Paradoxically, however, people with high endogenous levels of oxytocin also tend to report relational distress and interpersonal difficulties in their everyday lives. To address these contradictory findings, oxytocin reactivity was measured in response to a well-defined laboratory task in young adult women following recent interpersonal harms. Elevated mean peripheral oxytocin reactivity (but not baseline levels of oxytocin or cortisol reactivity) was associated with increased post-conflict anxiety and decreased levels of forgiveness. These results

corroborate previous research implicating oxytocin as a neuroendocrine marker of relational distress, but not general stress, and demonstrate the utility of studying oxytocin in response Flavopiridol manufacturer to naturally MK-8776 solubility dmso occurring relational events. (C) 2010 Elsevier Ltd. All rights reserved.”
“Nesfatin-1 is a neuropeptide localized in hypothalamic paraventricular nucleus (PVN). Previously, we have reported the mechanism of feeding suppression by nesfatin-1, and also reported the ability of nesfatin-1 in regulating stress response and the circadian feeding pattern.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide also related to

the stress response, feeding, and regulation of cardiovascular and autonomic nervous systems. The neurons with receptors for PACAP are distributed in PVN. However, there are no reports showing the direct effect of PACAP on nesfatin-1 neurons. In order to explore the direct effect of PACAP on PVN nesfatin-1 neuron, we have measured the cytosolic free calcium ([Ca2+](i)) using fura-2 microfluorometry in single neurons Selleckchem LY3023414 isolated from PVN of adult rats, followed by immunocytochemical identification of nesfatin-1 neurons. PACAP at 10(-15) M to 10(-9) M increased [Ca2+](i) in dose dependent manner. PAC1 and VPAC2 receptor agonists also increased [Ca2+](i). Sixteen out of 40 neurons (40%) in PVN responded to 10(-9) M PACAP, and 12 out of 16 neurons (75%) which responded to 10(-9) M PACAP were found to be nesfatin-1 neurons.

In this paper we show that PACAP directly activates nesfatin-1 neurons in PVN. The data suggest that nesfatin-1 controls feeding, stress response or autonomic response under PACAP regulation. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Background: Progesterone, a steroid hormone, has been implicated in many CNS functions including reward, cognition, and neuroprotection. The goal of this study was to examine the dose-dependent effects of progesterone on cognitive performance, smoking urges, and smoking behavior in smokers.

Methods: Thirty female and thirty-four male smokers participated in a double-blind, placebo-controlled study. Female smokers were in the early follicular phase of their menstrual cycle during study participation.

In two experiments, false feedback given about cognitive performance influenced participants’ beliefs about whether they had been allocated to the active treatment or placebo. These beliefs also appeared to influence actual cognitive performance in that participants who believed they had taken the active treatment had higher accuracy in Experiment 1 and faster reaction times in Experiment 2 than those who believed they had been given a placebo. The addition of no treatment control groups in Experiment 2 showed that these effects could not be accounted for by

the feedback manipulation itself, thereby supporting expectancy as a causal factor.

These results indicate the importance of assessing participants’ beliefs about their treatment allocation in real double-blind RCTs and considering if and how these may have affected the trial’s outcome.”
“Genetic variants eFT-508 in vivo of the serotonergic neurotransmitter Evofosfamide system are potential contributing

factors in the pathological processes underlying Alzheimer’s disease (AD). We examined polymorphisms of the serotonin transporter (SLC6A4) and serotonin receptor 2A (HTR2A) genes for possible association with AD, and therefore genotyped 5-HTTLPR, STin2-VNTR and HTR2A T102C polymorphisms in 252 Hungarian AD patients and 234 ethnically matched control individuals. We did not detect statistically significant differences in genotype distribution comparing the AD and the control group when the polymorphisms were investigated separately. Logistic regression analyses, however, revealed an interaction effect between 5-HTTLPR and HTR2A T102C (p = 0.019), but not between 5-HTTLPR and STin2-VNTR (p = 0.494) or STin2-VNTR and HTR2A T102C (p selleck chemicals llc = 0.310) polymorphisms. Our study suggests no individual influence of the investigated polymorphisms but a

