Antigen-independent induction of Tim-3 expression on human T cells by the common γ-chain cytokines IL-2, IL-7, IL-15, and IL-21 is associated with proliferation and is dependent on the phosphoinositide 3-kinase pathway.

T cell Ig mucin domain-containing molecule 3 (Tim-3) is a glycoprotein found on the surface of a subset of CD8(+) and Th1 CD4(+) T cells. Elevated expression of Tim-3 on virus-specific T cells during chronic viral infections, such as HIV-1, hepatitis B virus, and hepatitis C virus, positively correlates with viral load. Tim-3(+) cytotoxic T cells are dysfunctional and are unable to secrete effector cytokines, such as IFN-γ and TNF-α.

Safety assessment and immunogenicity of a cell-culture-derived influenza vaccine in adults and elderly subjects over three successive influenza seasons.

Background: Adult and elderly subjects previously immunized with cell culture-derived (CCIV; Optaflu(®)) or egg-derived (TIV; Agrippal(®)) trivalent influenza vaccines were enrolled in two extension studies (E1 and E2) to evaluate safety and immunogenicity after revaccination with CCIV/TIV alone or in combination with concomitant pneumococcal vaccine (PV).

Methods: Adults and elderly subjects (n = 2609) were randomized 1:1 in E1 and allocated 3:1 in E2 to receive CCIV/TIV. In E2, a subset of elderly subjects was randomized to receive CCIV/TIV, with or without PV.

Temporal trends and determinants of longitudinal change in 25-hydroxyvitamin D and parathyroid hormone levels.

Vitamin D is essential for facilitating calcium absorption and preventing increases in parathyroid hormone (PTH), which can augment bone resorption. Our objectives were to examine serum levels of 25-hydroxyvitamin D [25(OH)D] and PTH, and factors related to longitudinal change in a population-based cohort. This is the first longitudinal population-based study looking at PTH and 25(OH)D levels.

Aliphatic alcohols of illegally produced spirits can act synergistically on superoxide-anion production by human granulocytes.

Context: Aliphatic alcohols present in illegally produced spirits in a large number of low and middle income countries have been implicated in the etiology of chronic liver disease and cirrhosis. Previous studies have confirmed that chronic alcoholism can lead to increased susceptibility to infectious diseases. Reduced superoxide-anion (O(2)·(-)) production by granulocytes could provide a mechanism by which antimicrobial defense is impaired in alcoholics.

Mucosal correlates of isolated HIV semen shedding during effective antiretroviral therapy.

Effective antiretroviral therapy (ART) suppresses the blood HIV RNA viral load (VL) below the level of detection. However, some individuals intermittently shed HIV RNA in semen despite suppression of viremia, a phenomenon termed "isolated HIV semen shedding (IHS)". In a previously reported clinical study, we collected blood and semen samples from HIV-infected men for 6 months after ART initiation, and documented IHS at ≥1 visit in almost half of the participants, independent of ART regimen or semen drug levels.

A case of a potential drug interaction between clobazam and etravirine-based antiretroviral therapy.

The cytochrome P450 isoforms primarily involved in clobazam metabolism are CYP3A4 and 2C19. Drugs that modulate these enzymes would then be expected to alter the exposure of clobazam and its major metabolites. Etravirine, a second-generation non-nucleoside reverse transcriptase inhibitor has been shown to induce CYP3A4, while inhibiting CYP2C9 and CYP2C19.

Immunologic effectiveness of maraviroc- and raltegravir-containing regimens (R+M+) versus raltegravir-based regimens that do not include maraviroc (R+M-).

Objective: To compare the immunologic effectiveness of raltegravir-maraviroc (R+M+)-based regimens with raltegravir-based regimens that do not include maraviroc (R+M-) in treatment-experienced patients in clinical practice.

Methods: We conducted a retrospective study of treatment-experienced HIV-infected adults receiving either R+M+- or R+M--based therapy. Longitudinal CD4 counts were analyzed using a linear mixed model.

Is intake of vitamin D and calcium important for cardiovascular health in elderly obese patients?

