Acute Ketone Monoester Supplementation Impairs 20-min Time-Trial Performance in Trained Cyclists: A Randomized, Crossover Trial.

Acute ketone monoester (KE) supplementation can alter exercise responses, but the performance effect is unclear. The limited and equivocal data to date are likely related to factors including the KE dose, test conditions, and caliber of athletes studied. We tested the hypothesis that mean power output during a 20-min cycling time trial (TT) would be different after KE ingestion compared to a placebo (PL). A sample size of 22 was estimated to provide 80% power to detect an effect size dz of 0.63 at an alpha level of .05 with a two-tailed paired t test. This determination considered 2.0% as the minimal important difference in performance. Twenty-three trained cyclists (N = 23; peak oxygen uptake: 65 ± 12 ml·kg-1 min-1; M ± SD), who were regularly cycling >5 hr/week, completed a familiarization trial followed by two experimental trials. Participants self-selected and replicated their diet and exercise for ∼24 hr before each trial. Participants ingested either 0.35 g/kg body mass of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate KE or a flavor-matched PL 30 min before exercise in a randomized, triple-blind, crossover manner. Exercise involved a 15-min warm-up followed by the 20-min TT on a cycle ergometer. The only feedback provided was time elapsed. Preexercise venous [ß-hydroxybutyrate] was higher after KE versus PL (2.0 ± 0.6 vs. 0.2 ± 0.1 mM, p < .0001). Mean TT power output was 2.4% (0.6% to 4.1%; mean [95% confidence interval]) lower after KE versus PL (255 ± 54 vs. 261 ± 54 W, p < .01; dz = 0.60). The mechanistic basis for the impaired TT performance after KE ingestion under the present study conditions remains to be determined.

Confirmatory Middle Cerebral Artery Doppler Testing in Alloimmunized Patients with Suspected Fetal Anemia.

OBJECTIVE: This article aimed to evaluate pregnancy outcomes when a plan to perform fetal blood sampling (FBS) or delivery was based solely on the first abnormal middle cerebral artery peak velocity (MCA-PV) measurement compared with making a plan after a confirmatory test on a subsequent day. STUDY DESIGN: We performed a descriptive study of pregnancy outcomes including all patients in a single healthcare system with maternal red cell alloimmunization undergoing ultrasound between 2005 and 2017 who had at least one MCA-PV>1.5 multiples of the median (MoM). We excluded patients with any sign of hydrops prior to the index visit or abnormal MCA-PV at>35 weeks. The first exam with a MCA-PV>1.5 MoM was deemed the index visit. RESULTS: Fifty patients were identified. Twenty-one patients underwent intervention (FBS or delivery) based on the first abnormal MCA-PV. Of those, 9 had moderate or severe anemia (positive predictive value [PPV]: 43%), while 12 had mild or no anemia. The other 29 patients underwent a confirmatory MCA test between 2 and 8 days later. Of these, 13 patients had an abnormal confirmatory test and 11 of these underwent FBS and 7 had moderate or severe anemia (PPV: 54%). Sixteen patients undergoing confirmatory MCA Doppler had a normal test on repeat and did not undergo FBS. Of those, none developed moderate or severe anemia. CONCLUSION: A substantial number of patients (55%) had normal MCA-PV testing on repeat, allowing avoidance of invasive testing. Deferring FBS until the abnormal MCA-PV was confirmed was not associated with undetected moderate or severe anemia. KEY POINTS: · False-positive results from MCA-PV Doppler prediction of fetal anemia are common.. · Repeat noninvasive testing is normal in many patients with suspected fetal anemia.. · Invasive fetal testing can often be safely avoided by performing a confirmatory Doppler exam ination..

Twelve weeks of sprint interval training increases peak cardiac output in previously untrained individuals.

