Postoperative splanchnic blood flow redistribution in response to fluid challenges in the presence and absence of endotoxemia in a porcine model

We hypothesized that fluid administration may increase regional splanchnic perfusion after abdominal surgery-even in the absence of a cardiac stroke volume (SV) increase and independent of accompanying endotoxemia. Sixteen anesthetized pigs underwent abdominal surgery with flow probe fitting around splanchnic vessels and carotid arteries. They were randomized to continuous placebo or endotoxin infusion, and when clinical signs of hypovolemia (mean arterial pressure, <60 mmHg; heart rate, >100 beats · min(-1); urine production, <0.5 mL · kg(-1) · h(-1); arterial lactate concentration, >2 mmol · L(-1)) and/or low pulmonary artery occlusion pressure (target 5-8 mmHg) were present, they received repeated boli of colloids (50 mL) as long as SV increased 10% or greater. Stroke volume and regional blood flows were monitored 2 min before and 30 min after fluid challenges. Of 132 fluid challenges, 45 (34%) resulted in an SV increase of 10% or greater, whereas 82 (62%) resulted in an increase of 10% or greater in one or more of the abdominal flows (P < 0.001). During blood flow redistribution, celiac trunk (19% of all measurements) and hepatic artery flow (15%) most often decreased, whereas portal vein (10%) and carotid artery (7%) flow decreased less frequently (P = 0.015, between regions). In control animals, celiac trunk (30% vs. 9%, P = 0.004) and hepatic artery (25% vs. 11%, P = 0.040) flow decreased more often than in endotoxin-infused pigs. Accordingly, blood flow redistribution is a common phenomenon in the postoperative period and is only marginally influenced by endotoxemia. Fluid management based on SV changes may not be useful for improving regional abdominal perfusion.

Immunologic response to antiretroviral therapy in hepatitis C virus-coinfected adults in a population-based HIV/AIDS treatment program

BACKGROUND: We sought to characterize the impact that hepatitis C virus (HCV) infection has on CD4 cells during the first 48 weeks of antiretroviral therapy (ART) in previously ART-naive human immunodeficiency virus (HIV)-infected patients. METHODS: The HIV/AIDS Drug Treatment Programme at the British Columbia Centre for Excellence in HIV/AIDS distributes all ART in this Canadian province. Eligible individuals were those whose first-ever ART included 2 nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor and who had a documented positive result for HCV antibody testing. Outcomes were binary events (time to an increase of > or = 75 CD4 cells/mm3 or an increase of > or = 10% in the percentage of CD4 cells in the total T cell population [CD4 cell fraction]) and continuous repeated measures. Statistical analyses used parametric and nonparametric methods, including multivariate mixed-effects linear regression analysis and Cox proportional hazards analysis. RESULTS: Of 1186 eligible patients, 606 (51%) were positive and 580 (49%) were negative for HCV antibodies. HCV antibody-positive patients were slower to have an absolute (P<.001) and a fraction (P = .02) CD4 cell event. In adjusted Cox proportional hazards analysis (controlling for age, sex, baseline absolute CD4 cell count, baseline pVL, type of ART initiated, AIDS diagnosis at baseline, adherence to ART regimen, and number of CD4 cell measurements), HCV antibody-positive patients were less likely to have an absolute CD4 cell event (adjusted hazard ratio [AHR], 0.84 [95% confidence interval [CI], 0.72-0.98]) and somewhat less likely to have a CD4 cell fraction event (AHR, 0.89 [95% CI, 0.70-1.14]) than HCV antibody-negative patients. In multivariate mixed-effects linear regression analysis, HCV antibody-negative patients had increases of an average of 75 cells in the absolute CD4 cell count and 4.4% in the CD4 cell fraction, compared with 20 cells and 1.1% in HCV antibody-positive patients, during the first 48 weeks of ART, after adjustment for time-updated pVL, number of CD4 cell measurements, and other factors. CONCLUSION: HCV antibody-positive HIV-infected patients may have an altered immunologic response to ART.

