Objective Power spectral analysis of heart rate variability is used clinically to assess cardiac autonomic function. High frequency power is related to respiratory sinus arrhythmia and therefore to parasympathetic cardiovagal tone. The relationship of low frequency (LF) power to cardiac sympathetic tone is less clear. We reported previously that LF power may reflect baroreflex function; however, in the previous study LF power was not adjusted for possible influences of respiration. In this study we assessed relationships of LF power, including respiration-adjusted LF power (LFa) using the ANSAR ANX 3.0 device, with cardiac sympathetic innervation and baroreflex function in chronic autonomic failure patients who either had or did not have neuroimaging evidence of cardiac sympathetic denervation. Methods Values for LF power with patients seated at baseline and during the Valsalva maneuver were compared between groups with low or normal myocardial concentrations of 6-[18F]fluorodopamine-derived radioactivity. Baroreflex-cardiovagal gain (BRS) was calculated from the slope of cardiac interbeat interval vs. systolic pressure during the Valsalva maneuver with subjects supine. Results Individual values for LF and LFa were unrelated to myocardial 6-[18F]fluorodopamine-derived radioactivity. During both sitting rest and the Valsalva maneuver the logs of LF and LFa correlated positively with the log of BRS (r=0.61, p=0.0005; r=0.47, p=0.009; r=0.69, p<0.0001; r=0.60, p=0.0006). Patients with low BRS (≤3 msec/mm Hg) had low LF and LFa regardless of the status of cardiac innervation. Conclusion LF and LFa reflect baroreflex function independently of cardiac sympathetic innervation.

Objective. To examine the relationship between changes in anti-double-stranded DNA (anti-dsDNA) antibody levels and the risk of renal flare in patients with systemic lupus erythematosus (SLE), using data from 2 randomized, controlled trials.Methods. Analyses were based on 487 patients with SLE and a history of lupus nephritis who had an anti-dsDNA antibody titer >15 IU/ml at baseline, as measured by Farr assay. Results are presented for the combined population of patients, the placebo arms, and the drug treatment arms in which a dsDNA-based bioconjugate (abetimus sodium; LJP 394) was used.Results. Changes in anti-dsDNA antibody levels were inversely correlated with changes in the C3 level (P < 0.0001 in both trials). Cox proportional hazards regression models showed that changes in anti-dsDNA antibody levels correlated with the risk of renal flare. The models predicted that a point estimate of a 50% reduction in anti-dsDNA antibody levels is associated with a 52% reduction (95% confidence interval [95% CI] 26-68%, nominal P ‫؍‬ 0.0007) and a 53% reduction (95% CI 33-69%, nominal P < 0.0001) in the risk of renal flare in the 2 trials, respectively. In the 2 trials, the incidence of renal flare was lower in patients with sustained reductions in anti-dsDNA antibodies (3.0% and 4.1%, respectively) than in patients with stable or increasing antibody levels (21.3% and 20.3%, respectively).Conclusion. Changes in anti-dsDNA antibody levels were directly correlated with the risk of renal flare and inversely correlated with changes in the C3 level. Reducing anti-dsDNA antibody levels may represent a therapeutic objective in SLE patients with lupus nephritis, because it is associated with a reduced risk of renal flare.Anti-double-stranded DNA (anti-dsDNA) antibodies are diagnostic for systemic lupus erythematosus (SLE) (1) and have been implicated in the underlying pathogenesis of SLE renal disease and other disease manifestations (2-7). Immune complexes containing anti-

Baclofen has been suggested as a potential pharmacotherapy for alcohol use disorder, but the clinical data are conflicting. Here we investigated the biobehavioral effects of baclofen in a sample of anxious alcohol-dependent individuals. This was a randomized, double-blind, placebo-controlled, human laboratory study in non-treatment seeking alcohol-dependent individuals with high trait anxiety (N=34). Participants received baclofen (30 mg per day) or placebo for at least 8 days, then performed an experimental session consisting of alcohol cue-reactivity followed by alcohol administration procedure (alcohol priming, then alcohol self-administration). Total amount of alcohol self-administered was the primary outcome; alcohol craving, subjective/physiological responses and mood/anxiety symptoms were also evaluated. There was no significant medication effect on the total amount of alcohol consumed during the alcohol self-administration (P=0.76). Baclofen blunted the positive association between maximum breath alcohol concentration during priming and the amount of alcohol consumption (significant interaction, P=0.03). Ratings of feeling intoxicated were significantly higher in the baclofen group after consuming the priming drink (P=0.006). During the self-administration session, baclofen significantly increased ratings of feeling high (P=0.01) and intoxicated (P=0.01). A significant reduction in heart rate (P<0.001) and a trend-level increase in diastolic blood pressure (P=0.06) were also detected in the baclofen group during the alcohol laboratory session. In conclusion, baclofen was shown to affect subjective and physiological responses to alcohol drinking in anxious alcohol-dependent individuals. These results do not support an anti-craving or anti-reinforcing effect of baclofen, but rather suggest that baclofen may act as a substitution medication for alcohol use disorder.

A stage critical in mammalian development is embryo implantation. At this point, the blastocyst establishes a close interaction with the uterine tissues, a step necessary for its continued embryonic development. In many mammalian species, including man, uterine expression of the cytokine, leukemia inhibitory factor (LIF) is coincident with the onset of implantation and in mice LIF is essential to this process. The reasons for implantation failure have not been established. Here we show in LIF-deficient mice that up to the onset of implantation, changes in uterine cell proliferation, hormone levels, blastocyst localization, as well as expression of lactoferrin and Muc-1, do not differ from wild-types. However, the uterus fails to respond to the presence of embryos or to artificial stimuli by decidualizing. In mice, implantation and decidualization are induced by nidatory estrogen. We show that uterine expression of LIF is up-regulated by estrogen and LIF can replace nidatory estrogen at inducing both implantation and decidualization in ovariectomized mice. Implantation of LIF-deficient embryos in the LIF-deficient females, with normal development to term is rescued by i.p. injection of LIF. Transient expression of LIF on D4 of pregnancy is therefore only required to induce a state of receptivity in the uterus permitting embryo implantation and decidualization. LIF is neither required by the embryo for development nor for the maintenance of pregnancy.