Predicting Adaptive Behavior in the Environment from Central Nervous System Dynamics

To generate adaptive behavior, the nervous system is coupled to the environment. The coupling constrains the dynamical properties that the nervous system and the environment must have relative to each other if adaptive behavior is to be produced. In previous computational studies, such constraints have been used to evolve controllers or artificial agents to perform a behavioral task in a given environment. Often, however, we already know the controller, the real nervous system, and its dynamics. Here we propose that the constraints can also be used to solve the inverse problem—to predict from the dynamics of the nervous system the environment to which they are adapted, and so reconstruct the production of the adaptive behavior by the entire coupled system. We illustrate how this can be done in the feeding system of the sea slug Aplysia. At the core of this system is a central pattern generator (CPG) that, with dynamics on both fast and slow time scales, integrates incoming sensory stimuli to produce ingestive and egestive motor programs. We run models embodying these CPG dynamics—in effect, autonomous Aplysia agents—in various feeding environments and analyze the performance of the entire system in a realistic feeding task. We find that the dynamics of the system are tuned for optimal performance in a narrow range of environments that correspond well to those that Aplysia encounter in the wild. In these environments, the slow CPG dynamics implement efficient ingestion of edible seaweed strips with minimal sensory information about them. The fast dynamics then implement a switch to a different behavioral mode in which the system ignores the sensory information completely and follows an internal “goal,” emergent from the dynamics, to egest again a strip that proves to be inedible. Key predictions of this reconstruction are confirmed in real feeding animals.     

Protein C zymogen in severe sepsis: a double-blinded,placebo-controlled,randomized study

Purpose

To determine whether protein C zymogen (protein C concentrates or human protein C) improves clinically relevant outcomes in adult patients with severe sepsis and septic shock.

Methods

This is a randomized, double-blind, placebo-controlled, parallel-group trial that from September 2012 to June 2014 enrolled adult patients with severe sepsis or septic shock and high risk of death and of bleeding (e.g., APACHE II greater than 25, extracorporeal membrane oxygenation or disseminated intravascular coagulopathy). All patients completed their follow-up 90 days after randomization and data were analyzed according to the intention-to-treat principle. Follow-up was performed at 30 and 90 days after randomization. The primary endpoint was a composite outcome of prolonged intensive care unit (ICU) stay and/or 30-day mortality. Secondary endpoints included mortality.

Results

The study was stopped early in a situation of futility for the composite outcome of prolonged ICU stay and/or 30-day mortality that was 79 % (15 patients) in the protein C zymogen group and 67 % (12 patients) in the placebo group (p = 0.40) and for a concomitant safety issue: ICU mortality was 79 % (15 patients) in the protein C zymogen group vs 39 % (7 patients) in the placebo group (p = 0.020), and 30-day mortality was 68 vs 39 % (p = 0.072).

Conclusion

Protein C zymogen did not improve clinically relevant outcomes in severe sepsis and septic shock adult patients. Given its high cost and the potential increase in mortality, the use of this drug in adult patients should be discouraged.

     

Giving birth: the voices of Russian women

PURPOSE: To gain an understanding of the meaning of childbirth to women living in St. Petersburg, the Russian Federation. STUDY DESIGN AND METHOD: Twenty-four Russian women who had given birth in the past 6 months participated in this phenomenological study and were interviewed and audio-taped about the meaning of childbirth. Data collection and analysis occurred concurrently. RESULTS: The Russian sociocultural context of childbirth was identified in specific themes: (1) adhering to cultural traditions, (2) accessing information, (3) maintaining a healthy lifestyle, (4) articulating the spiritual and emotional meaning of giving birth, and (5) transforming as a mother and a person. Study participants reported reading extensively during pregnancy as well as accessing Web-based information about childbirth. Women chose to give their newborns traditional Slavic names and have their infants christened. CLINICAL IMPLICATIONS: The findings of qualitative studies can be used to guide clinical practice, because they provide rich data about essential life events and reactions associated with them. Women from Russia are emigrating to countries all over the world, and thus, their cultural views of childbirth are essential knowledge for the provision of appropriate nursing care. With dramatic socioeconomic and political changes occurring over the past 15 years, along with major changes in healthcare delivery systems, listening to the voices of Russian childbearing women giving birth is vital information for nurses working in maternal-child health settings.     

Atorvastatin lowers portal pressure in cirrhotic rats by inhibition of RhoA/Rho-kinase and activation of endothelial nitric oxide synthase