Enhancing BOLD response in the auditory system by neurophysiologically tuned fMRI sequence

Auditory neuroscience has not tapped fMRI's full potential because of acoustic scanner noise emitted by the gradient switches of conventional echoplanar fMRI sequences. The scanner noise is pulsed, and auditory cortex is particularly sensitive to pulsed sounds. Current fMRI approaches to avoid stimulus-noise interactions are temporally inefficient. Since the sustained BOLD response to pulsed sounds decreases with repetition rate and becomes minimal with unpulsed sounds, we developed an fMRI sequence emitting continuous rather than pulsed gradient sound by implementing a novel quasi-continuous gradient switch pattern. Compared to conventional fMRI, continuous-sound fMRI reduced auditory cortex BOLD baseline and increased BOLD amplitude with graded sound stimuli, short sound events, and sounds as complex as orchestra music with preserved temporal resolution. Response in subcortical auditory nuclei was enhanced, but not the response to light in visual cortex. Finally, tonotopic mapping using continuous-sound fMRI demonstrates that enhanced functional signal-to-noise in BOLD response translates into improved spatial separability of specific sound representations.

Increased NoGo-anteriorisation in first-episode schizophrenia patients during Continuous Performance Test

OBJECTIVE: NoGo-stimuli during a Continuous Performance Test (CPT) activate prefrontal brain structures such as the anterior cingulate gyrus and lead to an anteriorisation of the positive electrical field of the NoGo-P300 relative to the Go-P300, so-called NoGo-anteriorisation (NGA). NGA during CPT is regarded as a neurophysiological standard index for cognitive response control. While it is known that patients with chronic schizophrenia exhibit a significant reduction in NGA, it is unclear whether this also occurs in patients undergoing their first-episode. Thus, the aim of the present study was to determine NGA in a group of patients with first-episode schizophrenia by utilizing a CPT paradigm. METHODS: Eighteen patients with first-episode schizophrenia and 18 matched healthy subjects were investigated electrophysiologically during a cued CPT, and the parameters of the Go- and NoGo-P300 were determined using microstate analysis. Low resolution tomography analysis (LORETA) was used for source determination. RESULTS: Due to a more posterior Go- and a more anterior NoGo-centroid, NGA was greater in patients than in healthy controls. LORETA indicated the same sources for both groups after Go-stimuli, but a more anterior source in patients after NoGo-stimuli. In patients P300-amplitude responses to both Go- and NoGo-stimuli were decreased, and P300-latency to NoGo-stimuli was increased. After the Go-stimuli false reactions and reaction times were increased in patients. CONCLUSIONS: Attention was reduced in patients with first-episode schizophrenia, as indicated by more false reactions, prolongation of reaction time, P300-latencies and by a decrease in P300-amplitude. Significantly however, the NGA and prefrontal LORETA-sources indicate intact prefrontal brain structures in first-episode schizophrenia patients. Previously described changes in this indicator of prefrontal function may be related to a progressive decay in chronic schizophrenia. SIGNIFICANCE: The results support the idea of a possible new biological marker of first episode psychosis, which may be a useful parameter for the longitudinal measurement of changing prefrontal brain function in a single schizophrenia patient.

Effects of continuous remifentanil administration on intra-operative subcutaneous tissue oxygen tension

Surgical stress response markedly increases sympathetic nerve activity and catecholamine concentrations. This may contribute to peripheral vasoconstriction, reduced wound perfusion and subsequent tissue hypoxia. Opioids are known to depress the hypothalamic-adrenal response to surgery in a dose-dependent manner. We tested the hypothesis that continuous remifentanil administration produces improved subcutaneous tissue oxygen tension compared to fentanyl bolus administration. Forty-six patients undergoing major abdominal surgery were randomly assigned to receive either fentanyl bolus administration or continuous remifentanil infusion. Mean subcutaneous tissue oxygen values over the entire intra-operative period were significantly higher in the remifentanil group, when compared to the fentanyl group: 8 (2) kPa vs 6.7 (1.5) kPa, % CI difference: - 2.3 kPa to - 0.3 kPa, p = 0.013. Continuous intra-operative opioid administration may blunt vasoconstriction caused by surgical stress and adrenergic responses more than an equi-effective anaesthetic regimen based on smaller-dose bolus opioid administration.

