Effects of hypoxia and altered K0 on the membrane potential of rabbit ventricle

The upstroke of the ventricular action potential in the rabbit consits of two depolarizing components with different rates of rise. The effects of hypoxia on the resting potential (RP); the upstroke phases (I and II) and the maximum rate of rise of phase I ( _max) were studied at different external K concentrations (K₀). Perfused hearts were submitted to N₂-equilibrated media containing 1.5 to 10 m K₀. Exposure of oxygenated hearts to different K₀ changed the regenerative response from a fast rising action potential at 1.5 m K₀ to a depressed fast response at 7.5 and 10 m K₀. Hypoxia decreased the action potential amplitude (APA) at all K concentrations. In K₀ ≤ 5 m the reduction of APA was due to a decrease in the amplitude of phase II of the upstroke but the maximum rate of rise ( _max) did not change. In contrast, phase I of the upstroke was markedly depressed by hypoxia in high K₀, but phase II was unmodified and its _max compared well with values reported for other normoxic cardiac cells. Hyperkalemia per se did not slow conduction during normoxia but increased conduction time in hypoxia. The resting potential of hypoxic cells was closer to the K equilibrium potential than in the control. The RP v. K₀/K_i relation suggested that electrogenic Na extrusion persists in hypoxia. The electrogenic fraction of the resting potential as determined from pump inhibition with 10⁻⁴ ouabain amounted to −6 mV. Our results did not indicate whether the differential effects of hypoxia on the upstroke components were potential dependent or were related to direct effects of K⁺ on the ionic currents that determine the action potential. The persistence of phase II during hypoxia in partly depolarized cells may assure the maintenance of propagated electrical activity under conditions that are likely to be encountered in vitro during cardiac ischemia.     

Neonatal hyperglycaemia and abnormal development of the pancreas

Transient and permanent neonatal diabetes mellitus (TNDM and PNDM) are rare conditions occurring in around 1 per 300,000 live births. In TNDM, growth-retarded infants develop diabetes in the first few weeks of life, only to go into remission after a few months with possible relapse to permanent diabetes usually around adolescence or in adulthood. In PNDM, insulin secretory failure occurs in the late fetal or early postnatal period. The very recently elucidated mutations in KCNJ11 and ABCC8 genes, encoding the Kir6.2 and SUR1 subunits of the pancreatic K(ATP) channel involved in regulation of insulin secretion, account for a third to a half of the PNDM cases. Molecular analysis of chromosome 6 anomalies and the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1 provides a tool for distinguishing transient from permanent neonatal diabetes mellitus in the neonatal period. Some patients (those with mutations in KCNJ11 and ABCC8) may be transferred from insulin therapy to sulphonylureas.     

Nicotine decreases DNA methyltransferase 1 expression and glutamic acid decarboxylase 67 promoter methylation in GABAergic interneurons

Tobacco smoking is frequently abused by schizophrenia patients (SZP). The major synaptically active component inhaled from cigarettes is nicotine, hence the smoking habit of SZP may represent an attempt to use nicotine self-medication to correct (i) a central nervous system nicotinic acetylcholine receptor (nAChR) dysfunction, (ii) DNA-methyltransferase 1 (DMT1) overexpression in GABAergic neurons, and (iii) the down-regulation of reelin and GAD(67) expression caused by the increase of DNMT1-mediated hypermethylation of promoters in GABAergic interneurons of the telencephalon. Nicotine (4.5-22 micromol/kg s.c., 4 injections during the 12-h light cycle for 4 days) decreases DNMT1 mRNA and protein and increases GAD(67) expression in the mouse frontal cortex (FC). This nicotine-induced decrease of DNMT1 mRNA expression is greater (80%) in laser microdissected FC layer I GABAergic neurons than in the whole FC (40%), suggesting selectivity differences for the specific nicotinic receptor populations expressed in GABAergic neurons of different cortical layers. The down-regulation of DNMT1 expression induced by nicotine in the FC is also observed in the hippocampus but not in striatal GABAergic neurons. Furthermore, these data show that in the FC, the same doses of nicotine that decrease DNMT1 expression also (i) diminished the level of cytosine-5-methylation in the GAD(67) promoter and (ii) prevented the methionine-induced hypermethylation of the same promoter. Pretreatment with mecamylamine (6 micromol/kg s.c.), an nAChR blocker that penetrates the blood-brain barrier, prevents the nicotine-induced decrease of FC DNMT1 expression. Taken together, these results suggest that nicotine, by activating nAChRs located on cortical or hippocampal GABAergic interneurons, can up-regulate GAD(67) expression via an epigenetic mechanism. Nicotine is not effective in striatal medium spiny GABAergic neurons that primarily express muscarinic receptors.     

