Smaller Area Under The Curve Research Articles

Potassium Loss Promotes Impairments in Insulin Sensitivity in Rats

Clinical observations have associated potassium (K+) wasting with metabolic syndrome and insulin resistance. Chronic alkali ingestion can lead to K+ wasting. The alkali sodium bicarbonate (NaHCO3) is now used commonly in chronic kidney disease (CKD) patients to slow renal functional decline, even in patients without metabolic acidosis. Whether chronic ingestion of alkali like NaHCO3 promotes K+ wasting and loss of insulin sensitivity in CKD remains unknown. We hypothesized that chronic NaHCO3 treatment leads to K+ wasting and impairs insulin sensitivity in a rat model of CKD. To test our hypothesis, 12 male, 12 week old Sprague Dawley (SD) rats underwent a 2/3 nephrectomy and were given 4 weeks to recover prior to being placed on either 0.1M NaHCO3 (n=6) or maintained on tap water (n=6) for 4 weeks. After 4 weeks, rats were given hydrochlorothiazide (HCTZ, 10 mg/kg/day) in the drinking water to promote additional K+ wasting in combination with NaHCO3 or tap water for another 4 weeks. Animals underwent insulin tolerance tests (ITT; 0.75 U/kg insulin i.v.) at 4 and 8 week time points. At the conclusion of the protocol, rats were sacrificed, a terminal blood gas measurement taken, and the remaining remnant kidney harvested. Following 4 weeks of NaHCO3 or tap water there was no difference in the blood glucose response to insulin or in the magnitude of the fall in blood glucose (inverse area under the curve (AUC)) in response to insulin. However, following HCTZ treatment, NaHCO3 treated rats were less sensitive to insulin compared to tap water treated rats (Two-way ANOVA, PRxGroup=0.0005, PTime<0.0001, PInteraction=0.17) and had a smaller AUC (NaHCO3 + HCTZ 1688 ± 815 vs tap water + HCTZ 4002 ± 774; unpaired t-test, p=0.06). To determine if K+ depletion could account for the loss of insulin sensitivity, we placed animals on a low K+ diet for 1 week to deplete total body K+ and then determined insulin sensitivity. 6 naïve male, 10 week old SD rats underwent a baseline ITT and an ITT after 1 week of low K+ diet (0K). There was a significant decrease in plasma K+ (baseline 3.55 ± 0.21 vs 0K 2.71 ± 0.29; paired t-test, p=0.01) and a significant effect of diet and time on the blood glucose response to insulin following dietary K+ restriction (RM Two-way ANOVA, PDiet=0.0004, PTime<0.0001, PInteraction=0.70, PSubjects=0.04). At baseline, fasted blood glucose was 144 ± 9.27 mg/dL and fell to its lowest point of 100 ± 7.05 mg/dL at 60 minutes (min), gradually recovering to 132 ± 4.95 mg/dL by end of study (120 min). In contrast, after 1 week of dietary K+ restriction, fasted blood glucose was 151 ± 5.13 mg/dL and fell to its lowest point of 112 ± 6.15 mg/dL by 40 min and recovered to 142 ± 5.30 mg/dL at 80 min, a level that was sustained until the end of the study. In conjunction with a thiazide, chronic NaHCO3 treatment results in reduced insulin sensitivity in rats. K+ depletion with dietary K+ restriction also results in loss of insulin sensitivity in rats. These data strongly implicate K+ wasting as the cause of reduced insulin sensitivity. These findings suggest that K+ wasting may be a cause of insulin resistance and underscore the importance of access to dietary K+, even for patients with CKD. CKD patients treated with NaHCO3 may be at increased risk due to the K+ wasting effects of alkali, particularly those without prior metabolic acidosis.

Effects of reward magnitude frames on measures of delay discounting in a hypothetical money scenario.

The current study analyzed the effects of three frames of reward magnitude-quantity, volume, and duration-on the rate at which college students discounted hypothetical, delayed monetary rewards. Hypothetical scenarios were presented using the fill-in-the-blank discounting questionnaire and participants made choices between immediate and delayed hypothetical monetary rewards. Scenarios framed the monetary choices as (a) quantity of dollar bills, (b) height (inches) of a stack of dollar bills, and (c) duration of time spent in a hypothetical cash machine to collect dollar bills. For each scenario, participants' subjective values were used to calculate the area under the curve (AuC). Framing resulted in a moderate effect size: The duration frame yielded significantly smaller AuC values compared to the quantity and volume frames. Thus, the framing of reward magnitude was a significant variable in controlling discounting rates for hypothetical, delayed monetary rewards. Subsequent investigations should be aware of the independent effects of the reward magnitude frames on delay discounting rates.