In cirrhosis, increased RhoA/Rho-kinase signaling and decreased nitric oxide (NO) availability contribute to increased intrahepatic resistance and portal hypertension. Hepatic stellate cells (HSCs) regulate intrahepatic resistance. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) inhibit synthesis of isoprenoids, which are necessary for membrane translocation and activation of small GTPases like RhoA and Ras. Activated RhoA leads to Rho-kinase activation and NO synthase inhibition. We therefore investigated the effects of atorvastatin in cirrhotic rats and isolated HSCs. Rats with secondary biliary cirrhosis (bile duct ligation, BDL) were treated with atorvastatin (15 mg/kg per day for 7 days) or remained untreated. Hemodynamic parameters were determined in vivo (colored microspheres). Intrahepatic resistance was investigated in in situ perfused livers. Expression and phosphorylation of proteins were analyzed by RT-PCR and immunoblots. Three-dimensional stress-relaxed collagen lattice contractions of HSCs were performed after incubation with atorvastatin. Atorvastatin reduced portal pressure without affecting mean arterial pressure in vivo. This was associated with a reduction in intrahepatic resistance and reduced responsiveness of in situ-perfused cirrhotic livers to methoxamine. Furthermore, atorvastatin reduced the contraction of activated HSCs in a 3-dimensional stress-relaxed collagen lattice. In cirrhotic livers, atorvastatin significantly decreased Rho-kinase activity (moesin phosphorylation) without affecting expression of RhoA, Rho-kinase and Ras. In activated HSCs, atorvastatin inhibited the membrane association of RhoA and Ras. Furthermore, in BDL rats, atorvastatin significantly increased hepatic endothelial nitric oxide synthase (eNOS) mRNA and protein levels, phospho-eNOS, nitrite/nitrate, and the activity of the NO effector protein kinase G (PKG). CONCLUSION: In cirrhotic rats, atorvastatin inhibits hepatic RhoA/Rho-kinase signaling and activates the NO/PKG-pathway. This lowers intrahepatic resistance, resulting in decreased portal pressure. Statins might represent a therapeutic option for portal hypertension in cirrhosis.     

Asymmetric cerebral embolic load and postoperative cognitive dysfunction in cardiac surgery

BACKGROUND: The aim of the study was to determine the effects of asymmetric cerebral embolic load on cognitive functions. METHODS: Thirty-six open heart surgery (OH) and 26 coronary artery bypass grafting (CABG) patients were evaluated by neuropsychological and transcranial Doppler tests. RESULTS: OH was associated with a significantly larger microembolic load in comparison to CABG. In OH patients, the microembolic load at the left middle cerebral artery correlated with a verbal memory decline, whereas the microembolic load at the right middle cerebral artery correlated with a nonverbal memory deficit. CABG patients also showed a postoperative verbal memory decline which correlated with cardiopulmonary bypass length but not with microembolic load. CONCLUSION: Massive microembolic load during OH induces specific cognitive impairment in accordance to the brain region to which they are delivered. In atherosclerotic patients, the left temporal region is especially prone to perioperative ischemia.     

The Impact of Element–Element Interactions on Antioxidant Enzymatic Activity in the Blood of White Stork (Ciconia ciconia) Chicks

The aim of this work was to determine interrelationships among macroelements Na, K, Ca, Mg, and Fe, microelements Zn, Cu, Mn, and Co, and toxic heavy metals Pb and Cd in the blood of white stork Ciconia ciconia, during postnatal development, in different Polish environments, and their impact on the activity of antioxidant enzymes. We considered the content of thiobarbituric acid-reactive substances (TBARSs), i.e., malondialdehyde (MDA), and activity of superoxide dismutase (SOD), catalase (CAT), ceruloplasmine (CP), glutathione peroxidase (GPx), and glutathione reductase (GR). Blood samples were collected from storks developing at Odra meadows (Kłopot; southwestern Poland). They were compared with blood of chicks from several suburban sites located 20 km away from Zielona Góra (0.1 million inhabitants; southwestern Poland) and near Głogów, where a copper smelter is situated. We also conducted research in the Pomeranian region (Cecenowo; northern Poland). We collected blood samples via venipuncture of the brachial vein of chicks in 2005–2007. They were retrieved from the nest and placed in individual ventilated cotton sacks. The blood was collected using a 5-ml syringe washed with ethylenediaminetetraacetic acid (EDTA). We found significant interactions between macro- and microelements and enzymatic activity and TBARS products. We noticed the predominance of Cd and Pb participation in element–enzyme interactions. Simultaneously, we found interrelationships between cadmium and Na, K, Ca, Mg, and Fe and the activity of antioxidant enzymes SOD, CAT, CP, GR, and TBARS products in the blood of white stork chicks. In the case of lead these relationships were not numerous and they were significant for Ca, Mg, Cu, Mn, and Co. Correlations with enzymes were significant for Pb-CAT and Pb-TBARS. We noted that activities of most enzymes (SOD, CAT, CP, GR) and TBARS products are determined by their interactions with physiological elements Na, Ca, Mg, Fe, and Zn and toxic heavy metals. White stork chicks ranged in age from 17 to 59 days. Concentrations of elements in the blood were age related. Among enzymes, only SOD, CAT, and GPx were age related. Young storks differed in the case of element concentration (except for Ca, Zn, and Cd) and enzymatic activity. We found that significant element–element interaction/enzyme activity predominated in the case of physiological elements and toxic metals, which we explain by the intensive and prevailing access of toxic metals in redox reactions. This causes changes in the priority of these metals, reflected by their influence on the enzymatic activity of antioxidant enzymes. The content of Cd and Pb in blood of young storks from different regions tends to affect the lipid peroxidation process negatively. However, in many cases we observed an increase in enzymatic activity with an increase in heavy metals. This indicates the changes in oxidative stress intensity in chicks in response to environmental differentiation. The increase in lipoperoxidation modifies antioxidant enzyme activity and causes changes in SOD, CAT, CP, GPx, and GR activity in chicks from various regions, principally increases in enzyme activity in chicks from polluted environments and suburbs. We suggest that the source of heavy metals in chicks’ blood might be used as a biological test system of adaptation to oxidative stress. We also report that a high level of heavy metals is accompanied by increased lipid peroxidation. Thus young storks are probably significantly susceptible to environmental conditions. They demonstrated initiation of lipoperoxidation and oxidative modification of proteins that coincide with chemical elements, as a possible antioxidant defense system.