INTRODUCTION: Sprint interval training (SIT), characterized by brief bouts of 'supramaximal' exercise interspersed with recovery periods, increases peak oxygen uptake ([Formula: see text]) despite a low total exercise volume. Per the Fick principle, increased [Formula: see text] is attributable to increased peak cardiac output ([Formula: see text]) and/or peak arterio-venous oxygen difference (a-vO2diff). There are limited and equivocal data regarding the physiological basis for SIT-induced increases in [Formula: see text], with most studies lasting ≤ 6 weeks. PURPOSE: To determine the effect of 12 weeks of SIT on [Formula: see text], measured using inert gas rebreathing, and the relationship between changes in [Formula: see text] and [Formula: see text]. METHODS: 15 healthy untrained adults [6 males, 9 females; 21 ± 2 y (mean ± SD)] performed 28 ± 3 training sessions. Each session involved a 2-min warm-up at 50 W, 3 × 20-s 'all-out' cycling bouts (581 ± 221 W) interspersed with 2-min of recovery, and a 3-min cool-down at 50 W. RESULTS: Measurements performed before and after training showed that 12 weeks of SIT increased [Formula: see text] (17.0 ± 3.7 vs 18.1 ± 4.6 L/min, p = 0.01, partial η2 = 0.28) and [Formula: see text] (2.63 ± 0.78 vs 3.18 ± 1.1 L/min, p < 0.01, partial η2 = 0.58). The changes in these two variables were correlated (r2 = 0.46, p < 0.01). Calculated peak a-vO2diff also increased after training (154 ± 22 vs 174 ± 23 ml O2/L; p < 0.01) and was correlated with the change in [Formula: see text] (r2 = 0.33, p = 0.03). Exploratory analyses revealed an interaction (p < 0.01) such that [Formula: see text] increased in male (+ 10%, p < 0.01) but not female participants (+ 0.6%, p = 0.96), suggesting potential sex-specific differences. CONCLUSION: Twelve weeks of SIT increased [Formula: see text] by 6% in previously untrained participants and the change was correlated with the larger 21% increase in [Formula: see text].

Emergency-release blood transfusions after postpartum hemorrhage at the Intermountain Healthcare hospitals.

BACKGROUND: Most low-risk obstetric patients do not have crossmatched blood available to treat unexpected postpartum hemorrhage. An emergency-release blood transfusion (ERBT) program is critical for hospitals with obstetrical services. We performed a retrospective analysis of obstetrical ERBTs administered in our multihospital system. DESIGN AND METHODS: We collected data from the past 8 years at all Intermountain Healthcare hospitals on every ERBT after postpartum hemorrhage; logging circumstances, number and type of transfused products, and outcomes. RESULTS: Eighty-nine women received ERBT following 224,035 live births, for an incidence of 3.97 transfused women/10,000 births. The most common causally-associated conditions were: uterine atony (40%), placental abruption/placenta previa (16%), retained placenta (11%), and uterine rupture (5%). The mean number of total units transfused was 7.9 (range 1-76). The mean number of red blood cells (RBCs) transfused was 4.8, the median 4, and SD was ±4.4. Massive transfusion protocols (MTPs) for trauma recommend using a ratio of 1:1:1 or 2:1:1 of RBC:FFP:Platelets, however the ratios varied widely for postpartum hemorrhage. Only 1.5% received a 1:1:1 ratio and 7.5% received a 2:1:1 ratio. Nineteen percent (17/89) of women underwent hysterectomy, 7% (6/89) had uterine artery embolization, 36% (32/89) had an intensive care unit admission, and 1% (1/89) died. CONCLUSION: Emergency transfusion for postpartum hemorrhage occurred after 1/2500 births. Most women received less FFP and platelets than recommended for traumatic hemorrhage. A potentially better practice for postpartum hemorrhage would be a balanced ratio of blood products, transfusion of low-titer, group O, cold-stored, whole blood, or inclusion in a MTP.

Unusual Circumstances and Additional Procedures for Fetal Evaluation in Labor.

