Clinical analysis of etiology, risk factors and outcome in patients with acute kidney injury.

Acute kidney injury is characterized by a rapid loss of renal excretory function with the increase of nitrogen compounds in the blood and with different outcome. Objective: Since descriptions of the risk factors and sequelae of acute kidney injury (AKI) remain relatively limited, the objective of this study was to determine etiology and clinical characteristics of AKI, as well as risk factors for adverse outcome of renal function and death in AKI patients. Methods: We retrospectively studied a cohort of 84 adult AKI patients admitted to Nephrology Clinic in University Clinical Centre Sarajevo during period 2012-2014. Demographic, laboratory and clinical parameters were retrieved. The in-hospital and 6 months mortality were recorded. Renal function outcome was defined 3 months following discharge. Results: Majority of patients were older (median age 73.5 years) with great severity of AKI (Stage III in 78.5% of cases) and high burden of comorbidities (mean Charlson comorbidity index, CCI score 6.4±3.05). The most common causes of AKI were acute interstitial nephritis (16.7%), heart failure (15.5%), gastroenterocolitis (13.1%), and sepsis (12%). Renal function recovery was recorded in 48.8% of patients, with prevalence of 10.7% of intrahospital mortality and 37.3% of 6 months mortality. Risk factors for poor outcome of renal function and mortality in AKI patients were increasing age and higher CCI score, while protective factor was higher diuresis. Sepsis proved to be risk factor for deat

A preliminary study of the human brain response to oral sucrose and its association with recent drinking

BACKGROUND: A preference for sweet tastes has been repeatedly shown to be associated with alcohol preference in both animals and humans. In this study, we tested the extent to which recent drinking is related to blood oxygen level-dependent (BOLD) activation from an intensely sweet solution in orbitofrontal areas known to respond to primary rewards. METHODS: Sixteen right-handed, non-treatment-seeking, healthy volunteers (mean age: 26 years; 75% male) were recruited from the community. All underwent a taste test using a range of sucrose concentrations, as well as functional magnetic resonance imaging (fMRI) during pseudorandom, event-driven stimulation with water and a 0.83 M concentration of sucrose in water. RESULTS: [Sucrose > water] provoked a significant BOLD activation in primary gustatory cortex and amygdala, as well as in the right ventral striatum and in bilateral orbitofrontal cortex. Drinks/drinking day correlated significantly with the activation as extracted from the left orbital area (r = 0.52, p = 0.04 after correcting for a bilateral comparison). Using stepwise multiple regression, the addition of rated sucrose liking accounted for significantly more variance in drinks/drinking day than did left orbital activation alone (multiple R = 0.79, p = 0.002). CONCLUSIONS: Both the orbitofrontal response to an intensely sweet taste and rated liking of that taste accounted for significant variance in drinking behavior. The brain response to sweet tastes may be an important phenotype of alcoholism risk

An fMRI Study of Responses to Sexual Stimuli as a Function of Gender and Sensation Seeking: A Preliminary Analysis

Although sexual cues produce stronger neural activation in men than in women, mechanisms underlying this differential response are unclear. We examined the relationship of sensation seeking and the brain’s response to sexual stimuli across gender in 27 subjects (14 men, M = 25.2 years, SD = 3.6, 85.2% Caucasian) who underwent functional magnetic resonance imaging (fMRI) while viewing sexual and nonsexual images. Whole-brain corrected significant clusters of regional activation were extracted and associated with gender, sensation seeking, and sexual behaviors. Men responded more to sexual than nonsexual images in the anterior cingulate/medial prefrontal cortex (ACC/mPFC), anterior insula/lateral orbitofrontal cortex, bilateral amygdala, and occipital regions. Sensation seeking related positively to ACC/mPFC (r = 0.65, p = 0.01) and left amygdala (r = 0.66, p = 0.01) response in men alone, with both of these correlations being significantly larger in men than in women (ps < 0.03). The relationship between brain responses and self-reported high-risk and low-risk sexual behaviors showed interesting, albeit nonsignificant, gender-specific trends. These findings suggest the relationship between sexual responsivity, sensation seeking, and sexual behavior is gender specific. This study indicates a need to identify the gender-specific mechanisms that underlie sexual responsivity and behaviors. In addition, it demonstrates that the nature of stimuli used to induce positive mood in imaging and other studies should be carefully considered

Aberrations of anterior insular cortex functional connectivity in nontreatment-seeking alcoholics

An emergent literature suggests that resting state functional magnetic resonance imaging (rsfMRI) functional connectivity (FC) patterns are aberrant in alcohol use disorder (AUD) populations. The salience network (SAL) is an established set of brain regions prominent in salience attribution and valuation, and includes the anterior insular cortex (AIC). The SAL is thought to play a role in AUD through directing increased attention to interoceptive cues of intoxication. There is very little information on the salience network (SAL) in AUD, and, in particular, there are no data on SAL FC in currently drinking, nontreatment seeking individuals with AUD (NTS). rsfMRI data from 16 NTS and 21 social drinkers (SD) were compared using FC correlation maps from ten seed regions of interest in the bilateral AIC. As anticipated, SD subjects demonstrated greater insular FC with frontal and parietal regions. We also found that, compared to SD, NTS had higher insular FC with hippocampal and medial orbitofrontal regions. The apparent overactivity in brain networks involved in salience, learning, and behavioral control in NTS suggests possible mechanisms in the development and maintenance of AUD