There and up again: On the uses and misuses of neuroimaging in psychology

The aim of this article is to discuss the conditions under which functional neuroimaging can contribute to the study of higher cognition. We begin by presenting two case studies—on moral and economic decision making—which will help us identify and examine one of the main ways in which neuroimaging can help advance the study of higher cognition. We agree with critics that functional magnetic resonance imaging (fMRI) studies seldom “refine” or “confirm” particular psychological hypotheses, or even provide details of the neural implementation of cognitive functions. However, we suggest that neuroimaging can support psychology in a different way—namely, by selecting among competing hypotheses of the cognitive mechanisms underlying some mental function. One of the main ways in which neuroimaging can be used for hypothesis selection is via reverse inferences, which we here examine in detail. Despite frequent claims to the contrary, we argue that successful reverse inferences do not assume any strong or objectionable form of reductionism or functional locationism. Moreover, our discussion illustrates that reverse inferences can be successful at early stages of psychological theorizing, when models of the cognitive mechanisms are only partially developed.     

From Bedside Back to Bench? A Commentary on: “The Future of Cognitive Behavioral Therapy for Insomnia: What Important Research Remains to Be Done?”

In this month's issue of the Journal of Clinical Psychology, Vitiello and colleagues articulate an important research agenda that will help advance cognitive‐behavioral therapy for insomnia (CBT‐I) research and clinical practice. In addition to this ambitious agenda, we also propose that pursuing a parallel research program, focusing on treatment mechanisms and process will help move the CBT‐I field forward and optimize therapeutic dissemination and uptake.     

Mechanism-based Classification and Physical Therapy Management of Persons with Cancer Pain: A Prospective Case Series

Context:

Mechanism-based classification (MBC) was established with current evidence and physical therapy (PT) management methods for both cancer and for noncancer pain.

Aims:

This study aims to describe the efficacy of MBC-based PT in persons with primary complaints of cancer pain.

Settings and Design:

A prospective case series of patients who attended the physiotherapy department of a multispecialty university-affiliated teaching hospital.

Material and Methods:

A total of 24 adults (18 female, 6 male) aged 47.5 ± 10.6 years, with primary diagnosis of heterogeneous group of cancer, chief complaints of chronic disabling pain were included in the study on their consent for participation The patients were evaluated and classified on the basis of five predominant mechanisms for pain. Physical therapy interventions were recommended based on mechanisms identified and home program was prescribed with a patient log to ensure compliance. Treatments were given in five consecutive weekly sessions for five weeks each of 30 min duration.

Statistical Analysis Used:

Pre–post comparisons for pain severity (PS) and pain interference (PI) subscales of Brief pain inventory-Cancer pain (BPI-CP) and, European organization for research and treatment in cancer-quality of life questionnaire (EORTC-QLQ-C30) were done using Wilcoxon signed-rank test at 95% confidence interval using SPSS for Windows version 16.0 (SPSS Inc, Chicago, IL).

Results:

There were statistically significant (P < 0.05) reduction in pain severity, pain interference and total BPI-CP scores, and the EORTC-QLQ-C30.

Conclusion:

MBC-PT was effective for improving BPI-CP and EORTC-QLQ-C30 scores in people with cancer pain.     

高频震荡通气技术研究现状分析与展望

以低平均气道压和小潮气量为主要特征的高频震荡通气(HFOV),自出现以来备受医务、科研人员的关注。本文就HFOV通气技术方面的研究现状与发展趋势进行了分析和展望,重点介绍与分析了有关HFOV的通气模型、通气机制和通气模式方面的研究现状。并藉此提出,在未来一段时期内,对HFOV通气技术的研究将主要集中在三个方面:建立多级、高阶、非线性的黏性阻力、惯性阻力和顺应性(RIC)通气模型;更为充分地揭示HFOV之所以能够有效通气的机制;研究实现低风险的无创HFOV。对HFOV通气技术的研究与发展,将为呼吸系统疾病患者提供一种不同于常频通气的通气方式。     

Action‐Monitoring Alterations as Indicators of Predictive Deficits in Schizophrenia

A flexible and dynamically adjustable behavior is crucial to adapt to a continuously changing environment. In order to optimally adapt, we need to learn from the consequences of our behavior. We usually learn through different kinds of prediction errors, which occur when we experience unexpected situations due to false predictions. With this literature review, we intended to contribute to current etiological models that ascribe various positive symptoms (particularly delusions and hallucinations) in patients with schizophrenia to false prediction errors and deficient predictive learning. We discuss alterations in the electrophysiological measure of the error‐related negativity/error negativity (ERN/Ne) as a global deficit and a trait in schizophrenia, as they have been observed in different samples of patients with schizophrenia, in individuals at high‐risk and individuals with subclinical schizotypal traits. As the ERN/Ne can itself be considered the result of predictive processes (evaluation of current action outcomes as worse than expected), we propose that the reported alterations indicate that patients suffering from schizophrenic illnesses fail to adequately classify the outcomes of their actions as better or worse than expected due to a deficit in self‐monitoring. Furthermore, we discuss results in further action‐monitoring components, such as the correct response negativity (CRN)—a smaller negativity elicited by correct responses; and error positivity (Pe)—a later positivity assumed to reflect conscious error processing. The reported results show normal Pe amplitudes and normal post‐error adjustments (adaptations after committed error to improve performance), indicating an intact later and conscious processing. From the results of diminished differences between ERN/Ne and CRN amplitudes, we conclude a general predictive deficit in early aspects of self‐monitoring associated with positive symptoms in patients with schizophrenia.