Different response to eccentric and concentric training in older men and women

Sarcopenia is the age-related loss of muscle mass and strength and has been associated with an increased risk of falling and the development of metabolic diseases. Various training protocols, nutritional and hormonal interventions have been proposed to prevent sarcopenia. This study explores the potential of continuous eccentric exercise to retard age-related loss of muscle mass and function. Elderly men and women (80.6 +/- 3.5 years) were randomized to one of three training interventions demanding a training effort of two sessions weekly for 12 weeks: cognitive training (CT; n = 16), conventional resistance training (RET; n = 23) and eccentric ergometer training (EET; n = 23). Subjects were tested for functional parameters and body composition. Biopsies were collected from M. vastus lateralis before and after the intervention for the assessment of fiber size and composition. Maximal isometric leg extension strength (MEL: +8.4 +/- 1.7%) and eccentric muscle coordination (COORD: -43 +/- 4%) were significantly improved with EET but not with RET (MEL: +2.3 +/- 2.0%; COORD: -13 +/- 3%) and CT (MEL: -2.3 +/- 2.5%; COORD: -12 +/- 5%), respectively. We observed a loss of body fat (-5.0 +/- 1.1%) and thigh fat (-6.9 +/- 1.5%) in EET subjects only. Relative thigh lean mass increased with EET (+2.5 +/- 0.6%) and RET (+2.0 +/- 0.3%) and correlated negatively with type IIX/type II muscle fiber ratios. It was concluded that both RET and EET are beneficial for the elderly with regard to muscle functional and structural improvements but differ in their spectrum of effects. A training frequency of only two sessions per week seems to be the lower limit for a training stimulus to reveal measurable benefits.

Triangle-programmed coulometric nanotitrations completed by continuous flow with potentiometric detection

Coulometric nanotitrations were realized in a microchannel system using a continuous-flow titration technique with a triangle current-time profile. Redox and acid-base titrations were carried out on Fe(II) and nitric acid samples, respectively, with the same nanotitrator device. A linear relation between the concentration and the coulometric current transferred to the solution was found. The advantages of this universally applicable nanotitrator are fast response, low sample volume, high sensitivity, and high reproducibility as well as the convenience of handling an automated analyzer of the flow-through type.

The influence of a continuous rate infusion of dexmedetomidine on the nociceptive withdrawal reflex and temporal summation during isoflurane anaesthesia in dogs

Objective To examine the influence of a low dose dexmedetomidine infusion on the nociceptive withdrawal reflex and temporal summation in dogs during isoflurane anaesthesia. Study design Prospective experimental blinded cross-over study. Animals Eight healthy mixed breed dogs, body weight Mean +/- SD 26.5 +/- 8.4 kg and age 25 +/- 16 months. Methods Anaesthesia was induced with propofol and maintained with isoflurane (Fe'ISO 1.3%) delivered in oxygen and air. After stabilization, baseline recordings (time 0) were obtained, then a dexmedetomidine bolus (1 mug kg(-1) IV) followed by a continuous rate infusion (1 mug kg(-1) hour(-1) ) or saline placebo were administered. At times 10, 30 and 60 minutes after the initial bolus, electrical stimulations of increasing intensity were applied over the lateral plantar digital nerve, and administered both as single and as repeated stimuli. The resulting reflex responses were recorded using electromyography. Data were analysed using a multivariable linear regression model and a Kruskal Wallis test for single stimulation data, and repeated measures anova and paired t-test for repeated stimulation data. Results The AUC for the stimulus-response curves after single stimulation were similar for both treatments at time 0. At times 10, 30 and 60 the AUCs for the stimulus-response curves were significantly lower with dexmedetomidine treatment than with placebo. Temporal summation was evident in both treatments at times 0, 10, 30 and 60 starting from a stimulation intensity of 10 mA. The magnitude of temporal summation was smaller in dexmedetomidine than in placebo treated dogs at time 10, 30 and 60, but not at time 0. Conclusions During isoflurane anaesthesia, low dose dexmedetomidine suppresses the nociceptive reflex responses after single and repeated electrical stimulation. Clinical relevance This experimental study confirms previous reports on its peri-operative efficacy under clinical conditions, and further indicates that dexmedetomidine might reduce the risk of post-operative chronic pain development.