potential combined effect of the 5-HTTLPR L/L and HTR2A T102C C/C genotypes on AD risk. However, the results need to be treated with considerable caution, and further analyses in larger samples are required. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Infection of the chestnut blight fungus Cryphonectria parasitica with Cryphonectria hypovirus 1 (CHV1) causes disruption of virulence, pigmentation, and sporulation. Transcriptional downregulation of key developmentally regulated fungal genes occurs during infection, but vegetative growth is unaffected. Previous studies showed that CHV1 utilizes trans-Golgi network (TGN) secretory vesicles for replication. In this study, the fungal cell surface hydrophobin cryparin was chosen as a marker to follow secretion in virally infected and noninfected strains. Subcellular fractionation, cryparin-green fluorescent protein (GFP) fusion, and Western blot studies confirmed that vesicles containing cryparin copurify with the same fractions previously shown to contain elements of the viral replication complex and the TGN resident endoprotease Kex2.

Roberts, Isolation of an internal clock, J. Exp. Psychol. Anim. B 7 (1981) 242-268] with two durations (10s and 40s), and then lesioned the STN by microinjection of ibotenic acid. Lesioned animals were able to maintain precise temporal control, yet were unable to inhibit operant responses late in the trial, at times that were unlikely to yield reinforcement. These results indicate the SHP099 nmr involvement of the STN in impulsive or perseverative response inhibition, but not in temporal processing. (c) 2008 Elsevier Ireland

Ltd. All rights reserved.”
“Although the human transmission of avian H5N1 virus remains low, the prevalence of this highly pathogenic infection in avian species underscores the need for a preventive vaccine that can be made without eggs. Here, we systematically analyze various forms of recombinant hemagglutinin (HA) protein for their potential efficacy as vaccines. Monomeric, trimeric, and oligomeric H5N1 RA proteins were expressed and purified from either insect or mammalian cells. The immunogenicity of different recombinant HA proteins was evaluated by measuring the neutralizing

antibody response. Neutralizing antibodies to H5N1 HA were readily generated in mice immunized with the recombinant HA proteins, but they varied in potency depending on their multimeric nature and cell Lazertinib manufacturer source. Among the HA proteins, a high-molecular-weight oligomer elicited the strongest antibody response, followed by the trimer; the monomer showed minimal efficacy. The coexpression of another viral surface protein, neuraminidase, did not affect the immunogenicity of the HA oligomer, as expected from the immunogenicity of trimers produced from insect cells. As anticipated,

HA expressed in mammalian cells without NA retained the terminal sialic acid residues and failed to bind alpha 2,3-linked sialic acid receptors. Taken together, these results suggest that recombinant HA proteins as individual or oligomeric trimers can elicit potent neutralizing antibody responses to avian H5N1 influenza viruses.”
“Amitriptyline is used to treat neuropathic pain in humans. It produces antinociception in several animal models of pain, and this effect is blocked by methylxanthine adenosine receptor antagonists which implicates adenosine it its actions. Here, the antinociceptive effect 17-DMAG (Alvespimycin) HCl of amitriptyline, and the ability of caffeine to reverse it, were examined using the formalin test (a model of persistent pain) in wild type mice and mice lacking the adenosine A, receptor (All R). Amitriptyline produced dose-related suppression of flinching in wild type mice following both systemic and intraplantar drug administration; both of these effects were unaltered in AIR -/- mice. Following systemic administration, caffeine reversed the systemic effect of amitriptyline in wild type, but not A1R-/- mice; -/+ mice exhibited an intermediate effect.

Here we show

that all low molecular weight proteins of PSII already accumulate in the etioplast membrane fraction in darkness, whereas PsaI and PsaJ of photosystem I (PSI) represent the only low molecular weight proteins that do not accumulate in darkness. We found by BN-PAGE separation of Selleckchem MK-0518 membrane protein complexes and selective MS that the accumulation of one-helix proteins from PSII is light independent and occurs in etioplasts. In contrast, in chloroplasts isolated from light-grown plants, low molecular weight proteins were found to specifically accumulate in PSI and II complexes. Our results demonstrate how plants grown in darkness prepare for the induction of chlorophyll dependent photosystem assembly upon light perception. We anticipate that our investigation will provide the essential means for the analysis of protein assembly in any membrane utilizing low molecular weight protein subunits.”
“Though flow cytometry provides the entire distribution of cellular fluorescence (i.e., “”fluorescence profile”"), only mean fluorescence data are usually considered in studies of ligand-receptor binding. In this study,