Pairing Neutral Cues with Alcohol Intoxication: New Findings in Executive and Attention Networks

Rationale: Alcohol-associated stimuli capture attention, yet drinkers differ in the precise stimuli that become paired with intoxication. Objectives: Extending our prior work to examine the influence of alcoholism risk factors, we paired abstract visual stimuli with intravenous alcohol delivered covertly and examined brain responses to these Pavlovian conditioned stimuli in fMRI when subjects were not intoxicated. Methods: Sixty healthy drinkers performed task-irrelevant alcohol conditioning that presented geometric shapes as conditioned stimuli. Shapes were paired with a rapidly rising alcohol limb (CS+) using intravenous alcohol infusion targeting a final peak breath alcohol concentration of 0.045 g/dL or saline (CS−) infusion at matched rates. On day two, subjects performed monetary delay discounting outside the scanner to assess delay tolerance and then underwent event-related fMRI while performing the same task with CS+, CS−, and an irrelevant symbol. Results: CS+ elicited stronger activation than CS− in frontoparietal executive/attention and orbitofrontal reward-associated networks. Risk factors including family history, recent drinking, sex, and age of drinking onset did not relate to the [CS+ > CS−] activation. Delay-tolerant choice and [CS+ > CS−] activation in right inferior parietal cortex were positively related. Conclusions: Networks governing executive attention and reward showed enhanced responses to stimuli experimentally paired with intoxication, with the right parietal cortex implicated in both alcohol cue pairing and intertemporal choice. While different from our previous study results in 14 men, we believe this paradigm in a large sample of male and female drinkers offers novel insights into Pavlovian processes less affected by idiosyncratic drug associations

Negative urgency and ventromedial prefrontal cortex responses to alcohol cues: FMRI evidence of emotion-based impulsivity

BACKGROUND: Recent research has highlighted the role of emotion-based impulsivity (negative and positive urgency personality traits) for alcohol use and abuse, but has yet to examine how these personality traits interact with the brain's motivational systems. Using functional magnetic resonance imaging (fMRI), we tested whether urgency traits and mood induction affected medial prefrontal responses to alcohol odors (AcO). METHODS: Twenty-seven social drinkers (mean age = 25.2, 14 males) had 6 fMRI scans while viewing negative, neutral, or positive mood images (3 mood conditions) during intermittent exposure to AcO and appetitive control (AppCo) aromas. RESULTS: Voxel-wise analyses (p AppCo] activation throughout medial prefrontal cortex (mPFC) and ventromedial PFC (vmPFC) regions. Extracted from a priori mPFC and vmPFC regions and analyzed in Odor (AcO, AppCo) × Mood factorial models, AcO activation was greater than AppCo in left vmPFC (p AppCo] activation. Negative urgency also mediated the relationship between vmPFC activation and both (i) subjective craving and (ii) problematic drinking. CONCLUSIONS: The trait of negative urgency is associated with neural responses to alcohol cues in the vmPFC, a region involved in reward value and emotion-guided decision-making. This suggests that negative urgency might alter subjective craving and brain regions involved in coding reward value

Correlation between Ventromedial Prefrontal Cortex Activation to Food Aromas and Cue-driven Eating: An fMRI Study

Food aromas are signals associated with both food's availability and pleasure. Previous research from this laboratory has shown that food aromas under fasting conditions evoke robust activation of medial prefrontal brain regions thought to reflect reward value (Bragulat, et al. 2010). In the current study, eighteen women (eleven normal-weight and seven obese) underwent a two-day imaging study (one after being fed, one while fasting). All were imaged on a 3T Siemens Trio-Tim scanner while sniffing two food (F; pasta and beef) odors, one non-food (NF; Douglas fir) odor, and an odorless control (CO). Prior to imaging, participants rated hunger and perceived odor qualities, and completed the Dutch Eating Behavior Questionnaire (DEBQ) to assess “Externality” (the extent to which eating is driven by external food cues). Across all participants, both food and non-food odors (compared to CO) elicited large blood oxygenation level dependent (BOLD) responses in olfactory and reward-related areas, including the medial prefrontal and anterior cingulate cortex, bilateral orbitofrontal cortex, and bilateral piriform cortex, amygdala, and hippocampus. However, food odors produced greater activation of medial prefrontal cortex, left lateral orbitofrontal cortex and inferior insula than non-food odors. Moreover, there was a significant correlation between the [F > CO] BOLD response in ventromedial prefrontal cortex and “Externality” sub-scale scores of the DEBQ, but only under the fed condition; no such correlation was present with the [NF > CO] response. This suggests that in those with high Externality, ventromedial prefrontal cortex may inappropriately valuate external food cues in the absence of internal hunger

