of ART heralded a lack of virologic or clinical response, and hence their monitoring is clinically relevant. CONCLUSION: HIV infection induces remarkable expansion of CD8+CD28-CD127loCD39+ Treg cells, the frequency of which correlates with both clinical disease and signs of chronic immune cell activation. Monitoring their frequency in the circulation is a new marker of response to ART when effects on viremia and clinical response are not met.

Moving mirrors: a high-density EEG study investigating the effect of camera movements on motor cortex activation during action observation.

Action execution-perception links (mirror mechanism) have been repeatedly suggested to play crucial roles in social cognition. Remarkably, the designs of most studies exploring this topic so far excluded even the simplest traces of social interaction, such as a movement of the observer toward another individual. This study introduces a new design by investigating the effects of camera movements, possibly simulating the observer's own approaching movement toward the scene. We conducted a combined high-density EEG and behavioral study investigating motor cortex activation during action observation measured by event-related desynchronization and resynchronization (ERD/ERS) of the mu rhythm. Stimuli were videos showing a goal-related hand action filmed while using the camera in four different ways: filming from a fixed position, zooming in on the scene, approaching the scene by means of a dolly, and approaching the scene by means of a steadycam. Results demonstrated a consistently stronger ERD of the mu rhythm for videos that were filmed while approaching the scene with a steadycam. Furthermore, videos in which the zoom was applied reliably demonstrated a stronger rebound. A rating task showed that videos in which the camera approached the scene were felt as more involving and the steadycam was most able to produce a visual experience close to the one of a human approaching the scene. These results suggest that filming technique predicts time course specifics of ERD/ERS during action observation with only videos simulating the natural vision of a walking human observer eliciting a stronger ERD than videos filmed from a fixed position. This demonstrates the utility of ecologically designed studies for exploring social cognition.

Genotypic determination of HIV tropism in a cohort of patients perinatally infected with HIV-1 and exposed to antiretroviral therapy.

The aim of this study was to determine the coreceptor tropism by performing genotypic HIV-1 tropism testing in a cohort of patients perinatally infected with HIV-1 and exposed to antiretroviral therapy. Genotypic coreceptor tropism was determined in patients with HIV-1 RNA<100 copies/mL using PBMC samples by gp120 V3 sequencing followed by geno2pheno interpretation (set at a false positive rate [FPR] of 20%) and in patients with ≯100 copies/mL using plasma samples (set at a FPR of 20%), according to European guidelines. Out of 55 patients, 50 had an HIV-1 subtype B strain, and mean (SD) age was 18.2 (4.6) years. The median duration of antiretroviral therapy was 13 years (range, 3-23). Thirty-three (60%) patients harbored the R5 virus. At the time of the testing, the median CD4+ T lymphocyte cell count and percentage were 705 cells/mm3 (474-905) and 32.5% in group R5 and 626 cells/mm3 (450-755) and 31.7% in group X4/D-M, respectively. The nadir of CD4+ T-cell count in groups R5 and X4/D-M were 322 cells/mm3 (230-427) and 340 cells/mm3 (242-356), respectively. These differences were not statistically significant. Fifteen patients had HIV-1 RNA ≯50 copies/mL. The median HIV-1 RNA and HIV-1 DNA were comparable in both groups without a statistical difference. The study provides an overview of the prevalence of coreceptor tropism in a cohort of patients who were vertically infected with HIV-1. The high prevalence of X4/D-M-tropic strains may simply reflect the long-term exposure to HIV.

Use of Soft Cervical Collar among Whiplash Patients in Two Italian Emergency Departments Is Associated with Persistence of Symptoms: A Propensity Score Matching Analysis.

