Publications

CD4(+) T cells differentiate into multiple effector types, but it is unclear how they form memory T cells during infection in vivo. Profiling virus-specific CD4(+) T cells revealed that effector cells with T helper 1 (Th1) or T follicular helper (Tfh) cell characteristics differentiated into memory cells, although expression of Tfh cell markers declined over time. In contrast to virus-specific effector CD8(+) T cells, increased IL-7R expression was not a reliable marker of CD4(+) memory precursor cells. However, decreased Ly6C and T-bet (Tbx21) expression distinguished a subset of Th1 cells that displayed greater longevity and proliferative responses to secondary infection. Moreover, the gene expression profile of Ly6C(lo)T-bet(int) Th1 effector cells was virtually identical to mature memory CD4(+) T cells, indicating early maturation of memory CD4(+) T cell features in this subset during acute viral infection. This study provides a framework for memory CD4(+) T cell development after acute viral infection.

Helicobacter pylori epidemiology in sub-Saharan Africa, particularly among children, has been little investigated. A secondary endpoint of our study was to examine for associations between the seroprevalence of H. pylori and the incidence of malaria. We explored H. pylori prevalence by measuring serum IgG antibodies to H. pylori whole cell and cytotoxin-associated gene A (CagA) antigens by ELISA in a longitudinal cohort of 200 Ugandan children, aged 1-10 years at enrollment, in whom malaria incidence was followed over 572 person-years. First-sample seroprevalence for H. pylori -specific IgG (63%) and for the H. pylori protein CagA (78.5%) were both high, and they were positively associated with advancing age (per each 1-year age increase, OR (95% CI): 1.60 (1.39-1.85), P<0.001). We observed nearly universal prevalence of CagA+ H. pylori by the age of 10 years in Kampala and found no evidence that H. pylori-positivity is protective against malaria.

Cardiac magnetic resonance imaging (CMR) has an important emerging role in the evaluation and management of patients who present with symptoms concerning for acute coronary syndrome (ACS). This paper discusses the role of CMR in the emergency department setting, where CMR can aid in the early and accurate diagnosis of non-ST elevation ACS in low and intermediate risk patients. For those with confirmed myocardial infarction (MI), CMR provides comprehensive prognostic information and can readily diagnose structural complications related to MI. Furthermore, the pattern of late gadolinium enhancement (LGE) seen on CMR can help determine the etiology of cardiac injury in the subset of patients presenting with ACS who do not have obstructive coronary artery disease by angiography.

The orbitofrontal cortex (OFC) and its interactions with the basolateral amygdala (BLA) are critical for goal-directed behavior, especially for adapting to changes in reward value. Here we used a reinforcer devaluation paradigm to investigate the contribution of OFC to this behavior in four macaques. Subjects that had formed associations between objects and two different primary reinforcers (foods) were presented with choices of objects overlying the two different foods. When one of the two foods was devalued by selective satiation, the subjects shifted their choices toward the objects that represented the nonsated food reward (devaluation effect). Transient inactivation of OFC by infusions of the GABA(A) receptor agonist muscimol into area 13 blocked the devaluation effect: the monkeys did not reduce their selection of objects associated with the devalued food. This effect was observed when OFC was inactivated during both satiation and the choice test, and during the choice test only. This supports our hypothesis that OFC activity is required during the postsatiety object choice period to guide the selection of objects. This finding sharply contrasts with the role of BLA in the same devaluation process (Wellman et al., 2005). Whereas activity in BLA was required during the selective satiation procedure, it was not necessary for guiding the subsequent object choice. Our results are the first to demonstrate that transient inactivation of OFC is sufficient to disrupt the devaluation effect, and to document a role for OFC distinct from that of BLA for the conditioned reinforcer devaluation process in monkeys.

In patients with acute decompensated heart failure (ADHF), treatment aimed at adequate decongestion of the volume overloaded state is essential. Despite diuretic therapy, many patients remain volume overloaded and symptomatic. In addition, adverse effects related to diuretic treatment are common, including worsening kidney function and electrolyte disturbances. The development of decreased kidney function during treatment affects the response to diuretic therapy and is associated with important clinical outcomes, including mortality. The occurrence of diuretic resistance and the morbidity and mortality associated with diuretic therapy has stimulated interest to develop effective and safe treatment strategies that maximize decongestion and minimize decreased kidney function. During the last few decades, extracorporeal ultrafiltration has been used to remove fluid from diuretic-refractory hypervolemic patients. Recent clinical studies using user-friendly machines have suggested that ultrafiltration may be highly effective for decongesting patients with ADHF. Many questions remain regarding the comparative impact of diuretics and ultrafiltration on important clinical outcomes and adverse effects, including decreased kidney function. This article serves as a summary of key clinical studies addressing these points. The overall goal is to assist practicing clinicians who are contemplating the use of ultrafiltration for a patient with ADHF.

Primary prevention efforts aimed at sexual risk behaviors are critical. This experiment was designed to investigate the effects of alcohol intoxication and sexual arousal, as well as person variables of alcohol sex expectancies and attitudes toward condom use, on hypothesized determinants of sexual risk behaviors among men who have sex with men (MSM). The participants were 117 MSM aged 21-50 years who were randomly assigned to one of six separate experimental conditions created by the combination of beverage administration (water control, placebo or alcohol designed to raise blood alcohol level to .07%) and sexual arousal (low or high, manipulated by participants' viewing non-erotic or mildly erotic film clips). Participants attended two experimental sessions. The first session included completing questionnaires about beliefs about alcohol's effects on sex and attitudes toward condoms' effect on sexual pleasure. The second session involved the beverage condition and arousal manipulations. Following these, participants viewed and responded to two interactive videos depicting high sexual risk scenarios. Participants also completed the CARE, a measure of risk perceptions. The dependent variables were behavioral skills, intentions to have unsafe sex, and "risk exposure," derived from responses to the videos. The results of both planned and exploratory analyses showed general support for the hypothesized enhancement of alcohol's effects on sexual risk by both sexual arousal and expectancies. Also as predicted, condom attitudes showed direct relationships to risk exposure and intentions. Implications of the findings for models of alcohol's effects on sexual risk and for the development of HIV prevention interventions were discussed.