Cognitive response control in writer's cramp

Disturbances of the motor and sensory system as well as an alteration of the preparation of movements have been reported to play a role in the pathogenesis of dystonias. However, it is unclear whether higher aspects of cortical – like cognitive – functions are also involved. Recently, the NoGo-anteriorization (NGA) elicited with a visual continuous performance test (CPT) during recording of a 21-channel electroencephalogram has been proposed as an electrophysiological standard-index for cognitive response control. The NGA consists of a more anterior location of the positive area of the brain electrical field associated with the inhibition (NoGo-condition) compared with that of the execution (Go-condition) of a prepared motor response in the CPT. This response control paradigm was applied in 16 patients with writer’s cramp (WC) and 14 age matched healthy controls. Topographical analysis of the associated event-related potentials revealed a significant (P < 0.05) NGA effect for both patients and controls. Moreover, patients with WC showed a significantly higher global field power value (P < 0.05) in the Go-condition and a significantly higher difference-amplitude (P < 0.05) in the NoGo-condition. A source location analysis with the low resolution electromagnetic tomography (LORETA) method demonstrated a hypoactivity for the Go-condition in the parietal cortex of the right hemisphere and a hyperactivity in the NoGo-condition in the left parietal cortex in patients with WC compared with healthy controls. These results indicate an altered response control in patients with WC in widespread cortical brain areas and therefore support the hypothesis that the pathogenesis of WC is not restricted to a pure sensory-motor dysfunction.

Phosphate release kinetics in calcareous grassland and forest soils in response to H+ addition

Phosphate release kinetics in soils are of global interest because sustainable plant nutrition with phosphate will be a major concern in the future. Dissolution of phosphate-containing minerals induced by a changing rhizosphere equilibrium through proton input is one important mechanism that releases phosphate into bioavailable forms. Our objectives were (i) to determine phosphate release kinetics during H+ addition in calcareous soils of the Schwäbische Alb, Germany, and to assess the influence of (ii) land-use type (grassland vs. forest) and (iii) management intensity on reactive phosphate pools and phosphate release rate constants during H+ addition. Phosphate release kinetics were characterized by a large fast-reacting phosphatepool, which could be attributed to poorly-crystalline calcium phosphates, and a small slow-reacting phosphate pool probably originating from carbonate-bearing hydroxylapatite. Both reactive phosphate pools—as well as total phosphate concentrations (TP) in soil—were greater in grassland than in forest soils. In organically fertilized grassland soils, concentrations of released phosphate were higher than in unfertilized soils, likely because organic fertilizers contain poorly-crystalline phosphate compounds which are further converted into sparingly soluble phosphate forms. Because of an enriched slow-reacting phosphate pool, mown pastures were characterized by a more continuous slow phosphate release reaction in contrast to clear biphasic phosphate release patterns in meadows. Consequently, managing phosphate release kinetics via management measures is a valuable tool to evaluate longer-term P availability in soil in the context of finite rock phosphate reserves on earth.

