Could 13C MRI assist clinical decision-making for patients with heart disease?

Even at this early stage of development, it is clear that the imaging of hyperpolarized (13)C-enriched molecules and their metabolic products offers a new approach to the study of the physiology and disease of the heart. The technology is practical in humans and, for this reason, we consider whether a role in clinical decision-making should motivate further development. The range of interventions available to treat coronary and valvular heart disease is already extensive, and new options are imminent. Yet the appropriate management of patients with left ventricular dysfunction can be challenging because the mechanism of reduced function may be unclear and the ability of the ventricle to respond to therapy may be difficult to predict. Pyruvate is a promising early target for development as a diagnostic agent because it lies at a critical branch point in cardiac biochemistry. The rate of metabolism of hyperpolarized pyruvate to CO(2) relative to lactate may prove to be a useful indicator of preserved mitochondrial function, and therefore provide a specific signal of viable myocardium. Other species including physiological substrates and nonphysiological molecules may provide additional information. Once suitable technology becomes available, it is likely that clinical research will progress quickly. The ability to monitor directly specific metabolic pathways may lead to an improvement in the selection of patients who will benefit from interventions, pharmacologic or otherwise.     

Does psychotherapy homework lead to improvements in depression in cognitive-behavioral therapy or does improvement lead to increased homework compliance?

The bidirectional causal relationships between psychotherapy homework (HW) compliance and changes in depression were assessed in 2 groups of depressed outpatients treated with cognitive-behavioral therapy using nonrecursive structural equation modeling techniques. The data were consistent with the hypothesis that HW compliance had a causal effect on changes in depression, and the magnitude of this effect was large. Patients who did the most HW improved much more than patients who did little or no HW. In contrast, depression severity did not appear to influence HW compliance. HW compliance did not appear to be a proxy for any other, unobserved (3rd) variable, such as motivation. Although the causal effect of HW on depression was large, the correlation between HW and depression was small. Some possible explanations, along with suggestions for future studies, are proposed.     

Automation in clinical bacteriology: what system to choose?

With increased activity and reduced financial and human resources, there is a need for automation in clinical bacteriology. Initial processing of clinical samples includes repetitive and fastidious steps. These tasks are suitable for automation, and several instruments are now available on the market, including the WASP (Copan), Previ‐Isola (BioMerieux), Innova (Becton‐Dickinson) and Inoqula (KIESTRA) systems. These new instruments allow efficient and accurate inoculation of samples, including four main steps: (i) selecting the appropriate Petri dish; (ii) inoculating the sample; (iii) spreading the inoculum on agar plates to obtain, upon incubation, well‐separated bacterial colonies; and (iv) accurate labelling and sorting of each inoculated media. The challenge for clinical bacteriologists is to determine what is the ideal automated system for their own laboratory. Indeed, different solutions will be preferred, according to the number and variety of samples, and to the types of sample that will be processed with the automated system. The final choice is troublesome, because audits proposed by industrials risk being biased towards the solution proposed by their company, and because these automated systems may not be easily tested on site prior to the final decision, owing to the complexity of computer connections between the laboratory information system and the instrument. This article thus summarizes the main parameters that need to be taken into account for choosing the optimal system, and provides some clues to help clinical bacteriologists to make their choice.     

Does contact lead to similarity or similarity to contact?

Evidence from the Finnish Twin Registry (e.g., Rose et al., 1988) shows that adult monozygotic (MZ) twins are more similar, within pairs, in personality if the cotwins are presently cohabiting or in frequent contact than if they are seldom in contact. Results of a follow-up study led Kaprio et al. (1990) to conclude that changes in social contact between monozygotic cotwins precede (and causally contribute to) changes in their intrapair similarity (p. 9). If true, this conclusion has important theoretical implications, e.g., many heritability estimates would have to be revised downward. We adduce evidence suggesting that similarity leads to contact, rather than the other way around. Low correlations between twins' frequency of contact and their absolute within-pair difference on all traits thus far studied indicates that, whichever the direction of causality, the relationship between MZ within-pair similarity and their frequency of contact is very weak.This work was supported in part by Grant 2 RO1 MH37860-06 from the National Institute of Mental Health in support of the Minnesota Twin Registry.Richard Rose, Jaakko Kapno, and Christopher Williams will be replying to this paper in a subsequent issue.     

Can hyper-synchrony in meditation lead to seizures? Similarities in meditative and epileptic brain states

Meditation is used worldwide by millions of people for relaxation and stress relief. Given sufficient practice, meditators may also experience a variety of altered states of consciousness. These states can lead to a variety of unusual experiences, including physical, emotional and psychic disturbances. This paper highlights the correspondences between brain states associated with these experiences and the symptoms and neurophysiology of epileptic simple partial seizures. Seizures, like meditation practice, can result in both positive and negative experiences. The neurophysiology and chemistry underlying simple partial seizures are characterised by a high degree of excitability and high levels of neuronal synchrony in gamma-band brain activity. Following a survey of the literature that shows that meditation practice is also linked to high power gamma activity, an account of how meditation could cause such activity is provided. This paper discusses the diagnostic challenges for the claim that meditation practices lead to brain states similar to those found in epileptic seizures, and seeks to develop our understanding of the range of pathological and non-pathological states that result from a hyper-excited and hyper-synchronous brain.     

Can drug screening lead to candidate therapies for testing in diabetic neuropathy?

A key mechanism of dorsal root ganglia (DRG) neuron injury in high glucose is mitochondrial overload leading to oxidative stress. We screened selected compounds for the ability to prevent hyperglycemia-induced mitochondrial superoxide in primary sensory DRG neurons. Twenty five out of 1,040 compounds decreased both mitochondrial superoxide and subsequent neuronal injury. These data both validate our screening strategy and indicate further mechanistic evaluation of drug hits and related compounds. Such studies may lead to the design of rational therapeutic approaches for this severe complication of diabetes.     