Quantitative evaluation of dexamethasone treatment effects in renal ischemia-reperfusion injury using contrast enhanced ultrasonography in rats.

Renal ischemia-reperfusion (I/R) injury often occurs in various clinical events, and its incidence and mortality have been increasing. To investigate the value of contrast enhanced ultrasonography (CEUS) in the monitoring of dexamethasone in the improvement of renal I/R injury in rats. Eighteen healthy male Sprague-Dawley rats were randomly divided into sham-operated, I/R, and I/R surgery plus dexamethasone treatment (Dexa) groups. In the I/R group 45-minute renal ischemia with 24 h reperfusion period was monitored. Time-intensity curve (TIC)-derived parameters, which included peak value, time to peak (TP), area under the curve (AUC), and mean transit time (MTT) were compared to the blood creatinine, urea, Caspase-1, and NLRP3 levels. The I/R group showed an increased peak value, prolonged TP and MTT, and greater AUC (P < 0.05). The Dexa group showed shorter TP and MTT, and smaller AUC (P < 0.05). Results show that the associations between (i) TP, AUC, and MTT and (ii) creatinine, urea, Caspase-1, and NLRP3 levels were significant (P < 0.05). Dexamethasone can alleviate renal I/R injury in rats, which may be related to the inhibition of NLRP3 and caspase-1. CEUS can quantitatively measure this change, in which the changes in TP, AUC and MMT values have considerable reference values.

Perception of English vowels by Javanese and Sundanese speakers; A mouse-tracking study

Second language (L2) learners often encounter difficulties caused by the interference of their native language (L1). The aim of this study is to examine how the Javanese and Sundanese vowel systems hinder the perception of ten English vowels. Thirty Javanese, thirty Sundanese, and twenty English native speakers participated in a mouse-tracking experiment. Participants were required to identify English vowels corresponding to an auditory token by clicking on one of two word strings presented on a computer screen. According to the Speech Learning Model (SLM) hypothesis, the Javanese and Sundanese speakers were predicted to have higher error rates and show a larger Area Under the Curve (AUC) for similar vowels (same IPA symbols, but different diacritics between L1 and the target vowels) than the native English speakers. For new vowels (no same IPA symbols found between L1 and the target vowels), the L2 speakers were predicted to have lower error rates and a smaller AUC than the native English speakers. According to the Second Language Linguistic Perception (L2LP), however, the prediction is stated in the reverse. Repeated measures of ANOVAs found that: 1) the Javanese and Sundanese speakers were less accurate in perceiving the new vowels /ɑː/, /ʌ/, /ae/, /e/, /ɪ/, and /ʊ/ and similar vowels /iː/ and /uː/. 2) The Javanese speakers showed a larger AUC than native speakers for new vowels /ɑː/, /ɜː/, /ɔː/, and /ʌ/ and for similar vowels /iː/ and /uː/. The Sundanese speakers showed a greater attraction to the incorrect alternatives than the native speakers for new vowels /ɑː/, /ɜː/, /ɔː/, /ʌ/, /ae/, /e/, /ɪ/, and /ʊ/ and similar vowels /iː/ and /uː/. Our findings partially support the L2LP hypothesis that the Javanese and Sundanese listeners are likely to show high error rates and a large attraction towards the incorrect alternatives of new vowels. The results confirmed that perceptual difficulties varied significantly according to the influence of L1 vowel inventories.