Nonviolent factors: Variables associated with ethnic violence, and factors which are associated with nonviolent response to grievances toward members of other ethnic groups

Ethnic violence appears to be the major source of violence in the world. Ethnic hostilities are potentially all-pervasive because most countries in the world are multi-ethnic. Public health's focus on violence documents its increasing role in this issue.^ The present study is based on a secondary analysis of a dataset of responses by 272 individuals from four ethnic groups (Anglo, African, Mexican, and Vietnamese Americans) who answered questions regarding variables related to ethnic violence from a general questionnaire which was distributed to ethnically diverse purposive, nonprobability, self-selected groups of individuals in Houston, Texas, in 1993.^ One goal was psychometric: learning about issues in analysis of datasets with modest numbers, comparison of two approaches to dealing with missing observations not missing at random (conducting analysis on two datasets), transformation analysis of continuous variables for logistic regression, and logistic regression diagnostics.^ Regarding the psychometric goal, it was concluded that measurement model analysis was not possible with a relatively small dataset with nonnormal variables, such as Likert-scaled variables; therefore, exploratory factor analysis was used. The two approaches to dealing with missing values resulted in comparable findings. Transformation analysis suggested that the continuous variables were in the correct scale, and diagnostics that the model fit was adequate.^ The substantive portion of the analysis included the testing of four hypotheses. Hypothesis One proposed that attitudes/efficacy regarding alternative approaches to resolving grievances from the general questionnaire represented underlying factors: nonpunitive social norms and strategies for addressing grievances--using the political system, organizing protests, using the system to punish offenders, and personal mediation. Evidence was found to support all but one factor, nonpunitive social norms.^ Hypothesis Two proposed that the factor variables and the other independent variables--jail, grievance, male, young, and membership in a particular ethnic group--were associated with (non)violence. Jail, grievance, and not using the political system to address grievances were associated with a greater likelihood of intergroup violence.^ No evidence was found to support Hypotheses Three and Four, which proposed that grievance and ethnic group membership would interact with other variables (i.e., age, gender, etc.) to produce variant levels of subgroup (non)violence.^ The generalizability of the results of this study are constrained by the purposive self-selected nature of the sample and small sample size (n = 272).^ Suggestions for future research include incorporating other possible variables or factors predictive of intergroup violence in models of the kind tested here, and the development and evaluation of interventions that promote electoral and nonelectoral political participation as means of reducing interethnic conflict. ^

Electrophysiological indices of response inhibition in a Go/NoGo task predict self-control in a social context.

Recent research demonstrates that response inhibition-a core executive function-may subserve self-regulation and self-control. However, it is unclear whether response inhibition also predicts self-control in the multifaceted, high-level phenomena of social decision-making. Here we examined whether electrophysiological indices of response inhibition would predict self-control in a social context. Electroencephalography was recorded as participants completed a widely used Go/NoGo task (the cued Continuous Performance Test). Participants then interacted with a partner in an economic exchange game that requires self-control. Results demonstrated that greater NoGo-Anteriorization and larger NoGo-P300 peak amplitudes-two established electrophysiological indices of response inhibition-both predicted more self-control in this social game. These findings support continued integration of executive function and self-regulation and help extend prior research into social decision-making processes.

Individual differences in inhibitory control - relationship between baseline activation in lateral PFC and an electrophysiological index of response inhibition

The capacity to inhibit inappropriate responses is crucial for goal-directed behavior. Inhibiting such responses seems to come more easily to some of us than others, however. From where do these individual differences originate? Here, we measured 263 participants' neural baseline activation using resting electroencephalogram. Then, we used this stable neural marker to predict a reliable electrophysiological index of response inhibition capacity in the cued Continuous Performance Test, the NoGo-Anteriorization (NGA). Using a source-localization technique, we found that resting delta, theta, and alpha1 activity in the left middle frontal gyrus and resting alpha1 activity in the right inferior frontal gyrus were negatively correlated with the NGA. As a larger NGA is thought to represent better response inhibition capacity, our findings demonstrate that lower levels of resting slow-wave oscillations in the lateral prefrontal cortex, bilaterally, are associated with a better response inhibition capacity.