we presented a method of the treatment of the temporal evolution of the whole fluorescence profile with a comprehensive statistical approach extended to the reversible binding case. The method was demonstrated in the study of the 1D3 IgM monoclonal antibodies binding to Fc gamma RIIIb receptors (CD16b) on neutrophils. Kinetic experiments were carried out using a FACSCalibur (Becton Dickinson, USA) flow cytometer. For each of four donors, we find more obtained learn more the distribution of the number of Fc gamma RIIIb surface receptors

for neutrophils and the rate constants per receptor: the association rate constant of (2.7 +/- 0.4) x 10(7) M(-1) min(-1), and the dissociation rate constant of (1.3 +/- 0.4) x 10(-1) min(-1). Based on the obtained values, the size of the receptor reaction site was estimated at approximately 1 nm. It was found, that cell receptors distributions differed sufficiently between donors in mean and the skewness values, whereas the coefficient of variation (i.e., the ratio of the standard deviation to the mean) did not vary significantly. (C) 2011 Elsevier. Ltd. All rights reserved.”
“Nuclear factor-kappa B (NF-kappa B) is a transcription factor involved in a wide variety of phenomena including inflammation, immune responses, and cell survival. Abnormal activation of NF-kappa B occurs in many pathological conditions, such as allergic and auto-inflammatory diseases and malignancies. As a result, the signal-induced NF-kappa B activation pathway has been extensively studied and revealed to be regulated by ubiquitination. Several types of polyubiquitin chains exist and the type of chain seems to impact how ubiquitinated proteins are regulated. Recently, different types of polyubiquitin chains, including linear (M1) and K11 chains, have been implicated in NF-kappa B activation.

The stochasticity of p53 regulation, introduced at the levels of gene expression, DNA damage and repair, leads to high heterogeneity of cell responses and causes cell population split after irradiation into subpopulations of apoptotic and surviving cells, with fraction of apoptotic cells growing with the irradiation dose. (C) 2008 Elsevier Ltd. All rights reserved.”
“Nitric oxide production in the colon has been linked to inflammatory https://www.selleckchem.com/products/tucidinostat-chidamide.html bowel disease (IBD) and increased risk for colon

cancer. However, measurements of NO concentration in the inflamed colon have not been available and it is not known what NO levels are pathophysiological. A computational model, based on anatomical length scales and rates of NO production measured in cell cultures, was used to predict spatially varying NO concentrations within a colonic crypt under inflammatory conditions. A variety of scenarios were considered, including different spatial distributions of macrophages and a range of possible macrophage and epithelial synthesis rates for NO. Activated macrophages arranged as a monolayer at the base of the crypt elicited Selleckchem Lapatinib maximum NO concentrations of approximately 0.3 mu M. The epithelial contribution to NO synthesis was calculated to be

negligible. Assuming a uniform macrophage layer, NO synthesis rates greater than 20 mu M/s, or more than three times that measured in vitro, would be necessary to achieve maximum NO concentrations of 1 mu M in the crypt, Thus, unless NO synthesis rates in macrophages and/or epithelial cells greatly exceed those measured in cell cultures, NO concentrations will remain submicromolar in the crypt during inflammation. Additionally, the results were used to predict the range of NO concentrations (< 0.3 mu M) and cumulative NO dose (560 mu M min) experienced by a

given epithelial cell migrating from the base to the top of the crypt. These estimates of NO concentrations in inflamed crypts should facilitate efforts to elucidate the molecular biological linkage between NO exposure and carcinogenesis in IBD. (c) 2008 Elsevier Inc. All rights reserved.”
“The malate-aspartate (M-A) shuttle provides an important mechanism to regulate glycolysis and lactate metabolism in the Selleck KU-60019 heart by transferring reducing equivalents from cytosol into mitochondria. However, experimental characterization of the M-A shuttle has been incomplete because of limitations in quantifying cytosolic and mitochondrial metabolites. In this study, we developed a multicompartment model of cardiac metabolism with detailed presentation of the M-A shuttle to quantitatively predict non-observable fluxes and metabolite concentrations under normal and ischemic conditions in vivo. Model simulations predicted that the M-A shuttle is functionally localized to a subdomain that spans the mitochondrial and cytosolic spaces.