Clinical value of Fluorine-18-fluorodeoxyglucose PET/CT examination to predict the prognosis of patients after colorectal cancer operation

Objective To investigate the clinical value of Fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT examination to predict the prognosis of patients after colorectal cancer operation. Methods The retrospective cross-sectional study was adopted. The clinicopathological data of 80 patients with colorectal cancer who were admitted to the First Hospital of Nanjing Medical University from March 2007 to October 2015 were collected. Eighty patients received first preoperative 18F-FDG PET/CT examination and underwent operations under decisions of patients and their families, and then adjuvant chemotherapy were performed according to the patients′ condition. Observation indicators included: (1) preoperative imaging examination, (2) situations of treatment and follow-up, (3) analysis of prognostic factors. The patients were followed up by outpatient examination and telephone interview once every 3 months within postoperative 1 year, once every half a year within postoperative 2 years and then once a year up to May 2016. The follow-up included tumor recurrence or progression and survival of patients. Tumor-free survival time was from postoperative day 1 to tumor recurrence or progression and death or end of follow-up. Overall survival time was from postoperative day 1 to death or end of follow-up. Measurement data with skewed distribution were represented as M (Qn) and M (range). The optimal cutoff point of tumor-free survival of maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolism of volume (MTV) and total lesion of glycolysis (TLG) were investigated using the ROC curve analysis, and calculating area under the curve (AUC). The median was used as a cutoff point if there was smaller AUC. The Kaplan-Meier method and Log-rank test were respectively used for survival analysis and univariate analysis, and COX proportional hazards model for multivariate analysis. Results (1) Results of preoperative imaging examination: results of PET/CT in patients with colorectal cancer showed there were circumscribed thickening of bowel wall, intestinal cavity strictures, fuzzy fat space around the some lesions, enlarged lymph node and 18F-FDG uptake increased abnormally. The SUVmax, SUVmean, MTV and TLG of 80 patients were 11.83(4.26, 35.42), 7.06(2.38, 20.92), 20.47 cm3(1.29 cm3, 161.50 cm3) and 138.58(14.17, 857.89), respectively. ROC curve showed that the AUC of SUVmax , SUVmean, MTV and TLG were 0.453, 0.448, 0.815 and 0.749 [95% confidence interval (CI): 0.307-0.600, P>0.05; 0.303-0.594, P>0.05; 0.717- 0.913, P<0.05; 0.635- 0.863, P<0.05], respectively. The median SUVmax (11.83) and SUVmean(7.06) were used as the cutoff points due to smaller AUC of SUVmax and SUVmean. The cutoff point of MTV was 18.79 cm3 (sensitivity=86.2% and specificity=68.3%), and the cutoff point of TLG was 142.05 (sensitivity=75.9% and specificity=70.7%). (2) Situations of treatment and follow-up: among 80 patients, 13 underwent the radical resection of colorectal cancer and resection of liver metastasis and 67 underwent radical resection of colorectal cancer. Sixty-two patients received postoperative chemotherapy, including 45 with chemotherapy regimens of capecitabine and 17 with fluorouracil. Eighty patients were followed up for 41.8 months (range, 6.5-109.1 months ). During the follow-up, 29 patients had tumor recurrence or progression, and 19 patients were dead. The median tumor-free survival time, 1-, 3- and 5-year tumor-free survival rates in 80 patients were 19.5 months (range, 2.0-109.1 months), 73.7%, 36.3% and 18.8%, respectively. The median overall survival time, 1-, 3- and 5-year overall survival rates were 31.8 months (range, 3.3-109.1 months), 76.3%, 37.5% and 20.0%, respectively. (3) Analysis of prognostic factors: results of univariate analysis showed that tumor location, N staging, M staging, clinical staging, postoperative chemotherapy, MTV and TLG were relative factors affecting postoperative tumor-free survival rate (HR=3.469, 5.325, 5.295, 8.605, 2.630, 7.388, 5.155, 95% CI: 1.522-7.906, 2.256-12.568, 2.405-11.657, 2.969-24.937, 1.063-6.504, 2.550-21.403, 2.178-12.204, P<0.05). The tumor location, tumor differentiation, N staging, M staging, clinical staging, MTV and TLG were relative factors affecting postoperative overall survival rate (HR=2.697, 2.814, 3.083, 2.916, 4.193, 5.450, 4.876, 95% CI: 1.011-7.197, 1.121-7.062, 1.166-8.149, 1.140-7.454, 1.386-12.678, 1.581-18.786, 1.727-13.766, P<0.05). In multivariate analysis, stage Ⅲ-Ⅳ of clinical staging and TLG≥142.05 were independent risk factors affecting postoperative tumor-free survival rate (HR=9.879, 3.569, 95% CI: 1.854-22.836, 1.127-11.306, P<0.05). The stage M1, stage Ⅲ-Ⅳ of clinical staging and TLG≥142.05 were independent risk factors affecting postoperative overall survival rate (HR=4.522, 9.315, 10.120, 95% CI: 1.223-16.717, 1.338-24.864, 2.385-12.947, P<0.05). Conclusion TLG through 18F-FDG PET/CT examination is an independent prognostic factor affecting postoperative tumor-free survival rate and overall survival rate in patients with colorectal cancer after curative resection, and it has certainly reference value for prognosis. Key words: Colorectal neoplasms; Prognosis; Tomography, emission-computed; Tomography, X-ray computed; Deoxyglucose