Structural Organization of the Corpus Callosum Predicts Attentional Shifts after Continuous Theta Burst Stimulation

Repetitive transcranial magnetic stimulation (rTMS) applied over the right posterior parietal cortex (PPC) in healthy participants has been shown to trigger a significant rightward shift in the spatial allocation of visual attention, temporarily mimicking spatial deficits observed in neglect. In contrast, rTMS applied over the left PPC triggers a weaker or null attentional shift. However, large interindividual differences in responses to rTMS have been reported. Studies measuring changes in brain activation suggest that the effects of rTMS may depend on both interhemispheric and intrahemispheric interactions between cortical loci controlling visual attention. Here, we investigated whether variability in the structural organization of human white matter pathways subserving visual attention, as assessed by diffusion magnetic resonance imaging and tractography, could explain interindividual differences in the effects of rTMS. Most participants showed a rightward shift in the allocation of spatial attention after rTMS over the right intraparietal sulcus (IPS), but the size of this effect varied largely across participants. Conversely, rTMS over the left IPS resulted in strikingly opposed individual responses, with some participants responding with rightward and some with leftward attentional shifts. We demonstrate that microstructural and macrostructural variability within the corpus callosum, consistent with differential effects on cross-hemispheric interactions, predicts both the extent and the direction of the response to rTMS. Together, our findings suggest that the corpus callosum may have a dual inhibitory and excitatory function in maintaining the interhemispheric dynamics that underlie the allocation of spatial attention. SIGNIFICANCE STATEMENT: The posterior parietal cortex (PPC) controls allocation of attention across left versus right visual fields. Damage to this area results in neglect, characterized by a lack of spatial awareness of the side of space contralateral to the brain injury. Transcranial magnetic stimulation over the PPC is used to study cognitive mechanisms of spatial attention and to examine the potential of this technique to treat neglect. However, large individual differences in behavioral responses to stimulation have been reported. We demonstrate that the variability in the structural organization of the corpus callosum accounts for these differences. Our findings suggest novel dual mechanism of the corpus callosum function in spatial attention and have broader implications for the use of stimulation in neglect rehabilitation.

Accuracy of continuous glucose monitoring during differing exercise conditions.

AIM Depending on intensity, exercise may induce a strong hormonal and metabolic response, including acid-base imbalances and changes in microcirculation, potentially interfering with the accuracy of continuous glucose monitoring (CGM). The present study aimed at comparing the accuracy of the Dexcom G4 Platinum (DG4P) CGM during continuous moderate and intermittent high-intensity exercise (IHE) in adults with type 1 diabetes (T1DM). METHODS Ten male individuals with well-controlled T1DM (HbA1c 7.0±0.6% [54±6mmol/mol]) inserted the DG4P sensor 2 days prior to a 90min cycling session (50% VO2peak) either with (IHE) or without (CONT) a 10s all-out sprint every 10min. Venous blood samples for reference glucose measurement were drawn every 10min and euglycemia (target 7mmol/l) was maintained using an oral glucose solution. Additionally, lactate and venous blood gas variables were determined. RESULTS Mean reference blood glucose was 7.6±0.2mmol/l during IHE and 6.7±0.2mmol/l during CONT (p<0.001). IHE resulted in significantly higher levels of lactate (7.3±0.5mmol/l vs. 2.6±0.3mmol/l, p<0.001), while pH values were significantly lower in the IHE group (7.27 vs. 7.38, p=0.001). Mean absolute relative difference (MARD) was 13.3±2.2% for IHE and 13.6±2.8% for CONT suggesting comparable accuracy (p=0.90). Using Clarke Error Grid Analysis, 100% of CGM values during both IHE and CONT were in zones A and B (IHE: 77% and 23%; CONT: 78% and 22%). CONCLUSIONS The present study revealed good and comparable accuracy of the DG4P CGM system during intermittent high intensity and continuous moderate intensity exercise, despite marked differences in metabolic conditions. This corroborates the clinical robustness of CGM under differing exercise conditions. CLINICAL TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT02068638.