Neuropsychopharmacology (2012) 37, 2456-2466; doi:10.1038/npp.2012.104; published online 27 June 2012″
“Nicotine has been reported to produce both anxiolytic and/or anxiogenic effects in humans and animals.

This study examined whether pretreatment with nicotine would alter anxiety in a unique runway model of approach-avoidance conflict.

Food-restricted rats were trained to run a straight alley once a

day to obtain food upon goal-box entry. Beginning on trial 11, food reward was followed by a series of five foot shocks (0.3-0.4 mA, 0.5 s) in the goal box. Non-shocked control rats continued to run for food only. The resulting association of the goal box with both a positive (food) and negative (foot shock) Defactinib stimulus produced an approach-avoidance conflict (subjects exhibited “”retreat behaviors”" in which they would approach the goal box, stop, and then retreat back towards the start box). Once retreats were established, their sensitivity to nicotine pretreatment (0.0, 0.03, 0.045,

0.06, or 0.075 mg/kg, i.v.) was compared to saline. In subsequent tests, the effects of nicotine (0.06 or 0.03 mg/kg) were examined on spontaneous activity (locomotion) and center-square entries in an open field (anxiety).

Doses of 0.06 and 0.075 mg/kg, but not lower doses of nicotine, reduced the number of runway retreats, selleck kinase inhibitor and 0.06 mg/kg nicotine increased the number of open-field center entries relative to saline. No effects on locomotion were observed.

Nicotine reduced approach-avoidance conflict and increased the rats’ willingness to enter the center of an open field, suggesting that the drug can produce anxiolytic properties and that such

effects may serve as an important factor in the persistence of smoking behavior.”
“Meq is the major Marek’s disease virus (MDV)-encoded oncoprotein and is essential for T-cell lymphomagenesis. Meq and several noncoding RNAs, including three microRNA (MiR) clusters, are expressed from the repeats of the MDV genome during latent infection of T cells. To investigate the state of the chromatin in this and flanking regions, we carried out chromatin immunoprecipitation (ChIP) analysis of covalent histone modifications and associated bound proteins. T-cell lines selleck chemicals and a lymphoma were compared. The chromatin around the promoters for Meq and the noncoding RNAs in both cell lines and the lymphoma were associated with H3K9 acetylation and H3K4 trimethylation, which are marks of transcriptionally active chromatin. These correlated with bound Meq-c-Jun heterodimers. The only binding site for Meq homodimers is located at the lytic origin of replication (OriLyt), next to the lytic gene pp38. This region lacked active marks and was associated with repressive histone modifications (H3K27 and H3K9 trimethylation). DNA CpG methylation was investigated using methylated DNA precipitation (MeDP).

However, the precise mechanisms of prediction are still poorly understood. Forward models, which draw upon the language production system to set up expectations during

comprehension, provide a promising approach in this regard. Here, we present an event-related potential (ERP) study on German Sign Language (DGS) which tested the hypotheses of a forward model perspective VEGFR inhibitor on prediction. Sign languages involve relatively long transition phases between one sign and the next, which should be anticipated as part of a forward model-based prediction even though they are semantically empty. Native speakers of DGS watched videos of naturally signed DGS sentences which either ended with an expected or a (semantically) unexpected sign. Unexpected signs engendered a biphasic N400 late positivity pattern. Crucially, N400 onset

preceded critical sign onset and was thus clearly elicited by properties of the transition phase. The comprehension system thereby clearly anticipated modality-specific information about the realization of the predicted semantic item. These results provide strong converging support for the application of forward models in language comprehension. (C) 2013 Elsevier Ltd. All rights reserved.”
“Objective: We report 30-day and 12-month results of endovascular treatment with the Valiant Thoracic Stent Graft System (Medtronic Vascular, Santa Rosa, Calif) in patients with descending thoracic aortic aneurysms of degenerative etiology. The Valiant stent graft is an evolution of the Talent thoracic

GSK1838705A ic50 stent graft (Medtronic Vascular).