There is compelling evidence that bariatric weight loss reduces cardiovascular complications; however, these still tend to be the most common cause of late death after surgical intervention. In a prospective cohort study, correlations of dietary nutrients with indexes of vascular health were sought, with emphasis on vitamin D and calcium. Clinically stable obese outpatient subjects (>60 years old, N = 44) were interviewed about dietary macro and micronutrients.

Circulating endothelial progenitor cell levels are not reduced in HIV-infected men.

Reduced levels of endothelial progenitor cells (EPCs) have been associated with increased cardiovascular (CV) risk, but limited data are available on EPC levels in the human immunodeficiency virus (HIV)-infected population. EPCs (CD45(dim)/CD34(+)/kinase domain receptor(+)) from 36 HIV-uninfected and 30 antiretroviral therapy-naive HIV-infected men without known CV risk factors were enumerated using flow cytometry. The mean EPC levels (± standard error of the mean) were 1.

Recognizing cognitive and psychiatric changes in the post-highly active antiretroviral therapy era.

Amid numerous complications that plague the health and quality of life of people living with HIV, neurocognitive and psychiatric illnesses pose unique challenges. While there remains uncertainty with respect to the pathophysiology surrounding these disorders, their adverse implications are increasingly recognized. Left undetected, they have the potential to significantly impact patient well being, adherence to antiretroviral treatment and overall health outcomes.

Human endogenous retrovirus K(HML-2) Gag- and Env-specific T-cell responses are infrequently detected in HIV-1-infected subjects using standard peptide matrix-based screening.

T-cell responses to human endogenous retrovirus (HERV) K(HML-2) Gag and Env were mapped in HIV-1-infected subjects using 15 mer peptides. Small peptide pools and high concentrations were used to maximize sensitivity. In the 23 subjects studied, only three bona fide HERV-K(HML-2)-specific responses were detected.

Four-year follow-up of polyalkylimide gel use for the treatment of HIV-associated lipoatrophy.

Purpose: To evaluate polyalkylamide gel (PAIG) use in treating HIV-associated facial lipoatrophy (FLA) 4 years after its injection in an open-label, randomized controlled trial (RCT).

Methods: Five patients were treated with PAIG in a pilot study, and 31 patients were subsequently enrolled in the RCT of immediate or delayed (12 weeks later) PAIG injections. Endpoints included proportion of participants with complications; changes in FLA severity score (FLSS); and quality of life (QoL), depression, anxiety, and satisfaction scores.

Loss of the signaling adaptor TRAF1 causes CD8+ T cell dysregulation during human and murine chronic infection.

The signaling adaptor TNFR-associated factor 1 (TRAF1) is specifically lost from virus-specific CD8 T cells during the chronic phase of infection with HIV in humans or lymphocytic choriomeningitis virus (LCMV) clone 13 in mice. In contrast, TRAF1 is maintained at higher levels in virus-specific T cells of HIV controllers or after acute LCMV infection. TRAF1 expression negatively correlates with programmed death 1 expression and HIV load and knockdown of TRAF1 in CD8 T cells from viral controllers results in decreased HIV suppression ex vivo.

Beyond fear appeals: contradicting positive smoking outcome expectancies to influence smokers' implicit attitudes, perception, and behavior.

Smokers often have (implicit or explicit) positive smoking outcome expectancies that motivate them to smoke. For instance, they may feel that smoking is relaxing, that it improves concentration, or that it is seen as cool and attractive by peers. These expectations are, for the most part, illusory.

Calcium and bone metabolism disorders during pregnancy and lactation.

Pregnancy and lactation cause a substantial increase in demand for calcium that is met by different maternal adaptations within each period. Intestinal calcium absorption more than doubles during pregnancy, whereas the maternal skeleton resorbs to provide most of the calcium content of breast milk during lactation. These maternal adaptations also affect the presentation, diagnosis, and management of disorders of calcium and bone metabolism.

Endometrial epithelial cell response to semen from HIV-infected men during different stages of infection is distinct and can drive HIV-1-long terminal repeat.