PURPOSE: Although the use of soft cervical collars in the emergency department (ED), for whiplash-associated disorders (WAD), is controversial, it is still widely adopted. The purpose of our study was to investigate the impact of the early use of soft cervical collars on the return to the ED, within three months of a road traffic collision. METHODS: We conducted a retrospective observational study on WAD patients from two EDs in Verona (Italy). Patients in the earlier acute phase of WAD (within 48 h from the trauma) were included; those with serious conditions (WAD IV) were excluded. As an end point, we considered patients who returned to the ED complaining of WAD symptoms within three months as positive outcome for WAD persistence. RESULTS: 2162 patients were included; of those, 85.4% (n = 1847/2162) received a soft cervical collar prescription. Further, 8.4% (n = 156/1847) of those with a soft cervical collar prescription, and 2.5% (n = 8/315) of those without a soft cervical collar (p < 0.001) returned to the ED within three months. The use of the soft cervical collar was an independent risk factor for ED return within three months, with an OR, adjusted for possible clinical confounders, equal to 3.418 (95% CI 1.653-7.069; p < 0.001). After the propensity score matching, 25.5% of the patients (n = 25/98) using the soft cervical collar returned to the ED at three months, compared to the 6.1% (n = 6/98) that did not adopt the soft cervical collar. The use of a soft cervical collar was associated with ED return with an OR = 4.314 (95% CI 2.066-11.668; p = 0.001). CONCLUSIONS: Our study shows that the positioning of the soft collar in a cohort of patients with acute WAD, following a rear-end car collision, is an independent potential risk factor to the return to the ED. Clinically, the use of the collar is a non-recommended practice and seems to be related to an increased risk of delayed recovery. There is a need to inform healthcare providers involved in the ED of the aim to limit the use of the soft cervical collar. A closer collaboration between clinicians (e.g., physicians, physical therapists, nurses) is suggested in the ED. Future primary studies should determine differences between having used or not having used the collar, and compare early physical therapy in the ED compared with the utilization of the collar.

Embodying the camera: An EEG study on the effect of camera movements on film spectators´ sensorimotor cortex activation.

One key feature of film consists in its power to bodily engage the viewer. Previous research has suggested lens and camera movements to be among the most effective stylistic devices involved in such engagement. In an EEG experiment we assessed the role of such movements in modulating specific spectators´ neural and experiential responses, likely reflecting such engagement. We produced short video clips of an empty room with a still, a zooming and a moving camera (steadicam) that might simulate the movement of an observer in different ways. We found an event related desynchronization of the beta components of the rolandic mu rhythm that was stronger for the clips produced with steadicam than for those produced with a still or zooming camera. No equivalent modulation in the attention related occipital areas was found, thus confirming the sensorimotor nature of spectators´ neural responses to the film clips. The present study provides the first empirical evidence that filmic means such as camera movements alone can modulate spectators' bodily engagement with film.

Active for life: final results from the translation of two physical activity programs.

BACKGROUND: Most evidence-based programs are never translated into community settings and thus never make a public health impact. DESIGN: Active for Life (AFL) was a 4-year translational initiative using a pre-post, quasi-experimental design. Data were collected from 2003 to 2007. Analyses were conducted in 2005 and 2008. SETTING/PARTICIPANTS: Nine lead organizations at 12 sites participated. Active Choices participants (n=2503) averaged 65.8 years (80% women, 41% non-Hispanic white). Active Living Every Day (ALED) participants (n=3388) averaged 70.6 years (83% women, 64% non-Hispanic white). INTERVENTION: In AFL, Active Choices was a 6-month telephone-based and ALED a 20-week group-based lifestyle behavior change program designed to increase physical activity, and both were grounded in social cognitive theory and the transtheoretical model. The interventions were evaluated in Years 1, 3, and 4. An adapted shortened ALED program was evaluated in Year 4. MAIN OUTCOME MEASURE: Moderate- to vigorous-intensity physical activity, assessed with the CHAMPS self-reported measure. RESULTS: Posttest survey response rates were 61% for Active Choices and 70% for ALED. Significant increases in moderate- to vigorous-intensity physical activity, total physical activity, and satisfaction with body appearance and function, and decreases in BMI were seen for both programs. Depressive symptoms and perceived stress, both low at pretest, also decreased over time in ALED. Results were generally consistent across years and sites. CONCLUSIONS: Active Choices and ALED were successfully translated across a range of real-world settings. Study samples were substantially larger, more ethnically and economically diverse, and more representative of older adult's health conditions than in efficacy studies, yet the magnitude of effect sizes were comparable.

"Cuts in Action": A High-Density EEG Study Investigating the Neural Correlates of Different Editing Techniques in Film.