Methods: The VALOR II (Evaluation of the Clinical Performance of the Valiant Thoracic Stent Graft System in the Treatment of Descending Thoracic Aneurysms of Degenerative Etiology in Subjects Who Are Candidates for Endovascular Repair) was a prospective, nonrandomized, pivotal trial conducted at 24 U. S. sites with enrollment between December 2006 and September 2009. Standard follow-up examinations, including physical examination, computed tomography, and chest radiography, were at 1, 6, and 12 months, and annually through 5 years. VALOR II outcomes were compared with those from the pivotal VALOR (Evaluation of the Medtronic Vascular Talent Thoracic Stent Graft System for the Treatment of Thoracic Aortic Aneurysms) see more trial of the Talent stent graft, which enrolled 195 patients with similar enrollment criteria.

Results: VALOR II enrolled 160 patients. Compared with VALOR patients, VALOR II patients had similar age and sex distribution but higher rates of cardiovascular risk factors and significantly more severe modified Society for Vascular Surgery/American Association for Vascular Surgery risk scores. Stent graft delivery and deployment were successful in 154 patients (96.3%). Outcomes at 30 days in VALOR II were perioperative mortality, 3.

ADNF-9 administration significantly prevented alcohol-induced reductions in fetal brain weight. In addition, ADNF-9 prevented an alcohol-induced selleck increase in cell death in the primordium of the cerebral cortex and ganglionic eminence. Western blot analysis of the mitochondria, protein fractions revealed that ADNF-9 administration prevented an alcohol-induced reduction in the BcI2 level. Moreover, an analysis of the proteins in the upstream signaling pathway revealed that ADNF-9 downregulated the phosphorylation of JNK. These data indicate that the mitochondrial BcI2 pathway

and JNK upstream signaling pathway are the intracellular targets of ADNF-9. The neuroprotective mechanism of action of ADNF-9 provides a direction for potential therapeutics against alcohol-induced neural damage involving mitochondrial dysfunction. Published by Elsevier 8-Bromo-cAMP clinical trial Ltd on behalf of IBRO.”
“Objectives: A protective inferior vena cava (IVC) filter may later be incorporated into a chronic postthrombotic ilio-caval obstruction (occlusive, requiring recanalization, or nonocclusive).

This study aims to assess the safety and stent-related outcome following stenting across an obstructed filter.

Methods: From 1997 to 2009, 708 limbs had stenting for postthrombotic ilio-caval outflow obstruction (occlusion in 121 limbs). In 25 patients, an IVC filter was obstructed (Group X). The site was crossed by a guidewire and

balloon dilated. The filter was markedly displaced sidewise or remodeled. A stent was placed across the IVC filter and redilated. AZD5153 solubility dmso In 28 other patients, the cephalad stenting terminated below a patent IVC filter (Group B). The remaining 655 patients had no previous IVC filter placement (Group no IVC filter present [NF]). The patients were followed to assess potency. The types of reintervention were noted.

Results: The stenting maneuver through a variety of previously inserted IVC filters was safely performed without an apparent tear of the IVC, no clinical bleeding or abdominal symptoms, or pulmonary embolism. Mortality was nil; morbidity minimal. The primary and secondary cumulative potency rates at 54 months for limbs with postthrombotic obstruction were with and without IVC filter (38% and 40%; P = .1701 and 79% and 86%; P = .1947, respectively), and for limbs with stenting across the filter (Group X) and stent termination below the filter (Group B; 32% and 42%; P = .3064 and 75% and 84%; P = .2788, respectively), not statistically different. When Group X alone was compared with Group NF, the secondary potency rate was, however, significantly lower (75% vs 86%; P = .0453), suggesting that crossing of the stent was associated with reduced potency. Occlusive postthrombotic disease requiring recanalization was more frequent in Group X than in Group B and Group NF (68%, 25%, and 15%, respectively; P = .004).

