Correlating neighborhood-level deprivation and pediatric metabolic dysfunction-associated steatotic liver disease.

OBJECTIVES: The primary objective of this study is to further explore associations between social influencers of health and markers of disease severity at the time of presentation of patients with pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) using neighborhood-level Area Deprivation Index (ADI) scores. METHODS: A retrospective cross-sectional study was conducted among 344 pediatric MASLD patients. Each patient received an ADI score based on their 9-digit zip code. Groups were defined as low (≤5) and high (6≥) ADI. Associations between ADI and symptomatology and laboratory values at presentation, as well as initial liver biopsy pathology were tested via analyses of covariance, χ2 testing, and logistic regressions. RESULTS: The mean ADI was 6.54 (standard deviation = 2.09). ADI groups did not significantly differ in age of presentation, type of presentation, or associated conditions, except for the higher ADI group having on average lower vitamin D levels (26.70 vs. 29.91, p = 0.02) and being two times more likely to also be diagnosed with low high-density lipoprotein (HDL) levels (p = 0.04, 95% CI 1.04-3.89). Mean transaminases and histopathologic nonalcoholic fatty liver disease (NAFLD) Activity Scores did not significantly differ between ADI groups. CONCLUSIONS: Pediatric patients with MASLD in this study span the entire spectrum of neighborhood deprivation. There were no differences in presentation characteristics or severity of MASLD, aside from lower HDL-cholesterol and vitamin D values in the high ADI group. Area deprivation was not predictive of more severe disease as assessed by serum transaminases and liver biopsy NAFLD activity scores.

Repetition attenuates the influence of recency on recognition memory: Behavioral and electrophysiological evidence.

Studies of recognition memory often demonstrate a recency effect on behavioral performance, whereby response times (RTs) are faster for stimuli that were previously presented recently as opposed to more remotely in the past. One account of this relationship between performance and presentation lag posits that memories are accessed by serially searching backward in time, such that RT indicates the self-terminating moment of such a process. Here, we investigated the conditions under which this serial search gives way to more efficient means of retrieving memories. Event-related potentials (ERPs) were recorded during a continuous recognition task, in which subjects made binary old/new judgments to stimuli that were each presented up to four times across a range of lags. Stimulus repetition and shorter presentation lag both gave rise to speeded RTs, consistent with previous findings, and we novelly extend these effects to a robust latency measure of the left parietal ERP correlate of retrieval success. Importantly, the relationship between repetition and recency was further elucidated, such that repetition attenuated lag-related differences that were initially present in both the behavioral and neural latency data. These findings are consistent with the idea that an effortful search through recent memory can quickly be abandoned in favor of relying on more efficient "time-independent" cognitive processes or neural signals.

Is Cognitive Impairment Related to Violations of Rationality? A Laboratory Alcohol Intoxication Study Testing Transitivity of Preference.

Alcohol intoxication is well known to impair a number of cognitive abilities required for sound decision making. We tested whether an intoxicating dose of alcohol altered whether individuals satisfied a basic property of rational decision making, transitivity of preference. Our study was within-subjects in design and our analysis teased apart stable, yet error-prone, preferences from variable, error-free preferences. We find that alcohol intoxication does not appear to play a major role in determining whether subjects violate transitivity. For a minority of individuals, we find that alcohol intoxication does impact how they select among and/or perceive lotteries with similar attribute values. This, in turn, can cause them to alter various aspects of their preference structure.

Failure to reactivate salient episodic information during indirect and direct tests of memory retrieval.

Several fMRI and EEG studies have demonstrated that successful episodic retrieval is accompanied by the reactivation of cortical regions that were active during encoding. These findings are consistent with influential models of episodic memory that posit that conscious retrieval (recollection) relies on hippocampally-mediated cortical reinstatement. Evidence of reactivation corresponding to episodic information that is beyond conscious awareness at the time of memory retrieval, however, is limited. A recent exception is from an EEG study by Wimber, Maaß, Staudigl, Richardson-Klavehn, and Hanslmayr et al. (2009) in which words were encoded in the context of highly salient visual flicker entrainment and then presented at retrieval in the absence of any flicker. In that study, coherent (phase-locked) neural activity was observed at the corresponding entrained frequencies during retrieval, consistent with the notion that encoding representations were reactivated. Given the important implications of unconscious reactivation to past findings and the modeling literature, the current study set out to provide a direct replication of the previous study. Additionally, an attempt was made to extend such findings to intentional retrieval by acquiring EEG while subjects were explicitly asked to make memory judgments about the flicker frequency from encoding. Throughout a comprehensive set of analyses, the current study consistently failed to demonstrate evidence for unconscious reactivation, and instead provided support that test items were indistinguishable according to their prior encoding context. The findings thus establish an important boundary condition for the involvement of cortical reinstatement in episodic memory.