In spite of their striking differences with real-life perception, films are perceived and understood without effort. Cognitive film theory attributes this to the system of continuity editing, a system of editing guidelines outlining the effect of different cuts and edits on spectators. A major principle in this framework is the 180° rule, a rule recommendation that, to avoid spectators' attention to the editing, two edited shots of the same event or action should not be filmed from angles differing in a way that expectations of spatial continuity are strongly violated. In the present study, we used high-density EEG to explore the neural underpinnings of this rule. In particular, our analysis shows that cuts and edits in general elicit early ERP component indicating the registration of syntactic violations as known from language, music, and action processing. However, continuity edits and cuts-across the line differ from each other regarding later components likely to be indicating the differences in spatial remapping as well as in the degree of conscious awareness of one's own perception. Interestingly, a time-frequency analysis of the occipital alpha rhythm did not support the hypothesis that such differences in processing routes are mainly linked to visual attention. On the contrary, our study found specific modulations of the central mu rhythm ERD as an indicator of sensorimotor activity, suggesting that sensorimotor networks might play an important role. We think that these findings shed new light on current discussions about the role of attention and embodied perception in film perception and should be considered when explaining spectators' different experience of different kinds of cuts.

[Added value of SPECT/CT over planar imaging in improving sentinel node detection in breast cancer patients]. / Il valore aggiunto della SPECT/CT rispetto all'imaging planare nel migliorare la ricerca del linfonodo sentinella in pazienti con carcinoma mammario.

UNLABELLED: The aim of the study was to assess the diagnostic contribution of hybrid SPECT/CT lymphoscintigraphy compared to planar imaging for the correct identification of sentinel lymph nodes (SLN) in breast cancer (BC) patients. MATERIALS AND METHODS: 73 planar and SPECT/CT lymphoscintigraphies were performed in 70 consecutive patients with BC (70 women, mean age 55.7±12.0 years, range 26-84) for pre-surgical SLNs research. Cohen'K was performed to evaluate the agreement between both techniques; their diagnostic capability was evaluated by the Student's t-test for paired data. RESULTS: In 54/73 (73.9%) lymphoscintigraphies, SLNs were detected both on planar and SPECT/CT images. In 19/73 (26.1%) discordant cases, planar technique showed a higher number of SLNs in 4/19 lymphoscintigraphies, while SPECT/CT in 15/19. Radio-guided surgery confirmed SPECT/CT findings. Concordance between the two techniques was poor (K=-0.095). Overall, SPECT/CT detected 13 SLNs more than planar imaging (p=0.07). Furthermore, in 17/73 (23.2%) lymphoscintigraphies, SPECT/CT defined the exact SLNs anatomical localization, equivocal on planar images. CONCLUSIONS: SPECT/CT demonstrated added value over planar imaging, providing more information for the best surgical approach. It is useful especially in patients with negative or doubt planar imaging.

Switch from unboosted protease inhibitor to a single-tablet regimen containing rilpivirine improves cholesterol and triglycerides.

This study aimed to evaluate the efficacy, tolerability and potential savings of combined antiretroviral therapy (cART) simplification from an unboosted protease inhibitor (PI) regimen with atazanavir or fosamprenavir to a single-tablet regimen (STR) based on rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) among HIV-1-infected patients with HIV-1 RNA <50 copies/mL. This was a retrospective, multicentre, open-label, 12-week trial. Plasma HIV-1-RNA levels, CD4+ cell counts, cholesterol, triglycerides, bilirubin, glycaemia, creatinine and physical examination were performed at baseline and at scheduled follow-up. All patient costs were calculated and were estimated for 52 weeks of therapy. Fifty-one patients were enrolled [28 male (54.9%)]. At baseline, 30 patients (58.8%) were treated with FTC/TDF, 20 (39.2%) with abacavir/lamivudine and 1 (2.0%) with lamivudine/zidovudine. Thirty-three patients (64.7%) received atazanavir. All patients maintained HIV-RNA <50 copies/mL; the median CD4+ cell count remained stable. Mean triglycerides decreased from 124 mg/dL (range, 39-625) at enrolment to 108.7 mg/dL (range, 39-561) at study end (P = 0.25). At baseline, mean cholesterol was 172.8 ± 38.1 mg/dL and decreased to 161.9 ± 38.6 mg/dL (P = 0.038); likewise, median total bilirubin decreased from 1.07 mg/dL (range, 0.2-4.7) to 0.6 mg/dL (range, 0.13-3.1) (P <0.001). cART-related annual cost reduction with a STR was €3155.47 per patient (-24%). Non-cART patient management expenses were €402.68 vs. €299.10 for atazanavir or fosamprenavir and STR regimens, respectively. Switching to RPV/FTC/TDF from an unboosted PI in virologically suppressed HIV-infected patients is safe and is associated with a reduction in triglycerides, cholesterol and cART-related costs.