The human cell repopulation at the site of injection and the other bones were serially investigated. Interestingly, CD34(+)CD38(+), CD34(+)CD38(-), and CD34(-) SRCs began to migrate to other bones 2 and 5 weeks after the transplantation, respectively. Accordingly, the initiation of migration seemed to differ between the CD34(+) and CD34(-) SRCs. In addition, CD34(+)CD38(+) SB202190 cell line SRCs only sustained a short-term repopulation. However, both CD34(+)CD38(-)

and CD34(-) SRCs had longer-term repopulation capacity. Taken together, these findings showed that CD34(-) SRCs show different in vivo kinetics, thus suggesting that the identified CD34(-) SRCs are a distinct class of primitive HSCs in comparison to the CD34(+)CD38(-) and CD34(+)CD38(-) SRCs. Leukemia (2010) 24, 162-168; doi:10.1038/leu.2009.206; published online 1 October 2009″
“Mesenchymal learn more stromal cells are promising candidate donor cells for promoting functional tissue repair following traumatic spinal cord injury (SCI), however, the mechanism(s) of action remain

poorly defined. Here, we describe an in vitro study of the axon growth-promoting properties of highly enriched populations of adult human mesenchymal stromal cells (hMSC). A random, non-oriented pattern of neuritic outgrowth was observed from dissociated adult rat DRG neurons seeded onto confluent A431 cells and PLL/laminin positive control substrata. Confluent hMSC formed arrays of similarly orientated cell bodies and

processes which supported the regeneration of significantly more primary neurites but a slightly lower overall neuritic length than was observed during over the PLL/laminin control substrate. The hMSC exerted a strong influence on the direction of neuritic outgrowth, with many regenerating processes following the orientation of underlying hMSC. The production of extracellular matrix appeared to be responsible for neuritic directionality, but the release of growth factors was a significant promoter for DRG neuritic outgrowth. This suggests that further investigations into the properties of hMSC may be of particular interest in the development of transplant-mediated strategies intending to promote functional axonal regeneration after SCI. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“The pathogenesis of infant acute lymphoblastic leukemia (ALL) is still not well defined. Short latency to leukemia and very high concordance rate for ALL in Mixed-Lineage Leukemia (MLL)-positive infant twins suggest that the MLL rearrangement itself could be sufficient for overt leukemia. Attempts to generate a suitable mouse model for MLL-AF4-positive ALL did not thoroughly resolve the issue of whether cooperating mutations are required to reduce latency and to generate overt leukemia in vivo.

One

patient needed retransplantation. At a median of 40 months post-transplant, 13 of 16 patients (81%) in this Tubastatin A mw high-risk cohort were alive and cured from their underlying disease.

Interpretation Monoclonal antibody-based conditioning seems well tolerated and can achieve curative engraftment even in patients with severe organ toxicity or DNA repair defects, or both. This novel approach represents a shift from the paradigm that intensive chemotherapy or radiotherapy, or both, is needed for donor stem-cell engraftment. This antibody-based conditioning regimen may reduce toxicity and late effects and enable SCT in virtually any primary immunodeficiency patient with a matched donor.”
“Aging impacts memory formation and the engagement of frontal and medial temporal regions. However, much of the research to date has focused on the encoding of neutral verbal and visual information. The present fMRI study investigated age differences in a social encoding task while participants made judgments about the self or another person.

Although previous studies identified an intact self-reference effect with age, subserved by robust engagement of medial prefrontal cortex (mPFC) by both young and older adults, we identified a number of age differences. BI-D1870 mouse In regions including superior mPFC, inferior prefrontal cortex, and anterior and posterior cingulate cortex, young and older adults exhibited reversals in the pattern of activity for self and other conditions. Whereas young primarily evidenced subsequent forgetting effects in the self-reference condition, older adults demonstrated subsequent memory effects in the other-reference condition. These results indicate fundamental differences across the age groups in the engagement of elaborative encoding processes. We suggest that

older adults may encode information about the self in a more normative manner, whereas young adults focus on encoding the unique aspects of the self and distinguishing the self from others. (C) 2009 Elsevier Ltd. All rights this website reserved.”
“One of the greatest challenges facing post-apartheid South Africa is the control of the concomitant HIV and tuberculosis epidemics. HIV continues to spread relentlessly, and tuberculosis has been declared a national emergency. In 2007, South Africa, with 0.7% of the world’s population, had 17% of the global burden of HIV infection, and one of the world’s worst tuberculosis epidemics, compounded by rising drug resistance and HIV co-infection. Until recently, the South African Government’s response to these diseases has been marked by denial, lack of political will, and poor implementation of policies and programmes. Nonetheless, there have been notable achievements in disease management, including substantial improvements in access to condoms, expansion of tuberculosis control efforts, and scale-up of free antiretroviral therapy (ART).