This chapter describes several circumstances in which the interpretation of the intrapartum fetal heart rate pattern falls outside the usual frame of reference. This includes a more extensive discussion of causes of tachycardia and bradycardia. Ways in which a fetal dysrhythmia may manifest itself in the context of heart rate monitoring are described. Finally, the chapter reviews technological innovations designed to clarify the fetal status when compromise is suspected from the fetal heart rate pattern.

Anticipatory Corticosteroid Administration to Asymptomatic Women with a Short Cervix.

OBJECTIVE: A short cervix is an important risk factor for spontaneous preterm birth. There is substantial evidence that antenatal exposure to corticosteroids significantly benefits infants that are born when delivery occurs between 24 and 34 weeks' gestation and after 48 hours but within 7 days of their administration. Our study was to evaluate whether asymptomatic women who are given a course of antenatal corticosteroids (ACS) at the time a short cervix is identified deliver within the window of proven steroid benefit. STUDY DESIGN: This was a retrospective chart review of patients who had a cervical length of < 2.5 cm between 23 and 34 weeks and who did not have cervical dilation or significant symptoms of preterm labor. RESULTS: Of 367 asymptomatic patients with a short cervix, only two (0.5%) delivered within 7 days of the time a short cervix was identified. With a policy of giving ACS at the time an ultrasound shows a short cervix, 184 patients would have to be treated for each one who realizes a steroid benefit by delivering within 7 days. CONCLUSION: We conclude that unless future studies show that neonates benefit from ACS given more than 7 days before delivery, giving ACS to asymptomatic women solely because the cervix is short is not advised.

Accuracy of ultrasound for the prediction of placenta accreta.

OBJECTIVE: Ultrasound has been reported to be greater than 90% sensitive for the diagnosis of accreta. Prior studies may be subject to bias because of single expert observers, suspicion for accreta, and knowledge of risk factors. We aimed to assess the accuracy of ultrasound for the prediction of accreta. STUDY DESIGN: Patients with accreta at a single academic center were matched to patients with placenta previa, but no accreta, by year of delivery. Ultrasound studies with views of the placenta were collected, deidentified, blinded to clinical history, and placed in random sequence. Six investigators prospectively interpreted each study for the presence of accreta and findings reported to be associated with its diagnosis. Sensitivity, specificity, positive predictive, negative predictive value, and accuracy were calculated. Characteristics of accurate findings were compared using univariate and multivariate analyses. RESULTS: Six investigators examined 229 ultrasound studies from 55 patients with accreta and 56 controls for 1374 independent observations. 1205/1374 (87.7% overall, 90% controls, 84.9% cases) studies were given a diagnosis. There were 371 (27.0%) true positives; 81 (5.9%) false positives; 533 (38.8%) true negatives, 220 (16.0%) false negatives, and 169 (12.3%) with uncertain diagnosis. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 53.5%, 88.0%, 82.1%, 64.8%, and 64.8%, respectively. In multivariate analysis, true positives were more likely to have placental lacunae (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.4-1.6), loss of retroplacental clear space (OR, 2.4; 95% CI, 1.1-4.9), or abnormalities on color Doppler (OR, 2.1; 95% CI, 1.8-2.4). CONCLUSION: Ultrasound for the prediction of placenta accreta may not be as sensitive as previously described.

Interobserver variability of sonography for prediction of placenta accreta.

