General anesthesia (GA) is a reversible drug-induced state of altered arousal required for more than 60,000 surgical procedures each day in the United States alone. Sedation and unconsciousness under GA are associated with stereotyped electrophysiological oscillations that are thought to reflect profound disruptions of activity in neuronal circuits that mediate awareness and cognition. Computational models make specific predictions about the role of the cortex and thalamus in these oscillations. In this paper, we provide in vivo evidence in rats that alpha oscillations (10-15 Hz) induced by the commonly used anesthetic drug propofol are synchronized between the thalamus and the medial prefrontal cortex. We also show that at deep levels of unconsciousness where movement ceases, coherent thalamocortical delta oscillations (1-5 Hz) develop, distinct from concurrent slow oscillations (0.1-1 Hz). The structure of these oscillations in both cortex and thalamus closely parallel those observed in the human electroencephalogram during propofol-induced unconsciousness. During emergence from GA, this synchronized activity dissipates in a sequence different from that observed during loss of consciousness. A possible explanation is that recovery from anesthesiainduced unconsciousness follows a "boot-up" sequence actively driven by ascending arousal centers. The involvement of medial prefrontal cortex suggests that when these oscillations (alpha, delta, slow) are observed in humans, self-awareness and internal consciousness would be impaired if not abolished. These studies advance our understanding of anesthesia-induced unconsciousness and altered arousal and further establish principled neurophysiological markers of these states.anesthesia | prefrontal cortex | thalamus | coherence | propofol G eneral anesthesia (GA) is a reversible drug-induced state consisting of unconsciousness, analgesia, amnesia, akinesia, and physiological stability (1). In the United States nearly 60,000 surgical procedures are conducted under GA every day, making GA one of the most common manipulations of the brain and central nervous system in medicine (1). The molecular mechanisms by which anesthetic drugs alter brain function have been well characterized (2, 3). Detailed analyses of neural circuitand systems-level mechanisms of GA are more recent (1, 4, 5). Understanding the system-wide effects of anesthetic drugs is necessary in order to understand how these drugs produce states of altered arousal and unconsciousness.One of the most commonly used anesthetic drugs is 2,6-diisopropylphenol (propofol), a GABA-A receptor agonist (6). Electroencephalogram (EEG) recordings in humans during gradual induction of unconsciousness with propofol show the appearance of frontal β oscillations (15-30 Hz) at the onset of sedation, followed by the appearance of coherent frontal α (8-12 Hz) oscillations (7-10) and widespread slow (0.1-1 Hz) and δ (1-4 Hz) oscillations (7, 11, 12) when subjects no longer respond to sensory stimuli. Biophysical models of neuronal dy...

In obesity, dysregulation of adipocytokines is involved in several pathological conditions including diabetes and certain cancers. As a member of the adipocytokines, adiponectin plays crucial roles in whole-body energy homeostasis. Recently, it has been reported that the level of plasma adiponectin is reduced in several types of cancer patients. However, it is largely unknown whether and how adiponectin affects colon cancer cell growth. Here, we show that adiponectin suppresses the proliferation of colon cancer cells including HCT116, HT29, and LoVo. In colon cancer cells, adiponectin attenuated cell cycle progression at the G(1)/S boundary and concurrently increased expression of cyclin-dependent kinase inhibitors such as p21 and p27. Adiponectin stimulated AMP-activated protein kinase (AMPK) phosphorylation whereas inhibition of AMPK activity blunted the effect of adiponectin on the proliferation of colon cancer cells. Furthermore, knockdown of adiponectin receptors such as AdipoR1 and AdipoR2 relieved the suppressive effect of adiponectin on the growth of colon cancer cells. In addition, adiponectin repressed the expression of sterol regulatory element binding protein-1c, which is a key lipogenic transcription factor associated with colon cancers. These results suggest that adiponectin could inhibit the growth of colon cancer cells through stimulating AMPK activity.

Electroencephalogram (EEG) approaches may provide important information about developmental changes in brain-state dynamics during general anesthesia. We used multi-electrode EEG, analyzed with multitaper spectral methods and video recording of body movement to characterize the spatio-temporal dynamics of brain activity in 36 infants 0–6 months old when awake, and during maintenance of and emergence from sevoflurane general anesthesia. During maintenance: (1) slow-delta oscillations were present in all ages; (2) theta and alpha oscillations emerged around 4 months; (3) unlike adults, all infants lacked frontal alpha predominance and coherence. Alpha power was greatest during maintenance, compared to awake and emergence in infants at 4–6 months. During emergence, theta and alpha power decreased with decreasing sevoflurane concentration in infants at 4–6 months. These EEG dynamic differences are likely due to developmental factors including regional differences in synaptogenesis, glucose metabolism, and myelination across the cortex. We demonstrate the need to apply age-adjusted analytic approaches to develop neurophysiologic-based strategies for pediatric anesthetic state monitoring.DOI: http://dx.doi.org/10.7554/eLife.06513.001

Background/Aims We investigated gut flora characteristics in patients with functional constipation (FC) and influences of short-term treatment with VSL#3 probiotic on flora and symptom improvement. Methods Thirty patients fulfilling Rome III criteria for FC and 30 controls were enrolled. Fecal samples were obtained before and after VSL#3 intake (one sachet twice daily for 2 weeks) and flora were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Symptom changes were also investigated. Results The fold differences in Bifidobacterium and Bacteroides species were significantly lower in feces from FC, compared to in controls ( P = 0.030 and P = 0.021). After taking VSL#3, the fold differences in Lactobacillus , Bifidobacterium and Bacteroides species increased in controls ( P = 0.022, P = 0.018, and P = 0.076), but not in FC. Mean Bristol scores and complete spontaneous bowel movements (CSBMs)/week increased significantly in FC after ingesting VSL#3 (both P < 0.001). Relief of subjective CSBM frequency, stool consistency and abdominal bloating were reported in 70%, 60%, and 47% of patients. After VSL#3 cessation, 44.4% of patients with symptom improvement experienced constipation recurrence mostly within one month. Conclusions Bifidobacterium and Bacteroides species might be quantitatively altered in FC. A short-term VSL#3 treatment can improve clinical symptoms of FC. Further studies are needed to investigate VSL#3’s additional effects beyond altering gut flora to allevate constipation.