Heroin delay discounting: Modulation by pharmacological state, drug-use impulsivity, and intelligence.

Delay discounting (DD) refers to how rapidly an individual devalues goods based on delays to receipt. DD usually is considered a trait variable but can be state dependent, yet few studies have assessed commodity valuation at short, naturalistically relevant time intervals that might enable state-dependent analysis. This study aimed to determine whether drug-use impulsivity and intelligence influence heroin DD at short (ecologically relevant) delays during two pharmacological states (heroin satiation and withdrawal). Out-of-treatment, intensive heroin users (n = 170; 53.5% African American; 66.7% male) provided complete DD data during imagined heroin satiation and withdrawal. Delays were 3, 6, 12, 24, 48, 72, and 96 hours; maximum delayed heroin amount was thirty $10 bags. Indifference points were used to calculate area under the curve (AUC). We also assessed drug-use impulsivity (subscales from the Impulsive Relapse Questionnaire [IRQ]) and estimated intelligence (Shipley IQ) as predictors of DD. Heroin discounting was greater (smaller AUC) during withdrawal than satiation. In regression analyses, lower intelligence and IRQ Capacity for Delay as well as higher IRQ Speed (to return to drug use) predicted greater heroin discounting in the satiation condition. Lower intelligence and higher IRQ Speed predicted greater discounting in the withdrawal condition. Sex, race, substance use variables, and other IRQ subscales were not significantly related to the withdrawal or satiation DD behavior. In summary, heroin discounting was temporally rapid, pharmacologically state dependent, and predicted by drug-use impulsivity and estimated intelligence. These findings highlight a novel and sensitive measure of acute DD that is easy to administer.

Cost-Effectiveness Analysis of an Early-Initiated, Continuous Chain of Rehabilitation after Severe Traumatic Brain Injury

The aim of this study is to estimate the long-term cost-effectiveness of two different rehabilitation trajectories after severe traumatic brain injury (sTBI). A decision tree model compared hospitalization costs, health effects, and incremental cost-effectiveness ratios (ICER) of a continuous chain versus a broken chain of rehabilitation. The expected costs were estimated by the reimbursement system using diagnosis-related group and based on point estimates of the Disability Rating Scale (DRS); the health effects were measured by means of area under the curve (AUC). The incremental health benefit was estimated as the difference in the AUCs between the chains. Lower values on the DRS scale indicate better health; thus, smaller AUCs were preferred. The modeled population was a cohort of 59 patients with sTBI (30 in continuous chain; 29 in broken chain) with 6-weeks, 1-year, and 5-year post-injury follow-ups. Regarding the DRS estimates, 5-year AUCs were 19.40 (continuous chain) and 23.46 (broken chain). Across 5 years, the continuous chain of rehabilitation had lower costs and better health effects. By replacing the broken chain with the continuous chain, NOK 37.000 could be saved and 4.06 DRS points gained. By means of probabilistic sensitivity analysis, the majority of ICER estimates (67% of the Monte Carlo simulations) indicated that a continuous chain of rehabilitation was less costly and more effective. These findings indicate that the trajectory of continuous rehabilitation represents a dominant strategy in that it reduces costs and improves outcomes after sTBI under reasonable assumptions.

Contingent negative variation is associated with cognitive dysfunction and secondary progressive disease course in multiple sclerosis.