OBJECTIVES: The sensitivity of sonography to predict accreta has been reported as higher than 90%. However, most studies are from single expert investigators. Our objective was to analyze interobserver variability of sonography for prediction of placenta accreta. METHODS: Patients with previa with and without accreta were ascertained, and images with placental views were collected, deidentified, and placed in random sequence. Three radiologists and 3 maternal-fetal medicine specialists interpreted each study for the presence of accreta and specific findings reported to be associated with its diagnosis. Investigator-specific sensitivity, specificity, and accuracy were calculated. κ statistics were used to assess variability between individuals and types of investigators. RESULTS: A total of 229 sonographic studies from 55 patients with accreta and 56 control patients were examined. Accuracy ranged from 55.9% to 76.4%. Of imaging studies yielding diagnoses, sensitivity ranged from 53.4% to 74.4%, and specificity ranged from 70.8% to 94.8%. Overall interobserver agreement was moderate (mean κ ± SD = 0.47 ± 0.12). κ values between pairs of investigators ranged from 0.32 (fair agreement) to 0.73 (substantial agreement). Average individual agreement ranged from fair (κ = 0.35) to moderate (κ = 0.53). CONCLUSIONS: Blinded from clinical data, sonography has significant interobserver variability for the diagnosis of placenta accreta.

Tachysystole in term labor: incidence, risk factors, outcomes, and effect on fetal heart tracings.

OBJECTIVE: Recent recommendations called for obstetricians to abandon the terms of "hyperstimulation" and "hypercontractility" in favor of the more rigidly defined term, "tachysystole" (TS). The aim of the current study is to describe incidence of and risk factors for TS, describe fetal heart rate (FHR) changes associated with TS, and investigate maternal and neonatal outcomes associated with TS. STUDY DESIGN: For this retrospective cohort study, we reviewed and analyzed the intrapartum FHR and tocometric characteristics of all patients with a singleton, nonanomalous fetus in term labor in a single hospital system over a 28-month period. Univariate association testing was done using χ(2) and t tests, comparing demographics, pregnancy characteristics, outcomes, and TS events. Multivariable association testing between risk factors and TS events were tested using generalized estimating equations, adjusting for multiple pregnancies during the study period for the same woman. RESULTS: There were a total of 50,335 deliveries from 48,529 women during the 28-month period. Of these, there were a total of 7567 TS events in 5363 deliveries among 5332 women. Use of oxytocin or misoprostol, an epidural, hypertension, and induction of labor were associated with an increased risk of TS. We found a doubling of TS events with any oxytocin, a dose-response correlation between oxytocin and TS, FHR changes occurring in a quarter of TS events and, finally, that presence of TS increases the chance of composite neonatal morbidity. CONCLUSION: TS is associated with specific risk factors and impacts FHR and neonatal morbidity.

Fetal umbilical vein deviation in congenital diaphragmatic hernia.

OBJECTIVES: Deviation of the intra-abdominal umbilical vein has been described as a marker of congenital diaphragmatic hernia (CDH) and has been shown to help identify liver herniation into the fetal chest. The purpose of this study was to quantify the degree of deviation in affected fetuses and to determine the accuracy of measurements for diagnosing liver herniation. METHODS: In patients undergoing prenatal sonography for CDH, the midhepatic portion of the umbilical vein was identified, and the distance between the lateral edge of the vein and the inner rib margin was measured. The same was done on the right, and the ratio of the left to right measurement was termed the "umbilical vein ratio." The accuracy of the umbilical vein ratio for predicting the presence and side of the hernia and for diagnosing liver herniation was determined. RESULTS: All but 1 of the cases with right-sided hernias had an umbilical vein ratio above the normal range, and all had liver herniation. Of those with a left-sided hernia, only 2 had a ratio within the normal range. Of those with a left-sided hernia, an umbilical vein ratio less than 0.4 was shown by receiver operating characteristic curve analysis to be the best predictor of liver herniation. This cutoff had sensitivity of 89% for predicting herniation, with a false-positive rate of 14%. CONCLUSIONS: Ninety-three percent of right-sided CDH lesions and 98% of left-sided lesions have an umbilical vein ratio outside the normal range. This finding shows that deviation may a useful indicator of CDH in screening ultrasound examinations. An umbilical vein ratio less than 0.4 is predictive of liver herniation.

Peak Cardiac Output Determined Using Inert Gas Rebreathing: A Comparison of Two Exercise Protocols.

