Association Between Patient and Physician Sex and Physician-Estimated Stroke and Bleeding Risks in Atrial Fibrillation

Background

Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.

Episodic memory bias and the symptoms of schizophrenia.

Much of the research on episodic memory in schizophrenia spectrum disorders has focused on memory deficits and how they relate to clinical measures such as outcome. Memory bias refers to the modulatory influence that state or trait psychopathology may exert on memory performance for specific categories of stimuli, often emotional in nature. For example, subjects suffering from depression frequently have better memory for negative stimuli than for neutral or positive ones. This dimension of memory function has received only scant attention in schizophrenia research but could provide fresh new insights into the relation between symptoms and neurocognition. This paper reviews the studies that have explored memory biases in individuals with schizophrenia. With respect to positive symptoms, we examine studies that have explored the link between persecutory delusions and memory bias for threatening information and between psychosis and a memory bias toward external source memory. Although relatively few studies have examined negative symptoms, we also review preliminary evidence indicating that flat affect and anhedonia may lead to some specific emotional memory biases. Finally, we present recent findings from our group delineating the relation between emotional valence for faces and memory bias toward novelty and familiarity, both in schizophrenia patients and in healthy control subjects. A better understanding of the biasing effects of psychopathology on memory in schizophrenia (but also on other cognitive functions, such as attention, attribution, and so forth) may provide a stronger association between positive and negative symptoms and memory function. Memory measures sensitive to such biases may turn out to be stronger predictors of clinical and functional outcome.     

Immunomodulatory Activity of A Novel Nucleoside, 7-thia-8-oxoguanosine: I. Activation of Natural Killer Cells in Mice

We reported recently that a novel immunomodulator, 7-thia-8-oxoguanosine (7T80G)² inhibited formation of pulmonary melanoma metastases (1), prevented against viral infection in mice (2) and potentiated the efficacy of a weakly immunogenic leukemia vaccine (3). Since certain tumor metastases and virus infected cells are targets to natural killer cells (NK cells), we now investigated whether 7T80G is capable of activating NK cells in mice using NK cell sensitive YAC-1 and B16 and NK cell insensitive P815 targets. CBA/CaJ spleen cells incubated in vitro with 7T80G at concentrations ranging from 0.005 to 0.5 mM responded with increased NK cell activity (32-62 %) compared to controls (4-8%) to YAC-1 targets. Similar levels of augmentation in NK cell activity were observed when 40-168 mg/kg of 7T80G was administered in vivo. In addition to the spleen, 7T80G activated NK cells in the bone marrow (BM), the lungs, the liver, and in peritoneal exudate cells (PE). Although 7T80G elicited activation of NK cells was observed as early as three hours after treatment, the maximal activity was observed after 24 h in the spleen; 12 h in the BM; 48 h in the lungs, and 72 h in PE. Administration of the drug by s.c, i.v., and i.p. routes all induced activition of NK cells in spleen, BM and PE. 7T80G was found to activate NK cells in seven inbred and an outbred mouse strain, suggesting that the induced cytotoxicity against allogeneic and syngeneic tumor cells is not strain specific as well as independent of MHC restriction. C3H/He, CBA/CaJ and BDF/1 displayed higher levels of increased NK cell activity, whereas AKR mice were low responders. Low concentrations of IL-2 (0.25-5 U/ml) that induce little or no NK cell activity, when used in combination with 7T80G, elicited significant enhancement of NK cell cytotoxicity. In contrast, IFN and 7T80G showed no such synergism.     

Human balancing of an inverted pendulum: position control by small, ballistic-like, throw and catch movements

In standing, there are small sways of the body. Our interest is to use an artificial task to illuminate the mechanisms underlying the sways and to account for changes in their size. Using the ankle musculature, subjects balanced a large inverted pendulum. The equilibrium of the pendulum is unstable and quasi-regular sway was observed like that in quiet standing. By giving full attention to minimising sway subjects could systematically reduce pendulum movement. The pendulum position, the torque generated at each ankle and the soleus and tibialis anterior EMGs were recorded. Explanations about how the human inverted pendulum is balanced usually ignore the fact that balance is maintained over a range of angles and not just at one angle. Any resting equilibrium position of the pendulum is unstable and in practice temporary; movement to a different resting equilibrium position can only be accomplished by a biphasic 'throw and catch' pattern of torque and not by an elastic mechanism. Results showed that balance was achieved by the constant repetition of a neurally generated ballistic-like biphasic pattern of torque which can control both position and sway size. A decomposition technique revealed that there was a substantial contribution to changes in torque from intrinsic mechanical ankle stiffness; however, by itself this was insufficient to maintain balance or to control position. Minimisation of sway size was caused by improvement in the accuracy of the anticipatory torque impulses. We hypothesise that examination of centre of mass and centre of pressure data for quiet standing will duplicate these results.     

Regulatory properties of brain glutamate decarboxylase (GAD): the apoenzyme of GAD is present principally as the smaller of two molecular forms of GAD in brain

The apoenzyme of glutamate decarboxylase [enzyme without bound cofactor, pyridoxal 5'-phosphate (pyridoxal-P)] serves as a reservoir of inactive glutamate decarboxylase (GAD) that can be activated when additional GABA synthesis is required. We have investigated which of two molecular forms of GAD is present as apoenzyme in synaptosomes and in cortex, caudate nucleus, hippocampus, and cerebellum of rat brain. Endogenous glutamate apodecarboxylase (apoGAD) was labeled by incubating extracts of synaptosomes or punches of each region with 32P-pyridoxal-P, followed by reduction with NaBH4, to link covalently the 32P-pyridoxal-P to GAD. Proteins were separated by SDS-PAGE. Punches from all four brain regions and forebrain synaptosomes contained two forms of GAD with apparent Mrs of 63 and 65 kDa as identified by immunoblotting with four antiGAD sera. Punches and synaptosomes contained a major 32P-pyridoxal-P-labeled band with an apparent Mr of 63 kDa that was stained on immunoblots by the antiGAD serum 1440 and the monoclonal antibody GAD-6, and a minor labeled band at 65 kDa that was stained by the 1440, 6799, and K2 antisera. Synaptosomes contained remarkably few other strongly labeled proteins, but punches contained several other labeled bands. Three additional lines of evidence indicate that the labeled 63-kDa protein is apoGAD: (1) it was purified by immunoaffinity chromatography with the GAD-1 monoclonal antibody; (2) it yielded one major labeled peptide when digested with chymotrypsin, and that peptide appeared identical in peptide-mapping experiments to the labeled active-site peptide isolated from chromatographically prepared rat brain GAD; and (3) its labeling was selectively blocked by 4-deoxypyridoxine 5'-phosphate, a competitive inhibitor of the binding of pyridoxal-P to GAD.(ABSTRACT TRUNCATED AT 250 WORDS)