Associations between regional brain physiology and trait impulsivity, motor inhibition, and impaired control over drinking

Trait impulsivity and poor inhibitory control are well-established risk factors for alcohol misuse, yet little is known about the associated neurobiological endophenotypes. Here we examined correlations among brain physiology and self-reported trait impulsive behavior, impaired control over drinking, and a behavioral measure of response inhibition. A sample of healthy drinkers (n = 117) completed a pulsed arterial spin labeling (PASL) scan to quantify resting regional cerebral blood flow (rCBF), as well as measures of self-reported impulsivity (Eysenck I7 Impulsivity scale) and impaired control over drinking. A subset of subjects (n = 40) performed a stop signal task during blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging to assess brain regions involved in response inhibition. Eysenck I7 scores were inversely related to blood flow in the right precentral gyrus. Significant BOLD activation during response inhibition occurred in an overlapping right frontal motor/premotor region. Moreover, impaired control over drinking was associated with reduced BOLD response in the same region. These findings suggest that impulsive personality and impaired control over drinking are associated with brain physiology in areas implicated in response inhibition. This is consistent with the idea that difficulty controlling behavior is due in part to impairment in motor restraint systems

Externalizing personality traits, empathy, and gray matter volume in healthy young drinkers

Externalizing psychopathology has been linked to prefrontal abnormalities. While clinically diagnosed subjects show altered frontal gray matter, it is unknown if similar deficits relate to externalizing traits in non-clinical populations. We used voxel-based morphometry (VBM) to retrospectively analyze the cerebral gray matter volume of 176 young adult social to heavy drinkers (mean age=24.0±2.9, male=83.5%) from studies of alcoholism risk. We hypothesized that prefrontal gray matter volume and externalizing traits would be correlated. Externalizing personality trait components-Boredom Susceptibility-Impulsivity (BS/IMP) and Empathy/Low Antisocial Behaviors (EMP/LASB)-were tested for correlations with gray matter partial volume estimates (gmPVE). Significantly large clusters (pFWE<0.05, family-wise whole-brain corrected) of gmPVE correlated with EMP/LASB in dorsolateral and medial prefrontal regions, and in occipital cortex. BS/IMP did not correlate with gmPVE, but one scale of impulsivity (Eysenck I7) correlated positively with bilateral inferior frontal/orbitofrontal, and anterior insula gmPVE. In this large sample of community-dwelling young adults, antisocial behavior/low empathy corresponded with reduced prefrontal and occipital gray matter, while impulsivity correlated with increased inferior frontal and anterior insula cortical volume. These findings add to a literature indicating that externalizing personality features involve altered frontal architecture

Alcohol Affects the P3 Component of an Adaptive Stop Signal Task ERP

BACKGROUND The P3 component of the event-related potential (ERP) has been particularly useful in alcohol research for identifying endophenotypes of alcohol use disorder (AUD) risk in sober subjects. However, practice and/or fatigue reduces P3 amplitude, limiting the ability to ascertain acute and adaptive effects of alcohol exposure. Here, we report acute alcohol effects on P3 amplitude and latency using an adaptive stop signal task (aSST). METHODS One hundred and forty eight nondependent moderate to heavy social drinkers, age 21 to 27, participated in 2 single-blind, alcohol or placebo, counterbalanced sessions approximately one week apart. During each session, subjects performed an adaptive stop signal task (aSST) at (1) baseline, (2) upon reaching the target 60 mg/dL breath alcohol concentration or at the equivalent time during the placebo session, and (3) approximately 135 minutes later while the breath alcohol concentration was clamped. Here, we report on differences between baseline and first subsequent measurements across the experimental sessions. During each aSST run, the stop signal delay (SSD, the time between stop and go signals) adjusted trial-by-trial based on the subject’s performance. RESULTS The aSST reliably generated a STOP P3 component that did not change significantly with repeated task performance. The pre-infusion SSD distribution was bimodal, with mean values several hundred msec apart (FAST: 153 msec and SLOW: 390 msec). This suggested different response strategies: FAST SSD favoring “going” over “stopping,” and SLOW SSD favoring “stopping” over “going”. Exposure to alcohol at 60 mg/dL differentially affected the amplitude and latency of the STOP P3 according to SSD group. Alcohol significantly reduced P3 amplitude in the SLOW SSD compared to FAST SSD group, but significantly increased P3 latency in the FAST SSD compared to SLOW SSD group. CONCLUSIONS The aSST is a robust and sensitive task for detecting alcohol induced changes in inhibition behavior as measured by the P3 component in a within subject design. Alcohol was associated with P3 component changes which varied by SSD group, suggesting a differential effect as a function of task strategy. Overall, the data support the potential utility of the aSST in the detection of alcohol response related AUD risk