PURPOSE: This study aimed to compare Q˙peak elicited by a constant load protocol ( Q˙CL ) and an incremental step protocol ( Q˙step ). METHODS: A noninferiority randomized crossover trial was used to compare Q˙peak between protocols using a noninferiority margin of 0.5 L·min -1 . Participants ( n = 34 (19 female, 15 male); 25 ± 5 yr) performed two baseline V̇O 2peak tests to determine peak heart rate (HR peak ) and peak work rate ( Wpeak ). Participants then performed the Q˙CL and Q˙step protocols each on two separate occasions with the order of the four visits randomized. Q˙peak was measured using IGR (Innocor; COSMED, Rome, Italy). The Q˙CL protocol involved a V̇O 2peak test followed 10 min later by cycling at 90% Wpeak , with IGR initiated after 2 min. Q˙step involved an incremental step test with IGR initiated when the participant's HR reached 5 bpm below their HR peak . The first Q˙CL and Q˙step tests were compared for noninferiority, and the second series of tests was used to measure repeatability (typical error (TE)). RESULTS: The Q˙CL protocol was noninferior to Q˙step ( Q˙CL = 17.1 ± 3.2, Q˙step = 16.8 ± 3.1 L·min -1 ; 95% confidence intervals, -0.16 to 0.72 L·min -1 ). The baseline V̇O 2peak (3.13 ± 0.83 L·min -1 ) was achieved during Q˙CL (3.12 ± 0.72, P = 0.87) and Q˙step (3.12 ± 0.80, P = 0.82). The TE values for Q˙peak were 6.6% and 8.3% for Q˙CL and Q˙step , respectively. CONCLUSIONS: The Q˙CL protocol was noninferior to Q˙step and may be more convenient because of the reduced time commitment to perform the measurement.

The effect of bodyweight exercise on 24-h glycemic responses determined by continuous glucose monitoring in healthy inactive adults: a randomized crossover study.

Vigorous intermittent exercise can improve indices of glycemia in the 24 h postexercise period in apparently healthy individuals. We examined the effect of a single session of bodyweight exercise (BWE) on glycemic responses using continuous glucose monitoring (CGM) under controlled dietary conditions. Healthy inactive adults (n = 27; 8 males, 19 females; age: 23 ± 3 years) completed 2 virtually supervised trials spaced ~ 1 week apart in a randomized, crossover manner. The trials involved an 11-min BWE protocol that consisted of 5 × 1-min bouts performed at a self-selected pace interspersed with 1-min active recovery periods or a non-exercise sitting control period (CON). Mean heart rate during the BWE protocol was 147 ± 14 beats per min (75% of age-predicted maximum). Mean 24 h glucose after BWE and CON was not different (5.0 ± 0.4 vs 5.0 ± 0.5 mM respectively; p = 0.39). There were also no differences between conditions for measures of glycemic variability or the postprandial glucose responses after ingestion of a 75 g glucose drink or lunch, dinner, and breakfast meals. This study demonstrates the feasibility of conducting a remotely supervised BWE intervention using CGM under free-living conditions. Future studies should investigate the effect of repeated sessions of BWE training or responses in people with impaired glycemic control.

Effect of Acute Ketone Monoester Ingestion on Cardiorespiratory Responses to Exercise and the Influence of Blood Acidosis.