Could ECT be effective in autism?

Autism is increasingly diagnosed, but therapeutic options are limited in many children. ECT is considered as a safe, effective, and life-saving treatment in people of all ages who suffer from affective disorders, acute psychosis, and, in particular, catatonia. There are recent speculations that certain types of autism may be the earliest expression of catatonia and that both disorders have identical risk factors. Therefore, ECT may improve autism and, if started early enough, may prevent further development of autistic symptoms in some children. The use of ECT in autism has never been systematically assessed. There have been two large ECT studies in children in the 1940s. Autism was not assessed in these studies because the autistic syndrome was just then being recognized as a separate entity. Findings from these studies add little to the hypothesis that ECT may be effective in autistic children, but attest to the safety and feasibility of ECT in children. Another limitation is the use of older ECT techniques. What may well be the greatest deterrent to use ECT in autism is widespread anti- ECT sentiment not only among the public but within the medical community as well. All child specialists--psychiatrists, neurologists, psychologists, and developmental pediatricians--should independently review the feasibility, potential, and risk of using ECT in autism. Unless anti-ECT prejudice can be overcome, it is unlikely that any ECT trial in autism is forthcoming. Research areas that may support the hypothesis that ECT is effective in autism should be pursued. First, any link between autism and catatonia should be further explored in clinical and biochemical studies. A GABA theory of autism and catatonia may be pivotal. Second, the role of abnormal GABAA receptor subunit genes in autism and catatonia should be further assessed. Candidate loci for autism and catatonia have been found on the long arm of chromosome 15 where three GABAA receptor subunits genes are located. The GABAA receptor beta 3 subunit gene (GABRB3) was the leading candidate gene for a subgroup of autism in two independent studies. Third, a novel genetic mouse model of autism should be tested. Mutant mice with a targeted deletion of the GABRB3 gene have a complete deficit of the beta 3 subunit of the GABAA receptor. This knockout mouse model seems promising to study developmental effects of altered GABAA receptor function as it relates to certain developmental disorders including autism.     

Written information to patients in clinical genetics: what's the impact?

In all countries of the European Union, oral information must be given to the patient. Written information is generally optional, but physicians are tending more and more to send a copy of the clinical report to the patient. In this study, we aimed to evaluate the impact on patients of sending them written information after a clinical consultation in a French genetics department. During a period of three months, two geneticists and one genetic counselor offered to send each patient a copy of the letter sent to their general practitioners. A questionnaire was sent with this copy. Three hundred and seventy-five patients were seen and 64% of the questionnaires were sent back. Of these, 99% showed that this practice was considered a good idea, and 80% reported that the letter reflected the clinical aspects well. Seventy-two percent thought that receiving this letter improved their understanding of the clinical situation. In general, patients found the words understandable (83%), too medical (20%) or even shocking (3%). Sixty-three percent said that they would have asked their general practitioner to give them the letter. Their main motivation for wanting a copy of this letter was to remember the information in the future, to have the information to pass on to other physicians involved in their health in the future, or to have information concerning the family. Finally, 58% would have preferred a letter sent specifically to them rather than a copy, and suggestions for the contents of such a letter should be further studied.     

Could a deficiency in growth hormone signaling be beneficial to the aging brain?

Several studies have shown that growth hormone (GH)-deficient/resistant animals have a prolonged lifespan compared with their normal siblings. Studies in our laboratory have suggested that both Ames dwarf and GH receptor/GH binding protein knockout (GH-R-KO) mice do not experience age-induced cognitive aging at the same rate as their normal siblings. The studies presented here were aimed at determining whether these long-lived mice experience a delay in age-related changes in behavior. Young and old mice of both strains were tested in an open-field task. In addition, mice of the GH-R-KO strain were tested in the water maze to confirm previous findings using the inhibitory avoidance task that suggested delayed cognitive aging. In each of these studies, normal (wild-type) animals of the same age, sex, and genetic background as the mutants served as controls. Old GH-R-KO mice did not experience the decline in locomotor activity or difference in activity levels in the open-field task seen in the normal animals. Young normal and young and old Ames dwarf mice spent less time in the center of the apparatus compared with old normal animals. There were no signs of age-related changes in emotionality within the GH-R-KO strain. Water maze results also showed that while old normal animals performed poorer than the young normal animals, old GH-R-KO mice did not perform differently from the young normal or young GH-R-KO groups. Taken together, these studies support our previous findings of delayed age-induced cognitive and behavioral decline in GH deficient/resistant mice.     

Could n-gram analysis contribute to genomic island determination?

There are two approaches to identifying genomic and pathogenesis islands (GI/PAIs) in bacterial genomes: the compositional and the functional, based on DNA or protein level composition and gene function, respectively. We applied n-gram analysis in addition to other compositional features, combined them by union and intersection and defined two measures for evaluating the results—recall and precision. Using the best criteria (by training on the Escherichia coli O157:H7 EDL933 genome), we predicted GIs for 14 Enterobacteriaceae family members and for 21 randomly selected bacterial genomes. These predictions were compared with results obtained from HGT DB (based on the compositional approach) and PAI DB (based on the combined approach). The results obtained show that intersecting n-grams with other compositional features improves relative precision by up to 10% in case of HGT DB and up to 60% in case of PAI DB. In addition, it was demonstrated that the union of all compositional features results in maximum recall (up to 37%). Thus, the application of n-gram analysis alongside existing or newly developed methods may improve the prediction of GI/PAIs.