Background and PurposeThe relationship between contingent negative variation (CNV), which is an event-related potential, and cognition in multiple sclerosis (MS) has not been examined previously. The primary objective of the present study was thus to determine the association between CNV and cognition in a sample of MS patients.MethodsThe subjects of this study comprised 66 MS patients [50 with relapsing-remitting MS (RRMS) and 16 with secondary progressive MS (SPMS)] and 40 matched healthy volunteers. A neuropsychological battery was administered to all of the subjects; CNV recordings were made from the Cz, Fz, and Pz electrodes, and the amplitude and area under the curve (AUC) were measured at each electrode.ResultsRRMS patients exhibited CNVs with lower amplitudes and smaller AUCs than the controls at Pz. SPMS patients exhibited CNVs with lower amplitudes and smaller AUCs than the controls, and CNVs with a smaller amplitude than the RRMS patients at both Cz and Pz. After correcting for multiple comparisons, a lower CNV amplitude at Pz was significantly associated with worse performance on measures of speed of information processing, verbal fluency, verbal learning, and verbal recall.ConclusionsCNV may serve as a marker for disease progression and cognitive dysfunction in MS. Further studies with larger samples and wider electrode coverage are required to fully assess the value of CNV in these areas.

A comparison of nine scales to detect depression in Parkinson disease

The Methods of Optimal Depression Detection in Parkinson's Disease (MOOD-PD) study compared the psychometric properties of 9 depression scales to provide guidance on scale selection in Parkinson disease (PD). Patients with PD (n = 229) from community-based neurology practices completed 6 self-report scales (Beck Depression Inventory [BDI]-II, Center for Epidemiologic Studies Depression Rating Scale-Revised [CESD-R], 30-item Geriatric Depression Scale [GDS-30], Inventory of Depressive Symptoms-Patient [IDS-SR], Patient Health Questionnaire-9 [PHQ-9], and Unified Parkinson's Disease Rating Scale [UPDRS]-Part I) and were administered 3 clinician-rated scales (17-item Hamilton Depression Rating Scale [HAM-D-17], Inventory of Depressive Symptoms-Clinician [IDS-C], and Montgomery-Åsberg Depression Rating Scale [MADRS] and a psychiatric interview. DSM-IV-TR diagnoses were established by an expert panel blinded to the self-reported rating scale data. Receiver operating characteristic curves were used to estimate the area under the curve (AUC) of each scale. All scales performed better than chance (AUC 0.75-0.85). Sensitivity ranged from 0.66 to 0.85 and specificity ranged from 0.60 to 0.88. The UPDRS Depression item had a smaller AUC than the BDI-II, HAM-D-17, IDS-C, and MADRS. The CESD-R also had a smaller AUC than the MADRS. The remaining AUCs were statistically similar. The GDS-30 may be the most efficient depression screening scale to use in PD because of its brevity, favorable psychometric properties, and lack of copyright protection. However, all scales studied, except for the UPDRS Depression, are valid screening tools when PD-specific cutoff scores are used.

Selective Serotonin Reuptake Inhibitors and Intraoperative Blood Pressure

The influence of selective serotonin reuptake inhibitors (SSRIs) on blood pressure is poorly understood. We hypothesized that if SSRIs have an influence on blood pressure, this might become manifest in changes in intraoperative blood pressure. We aimed to study the association between perioperative use of SSRIs and changes in intraoperative blood pressure by measuring the occurrence of intraoperative hyper- and hypotension. We conducted a retrospective observational follow-up study among patients who underwent elective primary total hip arthroplasty. The index group included users of SSRIs. The reference group included a random sample (ratio 1:3) of nonusers of an antidepressant agent. The outcome was the occurrence of intraoperative hypo- and hypertensive episodes (number, mean and total duration, and area under the curve (AUC)). The outcome was adjusted for confounding factors using regression techniques. The index group included 20 users of an SSRI. The reference group included 60 nonusers. Users of SSRIs showed fewer intraoperative hypotensive episodes, a shorter mean and total duration, and a smaller AUC when compared to the reference group. After adjustment for confounders, SSRI use was associated with a significantly shorter total duration of hypotension: mean difference of -29.4 min (95% confidence interval (CI) -50.4 to -8.3). Two users of an SSRI and two patients in the reference group had a hypertensive episode. Continuation of treatment with SSRIs before surgery was associated with a briefer duration of intraoperative hypotension.