PURPOSE: This study aimed to examine the effect of KE ingestion on exercise cardiac output ( Q˙ ) and the influence of blood acidosis. We hypothesized that KE versus placebo ingestion would increase Q ˙, and coingestion of the pH buffer bicarbonate would mitigate this effect. METHODS: In a randomized, double-blind, crossover manner, 15 endurance-trained adults (peak oxygen uptake (V̇O 2peak ), 60 ± 9 mL·kg -1 ·min -1 ) ingested either 0.2 g·kg -1 sodium bicarbonate or a salt placebo 60 min before exercise, and 0.6 g·kg -1 KE or a ketone-free placebo 30 min before exercise. Supplementation yielded three experimental conditions: basal ketone bodies and neutral pH (CON), hyperketonemia and blood acidosis (KE), and hyperketonemia and neutral pH (KE + BIC). Exercise involved 30 min of cycling at ventilatory threshold intensity, followed by determinations of V̇O 2peak and peak Q ˙. RESULTS: Blood [ß-hydroxybutyrate], a ketone body, was higher in KE (3.5 ± 0.1 mM) and KE + BIC (4.4 ± 0.2) versus CON (0.1 ± 0.0, P < 0.0001). Blood pH was lower in KE versus CON (7.30 ± 0.01 vs 7.34 ± 0.01, P < 0.001) and KE + BIC (7.35 ± 0.01, P < 0.001). Q ˙ during submaximal exercise was not different between conditions (CON: 18.2 ± 3.6, KE: 17.7 ± 3.7, KE + BIC: 18.1 ± 3.5 L·min -1 ; P = 0.4). HR was higher in KE (153 ± 9 bpm) and KE + BIC (154 ± 9) versus CON (150 ± 9, P < 0.02). V̇O 2peak ( P = 0.2) and peak Q ˙ ( P = 0.3) were not different between conditions, but peak workload was lower in KE (359 ± 61 W) and KE + BIC (363 ± 63) versus CON (375 ± 64, P < 0.02). CONCLUSIONS: KE ingestion did not increase Q ˙ during submaximal exercise despite a modest elevation of HR. This response occurred independent of blood acidosis and was associated with a lower workload at V̇O 2peak .

Biological sex does not influence the peak cardiac output response to twelve weeks of sprint interval training.

Sprint interval training (SIT) increases peak oxygen uptake (V̇O2peak) but the mechanistic basis is unclear. We have reported that 12 wk of SIT increased V̇O2peak and peak cardiac output (Q̇peak) and the changes in these variables were correlated. An exploratory analysis suggested that Q̇peak increased in males but not females. The present study incorporated best practices to examine the potential influence of biological sex on the Q̇peak response to SIT. Male and female participants (n = 10 each; 21 ± 4 y) performed 33 ± 2 sessions of SIT over 12 wk. Each 10-min session involved 3 × 20-s 'all-out' sprints on an ergometer. V̇O2peak increased after SIT (3.16 ± 1.0 vs. 2.89 ± 1.0 L/min, η2p = 0.53, p < 0.001) with no sex × time interaction (p = 0.61). Q̇peak was unchanged after training (15.2 ± 3.3 vs. 15.1 ± 3.0 L/min, p = 0.85), in contrast to our previous study. The peak estimated arteriovenous oxygen difference increased after training (204 ± 30 vs. 187 ± 36 ml/L, p = 0.006). There was no effect of training or sex on measures of endothelial function. We conclude that 12 wk of SIT increases V̇O2peak but the mechanistic basis remains unclear. The capacity of inert gas rebreathing to assess changes in Q̇peak may be limited and invasive studies that use more direct measures are needed.

Increased cardiorespiratory stress during submaximal cycling after ketone monoester ingestion in endurance-trained adults.