Synthetic Receptors Induce Anti Angiogenic and Stress Signaling on Human First Trimester Cytotrophoblast Cells.

The cytotrophoblast (CTB) cells of the human placenta have membrane receptors that bind certain cardiotonic steroids (CTS) found in blood plasma. One of these, marinobufagenin, is a key factor in the etiology of preeclampsia. Herein, we used synthetic receptors (SR) to study their effectiveness on the angiogenic profile of human first trimester CTB cells. The humanextravillous CTB cells (Sw.71) used in this study were derived from first trimester chorionic villus tissue. Culture media of CTB cells treated with ≥1 nM SR level revealed sFlt-1 (Soluble fms-like tyrosine kinase-1) was significantly increased while VEGF (vascular endothelial growth factor) was significantly decreased in the culture media (* p < 0.05 for each) The AT2 receptor (Angiotensin II receptor type 2) expression was significantly upregulated in ≥1 nM SR-treated CTB cells as compared to basal; however, the AT1 (Angiotensin II receptor, type 1) and VEGFR-1 (vascular endothelial growth factor receptor 1) receptor expression was significantly downregulated (* p < 0.05 for each). Our results show that the anti-proliferative and anti-angiogenic effects of SR on CTB cells are similar to the effects of CTS. The observed anti angiogenic activity of SR on CTB cells demonstrates that the functionalized-urea/thiourea molecules may be useful as potent inhibitors to prevent CTS-induced impairment of CTB cells.

Morphometric analysis of gray matter integrity in individuals with early-treated phenylketonuria.

The most widely-reported neurologic finding in individuals with early-treated phenylketonuria (PKU) is abnormality in the white matter of the brain. In contrast, much less is known regarding the impact of PKU on cortical gray matter (GM) structures. Presently, we applied advanced morphometric methods to the analysis of high-resolution structural MRI images from a sample of 19 individuals with early-treated PKU and an age- and gender-matched comparison group of 22 healthy individuals without PKU. Data analysis revealed decreased GM volume in parietal cortex for the PKU group compared with the non-PKU group. A similar trend was observed for occipital GM volume. There was no evidence of group-related differences in frontal or temporal GM volume. Within the PKU group, we also found a significant relationship between blood phenylalanine levels and GM volume for select posterior cortical sub-regions. Taken together with previous research on white matter and gray matter abnormalities in PKU, the present findings point to the posterior cortices as the primary site of neurostructural changes related to early-treated PKU.

Separate and joint effects of alcohol and caffeine on conflict monitoring and adaptation.

RATIONALE: Caffeine is commonly believed to offset the acute effects of alcohol, but some evidence suggests that cognitive processes remain impaired when caffeine and alcohol are coadministered. OBJECTIVES: No previous study has investigated the separate and joint effects of alcohol and caffeine on conflict monitoring and adaptation, processes thought to be critical for self-regulation. This was the purpose of the current study. METHODS: Healthy, young adult social drinkers recruited from the community completed a flanker task after consuming one of four beverages in a 2 × 2 experimental design: Alcohol + caffeine, alcohol + placebo caffeine, placebo alcohol + caffeine, or placebo alcohol + placebo caffeine. Accuracy, response time, and the amplitude of the N2 component of the event-related potential (ERP), a neural index of conflict monitoring, were examined as a function of whether or not conflict was present (i.e., whether or not flankers were compatible with the target) on both the previous trial and the current trial. RESULTS: Alcohol did not abolish conflict monitoring or adaptation. Caffeine eliminated conflict adaptation in sequential trials but also enhanced neural conflict monitoring. The combined effect of alcohol and caffeine was apparent only in how previous conflict affected the neural conflict monitoring response. CONCLUSIONS: Together, the findings suggest that caffeine leads to exaggeration of attentional resource utilization, which could provide short-term benefits but lead to problems conserving resources for when they are most needed.

Episodic retrieval involves early and sustained effects of reactivating information from encoding.

Several fMRI studies have shown a correspondence between the brain regions activated during encoding and retrieval, consistent with the view that memory retrieval involves hippocampally-mediated reinstatement of cortical activity. With the limited temporal resolution of fMRI, the precise timing of such reactivation is unclear, calling into question the functional significance of these effects. Whereas reactivation influencing retrieval should emerge with neural correlates of retrieval success, that signifying post-retrieval monitoring would trail retrieval. The present study employed EEG to provide a temporal landmark of retrieval success from which we could investigate the sub-trial time course of reactivation. Pattern-classification analyses revealed that early-onsetting reactivation differentiated the outcome of recognition-memory judgments and was associated with individual differences in behavioral accuracy, while reactivation was also evident in a sustained form later in the trial. The EEG findings suggest that, whereas prior fMRI findings could be interpreted as reflecting the contribution of reinstatement to retrieval success, they could also indicate the maintenance of episodic information in service of post-retrieval evaluation.