Relationship between innate immunity, soluble markers and metabolic-clinical parameters in HIV+ patients ART treated with HIV-RNA<50 cp/mL.

INTRODUCTION: The persistence of immune activation and inflammation in HIV patients with HIV-RNA (VL) undetectable causes many co-morbidities [1-3]. The aim of this study is to correlate monocytes (m) and NK cell activation levels, soluble markers and oxidative stress with clinical, biochemical and metabolic data in HIV-1 infected patients with VL≤50 copies (cp)/mL on antiretroviral therapy. MATERIALS AND METHODS: Multicentre, cross-sectional study in patients with VL≤50 cp/mL and on antiretroviral therapy by at least six months. We studied: activation/homing markers (CD38, HLA-DR, CCR-2, PDL-1) on inflammatory, intermediate, proinflammatory m; activatory receptors NKp30, NKp46 and HLA-DR on NK cells; soluble inflammatory (sCD14, adiponectina, MCP-1) and stress oxidative markers (dRoms, antiRoms). Univariate analyses are performed with non-parametric and Pearson tests. The significant correlations were adjusted for possible known confounding factors (smoking, Cytomegalovirus IgG serology, Raltegravir, Protease Inhibitor [PI] therapy and HCV-RNA) with multivariate analysis. RESULTS: In the 68 patients the positive correlation between age and antiRoms was significant also after adjustment for PI use (p=0.05). The% CD8+T was associated with% proinflammatory m (p=0.043) and with their expression of CCR2 mean fluorescence intensity (MFI) (p=0.012). The% NKp46+ was positively correlated with CD4+T count (p=0.001). The fibrinogen was positively associated with dRoms (p=0.052) and the positive correlation between triglycerides and antiRoms has been confirmed (p<0.001); the impact of antiRoms on HDL/triglycerides ratio (p=0.006) was observed after adjustment for PI use. The BMI was associated with smoking (p=0.011). Only the maraviroc-treated patients showed minimal arterial pressure, fibrinogen and antiRoms lower (p=0.001, 0.004 e 0.006) and sCD14 values higher (p=0.029). CONCLUSIONS: Patients with long history of HIV infection and stable immunological and virological status showed interactions between acquired and innate immunity activation; moreover, the levels of some metabolic and inflammatory parameters correlate with oxidative stress values and innate immunity activation. The age, BMI and smoking impact metabolic and immunological parameters. The correlations between antiretroviral drugs and clinical-immunological parameters need further confirmations.

The ligurian human immunodeficiency virus clinical network: a web tool to manage patients with human immunodeficiency virus in primary care and multicenter clinical trials.