There is growing interest in the effect of exogenous ketone body supplementation on exercise responses and performance. The limited studies to date have yielded equivocal data, likely due in part to differences in dosing strategy, increase in blood ketones, and participant training status. Using a randomized, double-blind, counterbalanced design, we examined the effect of ingesting a ketone monoester (KE) supplement (600 mg/kg body mass) or flavour-matched placebo in endurance-trained adults (n = 10 males, n = 9 females; V̇O2peak = 57 ± 8 mL/kg/min). Participants performed a 30-min cycling bout at ventilatory threshold intensity (71 ± 3% V̇O2peak), followed 15 min later by a 3 kJ/kg body mass time-trial. KE versus placebo ingestion increased plasma ß-hydroxybutyrate concentration before exercise (3.9 ± 1.0 vs 0.2 ± 0.3 mM, p < 0.0001, dz = 3.4), ventilation (77 ± 17 vs 71 ± 15 L/min, p < 0.0001, dz = 1.3) and heart rate (155 ± 11 vs 150 ± 11 beats/min, p < 0.001, dz = 1.2) during exercise, and rating of perceived exertion at the end of exercise (15.4 ± 1.6 vs 14.5 ± 1.2, p < 0.01, dz = 0.85). Plasma ß-hydroxybutyrate concentration remained higher after KE vs placebo ingestion before the time-trial (3.5 ± 1.0 vs 0.3 ± 0.2 mM, p < 0.0001, dz = 3.1), but performance was not different (KE: 16:25 ± 2:50 vs placebo: 16:06 ± 2:40 min:s, p = 0.20; dz = 0.31). We conclude that acute ingestion of a relatively large KE bolus dose increased markers of cardiorespiratory stress during submaximal exercise in endurance-trained participants. Novelty: Limited studies have yielded equivocal data regarding exercise responses after acute ketone body supplementation. Using a randomized, double-blind, placebo-controlled, counterbalanced design, we found that ingestion of a large bolus dose of a commercial ketone monoester supplement increased markers of cardiorespiratory stress during cycling at ventilatory threshold intensity in endurance-trained adults.

Deterministic dynamics of neural activity during absence seizures in rats.

The study of brain electrical activities in terms of deterministic nonlinear dynamics has recently received much attention. Forbidden ordinal patterns (FOP) is a recently proposed method to investigate the determinism of a dynamical system through the analysis of intrinsic ordinal properties of a nonstationary time series. The advantages of this method in comparison to others include simplicity and low complexity in computation without further model assumptions. In this paper, the FOP of the EEG series of genetic absence epilepsy rats from Strasbourg was examined to demonstrate evidence of deterministic dynamics during epileptic states. Experiments showed that the number of FOP of the EEG series grew significantly from an interictal to an ictal state via a preictal state. These findings indicated that the deterministic dynamics of neural networks increased significantly in the transition from the interictal to the ictal states and also suggested that the FOP measures of the EEG series could be considered as a predictor of absence seizures.

Intrahepatic complement activation, sinusoidal endothelial injury, and lactic acidosis are associated with initial poor function of the liver after transplantation.

BACKGROUND: Changes in glucose metabolism in the liver during transplantation have been recently described using microdialysis. Here, these findings are correlated with histopathologic, immunohistochemical, and ultrastructural changes in liver. METHODS: Microdialysis catheters were inserted into 15 human livers, which were perfused with isotonic solution, and samples of perfusate were analyzed before harvest, after storage, and after reperfusion. At each stage Menghini needle biopsy samples were taken and each studied using light and electron microscopy. RESULTS: Six livers showed serum biochemical evidence of initial poor function. These livers had significantly more staining for complement fragment 4d (C4d) of both lobular and periportal hepatocytes. C4d-positive hepatocytes were also found in the liver during cold storage (3 of 15). These periportal hepatocytes also showed evidence of necrosis and were found to have intracellular neutrophils. Hepatocyte rounding in zone III, necrosis, and C4d staining in recipient were also significantly correlated with the degree of lactic acidosis during this phase. Intrahepatic lactic acidosis at all time points was significantly associated with sinusoidal endothelial cell injury after reperfusion. There were no correlations between glucose, pyruvate, and glycerol levels and histopathologic changes in the liver. DISCUSSION: In the patients studied, the degree of C4d staining correlated with initial poor function and was associated with intrahepatic lactic acidosis in the donor during cold storage and after reperfusion. Complement activity in the liver during cold storage may be after in situ activation. Intrahepatic lactic acidosis is associated with sinusoidal endothelial cell and hepatocyte injury. The role of intrahepatic neutrophils is uncertain and could possibly be in response to cell necrosis.