Objectives: Although more than 60% of HIV transmission occurs via semen, little is known about the immune impact of seminal plasma on HIV susceptibility. Here, we examined the level of selected immunomodulatory factors in seminal plasma from HIV-uninfected and therapy-naive, HIV-infected men in acute and chronic stages; the cytokine response elicited by seminal plasma in genital epithelial cells (GECs); and whether any GEC response to seminal plasma could drive HIV replication in infected T cells.

Methods: A panel of nine cytokines and chemokines was measured in seminal plasma from HIV-uninfected and HIV-infected men and in primary GEC cultures following seminal plasma exposure.

Effect of raltegravir intensification on HIV proviral DNA in the blood and gut mucosa of men on long-term therapy: a randomized controlled trial.

Background: Highly active antiretroviral therapy (HAART) dramatically reduces plasma HIV-1 viremia. However, despite completely suppressive HAART, it has been suggested that low-levels of viral replication may persist in the gut mucosa and elsewhere in individuals on long-term HAART.

Objective: We conducted a double-blind randomized, placebo-controlled trial evaluating whether intensification of HAART in long-term virologically suppressed individuals with raltegravir is associated with a reduction in the level of proviral HIV-1 DNA in CD4(+) T cells in blood and the sigmoid colon (gut).

Predicting fracture using 2D finite element modelling.

A decrease in bone density at the hip or spine has been shown to increase the risk of fracture. A limitation of the bone mineral density (BMD) measurement is that it provides only a measure of a bone sample's average density when projected onto a 2D surface. Effectively, what determines bone fracture is whether an applied load exceeds ultimate strength, with both bone tissue material properties (can be approximated through bone density), and geometry playing a role.

Bone development in the fetus and neonate: role of the calciotropic hormones.

During embryonic and fetal development much of the skeleton initiates as a cartilaginous scaffold, which is progressively resorbed and replaced by bone. Endochondral bone formation continues until the growth plates fuse during puberty. At all life stages adequate delivery of mineral is required for the skeleton to achieve and maintain appropriate mineral content and strength.

Impact of collection method on assessment of semen HIV RNA viral load.

Background: The blood HIV RNA viral load is the best-defined predictor of HIV transmission, in part due to ease of measurement and the correlation of blood and genital tract (semen or cervico-vaginal) viral load, although recent studies found semen HIV RNA concentration to be a stronger predictor of HIV transmission. There is currently no standardized method for semen collection when measuring HIV RNA concentration. Therefore, we compared two collection techniques in order to study of the impact of antiretroviral therapy on the semen viral load.

Spine-hip T-score difference predicts major osteoporotic fracture risk independent of FRAX(®): a population-based report from CAMOS.

The WHO fracture risk assessment tool (FRAX(®)) estimates an individual's 10-yr major osteoporotic and hip fracture probabilities. When bone mineral density (BMD) is included in the FRAX calculation, only the femoral neck measurement can be used. Recently, a procedure was reported for adjusting major osteoporotic fracture probability from FRAX with femoral neck BMD based on the difference (offset) between the lumbar spine and the femoral neck T-score values.

T cell Activation does not drive CD4 decline in longitudinally followed HIV-infected Elite Controllers.

Background: Elite controllers (EC) are a rare subset of HIV infected individuals who control viral load below 50 copies/ml of plasma without treatment.

Methods: Thirty four EC were studied. The slope of CD4 count change was available for 25 of these subjects.

Relationship between residual plasma viremia and the size of HIV proviral DNA reservoirs in infected individuals receiving effective antiretroviral therapy.

Residual plasma viremia (<50 copies/mL) persists in certain human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART); however, the relationship between the degree of residual plasma viremia, the size of HIV reservoirs, and the level of immune activation has not been delineated. Here, we demonstrate that residual plasma viremia correlates with the size of the CD4(+) T cell viral reservoir, but not with markers of immune activation, suggesting that reactivation of the latent viral reservoir may not be the sole source of residual plasma viremia. Novel therapeutic strategies aimed at targeting the source of residual viremia may be necessary to achieve viral eradication.