BACKGROUND: In recent years, Highly-Active Anti-Retroviral Therapies (HAARTs) have modified the Human Immunodeficiency Virus (HIV) life-cycle and the disease is now considered chronic. Consequently, a longitudinal and complex follow-up is now required for HIV positive patients during their lifetime. Moreover, patients often encounter various complications due to comorbidities, related to the immunodeficiency state and HAARTs' side effects. Thus, HIV positive patients are involved in multicenter clinical trials (MCTs) to improve treatments and discover a preventive vaccine. Therefore, physicians require proper instruments to access comprehensive patient data for managing patients during follow-ups, and tools for data collection and analysis in MCTs. OBJECTIVE: The Ligurian HIV Clinical Network aims to provide physicians with a Web-tool to administrate HIV positive patients' data within primary-care and to reuse the collected clinical information to perform MCTs in Northern Italy. METHODS: The key aspect of the system is a relational database which allows the storage of various types of clinical information (eg, related to HIV, cardiovascular, or hepatic diseases) in multiple formats. The modular design of the database permits a rapid insertion of new parameters without requiring any changes in the database structure. Furthermore, codes from biomedical ontologies controlled vocabularies ("Logical Observation Identifier Names and Codes", and "International Classification of Diseases 9") and ontologies ("Systematized Nomenclature of Medicine Clinical Terms"), units and normality ranges used by all partners participating in the project were collected to achieve a complete semantic interoperability. Accordingly, data can be automatically normalized through the z score formula and physicians can extract and correctly compare information with external statistical tools. Moreover, to respect patients' privacy and legal issues, a local identifier, determined through an HASH cryptography algorithm, is assigned to each patient during the registration process. The database is managed by a user-friendly Web-platform which allows quick access to information during medical examinations and the reusing of the collected data for present and future MCTs. Furthermore, a bidirectional middleware was created in order to import/export information through HL7 messaging. Hence, data can be manually entered by physicians or automatically collected within HL7-compliant Hospital Information systems. RESULTS: Presently, the direct storage of patients' information from the San Paolo Hospital (Savona, Italy), and San Martino and Galliera hospitals in Genoa is in a test phase. Currently, 8 centers of Infectious Diseases (located in Liguria and Piedmont) are participating in the project and almost 400 HIV positive patients have been recorded in the system. Patient data has been used for primary care and research purposes. Currently, there are 4 on-going MCTs and preliminary results have already been presented at International HIV congresses. CONCLUSIONS: The Web-platform allows effective management, sharing and reuse of information within primary care and clinical research. In the future it is planned to share the clinical information from this network with other HL7-compliant workgroups and to extend the platform to other infective diseases (eg, hepatitis).

Adopting an Evidence-Based Lifestyle Physical Activity Program: Dissemination Study Design and Methods.

BACKGROUND: There is a scarcity of research studies that have examined academic-commercial partnerships to disseminate evidence-based physical activity programs. Understanding this approach to dissemination is essential because academic-commercial partnerships are increasingly common. Private companies have used dissemination channels and strategies to a degree that academicians have not, and declining resources require academicians to explore these partnerships. PURPOSE: This paper describes a retrospective case-control study design including the methods, demographics, organizational decision-making, implementation rates, and marketing strategy for Active Living Every Day (ALED), an evidence-based lifestyle physical activity program that has been commercially available since 2001. Evidence-based public health promotion programs rely on organizations and targeted sectors to disseminate these programs although relatively little is known about organizational-level and sector-level influences that lead to their adoption and implementation. METHODS: Cases (n=154) were eligible if they had signed an ALED license agreement with Human Kinetics (HK), publisher of the program's textbooks and facilitator manuals, between 2001 and 2008. Two types of controls were matched (2:2:1) and stratified by sector and region. Active controls (Control 1; n=319) were organizations that contacted HK to consider adopting ALED. Passive controls (Control 2; n=328) were organizations that received unsolicited marketing materials and did not initiate contact with HK. We used Diffusion of Innovations Theory (DIT) constructs as the basis for developing the survey of cases and controls. RESULTS: Using the multi-method strategy recommended by Dillman, a total of n=801 cases and controls were surveyed. Most organizations were from the fitness sector followed by medical, nongovernmental, governmental, educational, worksite and other sectors with significantly higher response rates from government, educational and medical sectors compared with fitness and other sectors, (p=0.02). More cases reported being involved in the decision to adopt ALED (p<0.0001). Data indicate that a low percentage of controls had ever heard of ALED despite repeated marketing and offering other types of physical activity programs and services. Finally, slightly over half of the adopters reported they had actually implemented the ALED program. CONCLUSION: Dissemination research requires new perspectives and designs to produce valid insights about the results of dissemination efforts. This study design, survey methods and theoretically-based questions can serve as a useful model for other evidence-based public health interventions that are marketed by commercial publishers to better understand key issues related to adoption and implementation of evidence-based programs.