Using recurrence plot for determinism analysis of EEG recordings in genetic absence epilepsy rats.

OBJECTIVE: Understanding the transition of brain activity towards an absence seizure is a challenging task. In this paper, we use recurrence quantification analysis to indicate the deterministic dynamics of EEG series at the seizure-free, pre-seizure and seizure states in genetic absence epilepsy rats. METHODS: The determinism measure, DET, based on recurrence plot, was applied to analyse these three EEG datasets, each dataset containing 300 single-channel EEG epochs of 5-s duration. Then, statistical analysis of the DET values in each dataset was carried out to determine whether their distributions over the three groups were significantly different. Furthermore, a surrogate technique was applied to calculate the significance level of determinism measures in EEG recordings. RESULTS: The mean (+/-SD) DET of EEG was 0.177+/-0.045 in pre-seizure intervals. The DET values of pre-seizure EEG data are significantly higher than those of seizure-free intervals, 0.123+/-0.023, (P<0.01), but lower than those of seizure intervals, 0.392+/-0.110, (P<0.01). Using surrogate data methods, the significance of determinism in EEG epochs was present in 25 of 300 (8.3%), 181 of 300 (60.3%) and 289 of 300 (96.3%) in seizure-free, pre-seizure and seizure intervals, respectively. CONCLUSIONS: Results provide some first indications that EEG epochs during pre-seizure intervals exhibit a higher degree of determinism than seizure-free EEG epochs, but lower than those in seizure EEG epochs in absence epilepsy. SIGNIFICANCE: The proposed methods have the potential of detecting the transition between normal brain activity and the absence seizure state, thus opening up the possibility of intervention, whether electrical or pharmacological, to prevent the oncoming seizure.

Maternal and developmental toxicity study of sodium azide in rats.

Sodium azide (NaN(3)) is being proposed for use as an active ingredient to control a broad spectrum of soil borne pathogens including insects, weeds, nematodes, fungi, and bacteria. The purpose of this study was to determine the maternal and developmental toxicity of NaN(3) in rats. Sperm-positive Sprague-Dawley rats were treated with NaN(3) via oral gavage once daily from Gestation Day (GD) 6 through 19 at respective dose levels of 0, 1, 5, and 17.5mg/kg/day. From GD 10-12, the high-dose was reduced to 10mg/kg/day due to maternal mortality. Cesarean section was performed on GD 20 and implantation and resorptions sites, live and dead fetuses were counted. Fetuses were weighed, sexed externally and processed for gross external, visceral and skeletal examinations. A high rate of maternal mortality; reduced gestation body weight, gestation body weight changes and food consumption; decreased corrected body weight and corrected weight gain were observed at 17.5/10mg/kg/day. Fetal weight was also reduced at 17.5/10mg/kg/day. There were no maternal deaths, clinical signs or body weight effects that were considered related to NaN(3) at 1 and 5mg/kg/day. No increase in the incidence of malformations and variations were observed at any of the doses evaluated. Based on the results of this study, the No Observed Adverse Effect Level (NOAEL) and the Lowest Observed Adverse Effect Level (LOAEL) for maternal and developmental toxicity of NaN(3) in rats were considered to be 5 and 17.5/10mg/kg/day, respectively.

Predictability analysis of absence seizures with permutation entropy.

In this study, we investigate permutation entropy as a tool to predict the absence seizures of genetic absence epilepsy rats from Strasbourg (GAERS) by using EEG recordings. The results show that permutation entropy can track the dynamical changes of EEG data, so as to describe transient dynamics prior to the absence seizures. Experiments demonstrate that permutation entropy can successfully detect pre-seizure state in 169 out of 314 seizures from 28 rats and the average anticipation time of permutation entropy is around 4.9s. These findings could shed new light on the mechanism of absence seizure. In comparison with results of sample entropy, permutation entropy is better able to predict absence seizures.