Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium.

The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.

Why multilayer graphene on 4H-SiC(0001[over ]) behaves like a single sheet of graphene.

We show experimentally that multilayer graphene grown on the carbon terminated SiC(0001[over ]) surface contains rotational stacking faults related to the epitaxial condition at the graphene-SiC interface. Via first-principles calculation, we demonstrate that such faults produce an electronic structure indistinguishable from an isolated single graphene sheet in the vicinity of the Dirac point. This explains prior experimental results that showed single-layer electronic properties, even for epitaxial graphene films tens of layers thick.

Electronic structure of epitaxial graphene layers on SiC: effect of the substrate.

A strong substrate-graphite bond is found in the first all-carbon layer by density functional theory calculations and x-ray diffraction for few graphene layers grown epitaxially on SiC. This first layer is devoid of graphene electronic properties and acts as a buffer layer. The graphene nature of the film is recovered by the second carbon layer grown on both the (0001) and (0001[over]) 4H-SiC surfaces. We also present evidence of a charge transfer that depends on the interface geometry. Hence the graphene is doped and a gap opens at the Dirac point after three Bernal stacked carbon layers are formed.

The effect of ovary implants on juvenile hormone production by corpora allata of male Diploptera punctata.

In the cockroach Diploptera punctata, vitellogenic basal oocytes stimulate juvenile hormone production by the corpora allata. Experiments with males were designed to determine whether oocytes must grow vitellogenically in order to stimulate juvenile hormone production. Two ovarioles with vitellogenic basal oocytes were implanted into unoperated and sham-operated males that do not produce vitellogenin, and males with denervated corpora allata, that produce more juvenile hormone, and sometimes more vitellogenin. Males with corpora allata in similar conditions were injected with saline as controls. In males with denervated corpora allata compared to sham-operated and unoperated males, the implanted basal oocytes showed a greater increase in length, protein, and vitellin content. Juvenile hormone synthesis by denervated corpora allata in males with ovariole implants was greater than in controls. In 10 of 50 males with denervated corpora allata in which one or no ovarioles grew, juvenile hormone production was not higher than in controls. This suggests that if sufficient juvenile hormone is not present to produce vitellogenin, or oocytes do not take vitellogenin up, juvenile hormone production is not stimulated. In sham-operated males implanted with ovarioles, no difference was detected in juvenile hormone synthesis compared to controls. However when unoperated males were used a significant increase was detected. This suggests that intact nerves from the brain to the corpora allata restrained juvenile hormone production so that ovarioles could elicit only slight stimulation of the corpora allata, and oocytes continued vitellogenesis but more slowly than in denervated males. Thus the extent of vitellogenesis appears to determine the ability of ovaries to stimulate juvenile hormone production.

A mixture of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and non-ortho polychlorinated biphenyls (PCBs) changed the lipid content of pregnant Long Evans rats.

Pregnant Long Evans rats received 1.0 microg/kg of dioxin toxic equivalents (TEQ) by oral gavage on the 15th gestational day (GD 15), using a dosing mixture that contained two polychlorinated dioxins, four polychlorinated furans and three non-ortho polychlorinated biphenyls (PCBs). Rats were sacrificed on GD 16, GD 21 and postnatal day 4 (PND 4). The lipid content of fetus, pup, placenta and maternal liver, serum and adipose tissue were determined. Treated GD 16 and GD 21 fetuses had identical lipid content to the control group, yet the lipid content of treated pups on PND 4 was 32% higher than that of the control group. On the other hand, the lipid content of placenta, liver, and serum from the treated dams was 44-50%, 24%, and 38% lower than that of the control group, respectively. Thus, a low-dose mixture of dioxin-like compounds can cause changes in lipid content. The lipid content of offspring was not affected until they were exposed via lactation.

Disposition of polychlorinated dibenzo-p-dioxins, dibenzofurans, and non-ortho polychlorinated biphenyls in pregnant long evans rats and the transfer to offspring.

Pharmacokinetic properties of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDFs), and non-ortho biphenyls (PCBs) play a critical role in their relative toxicity. The present study examined the transfer of these chemicals to offspring and placenta. Pregnant Long Evans rats received 0.0 (control), 0.05, 0.2, 0.8, and 1.0 microg/kg of dioxin toxic equivalence (TEQ) by oral gavage on the 15th gestational day (GD 15), using a dosing mixture that contained 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 1,2,3,7,8-pentachlorodibenzofuran (1-PeCDF), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), octachlorodibenzofuran (OCDF), 3,3',4,4'-tetrachlorobiphenyl (PCB 77), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), and 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) in ratios approximating that in food. Rats were euthanized on GD 16, GD 21, and postnatal day 4 (PND 4). The chemical concentrations in fetus, pup, placenta, and maternal liver, serum, and adipose tissue were determined using gas chromatography/high-resolution mass spectrometry. A dose-dependent increase in hepatic sequestration was seen with TCDD, PeCDD, 4-PeCDF, OCDF, PCB 126, and PCB 169, and the transfer to offspring was reduced at higher doses. 4-PeCDF, PeCDD and PCB 126 showed higher liver affinity than TCDD. TCDF, 1-PeCDF, and PCB 77 were metabolized rapidly. On GD 16, TCDD and the three PCBs reached equilibration between the fetus and placenta, but this did not occur with PeCDD and 4-PeCDF until GD 21, according to the lipid-based concentrations. Offspring compartments received more of the dosed compounds lactationally than transplacentally (7-28% versus 0.5-3%). The behavior of each congener was dose-dependent; therefore, extrapolation of high-dose experimental data should be used with caution.

An introduction to digital cameras.

BACKGROUND AND OBJECTIVES: People in all walks of life are using digital cameras instead of the traditional film cameras. Reasons include simplicity of use, ease of development, ability to incorporate the pictures into documents, potential to edit the pictures easily, and capability to send them by e-mail. This article will briefly discuss digital cameras, how they work, what they can do, and what you should look for in one. Editor's Note: This is the fourth in a series of articles demonstrating and describing information technology. The articles include nontechnical information and are geared toward the computer novice with interest in regional anesthesia and pain medicine.

Fragmentation of 3,7-dialkyl-1,5-diphenyl-3,7-diazabicyclo[3.3. 1]nonan-9-ones under electron ionization.

A series of 3,7-dialkyl-1,5-diphenyl-3,7-diazabicyclo[3.3. 1]nonan-9-ones was prepared, and the details of their fragmentation under electron ionization (EI) were elucidated. The molecular ions of each compound under consideration were quite abundant in their EI spectra. Full-scan spectra exhibited a number of fragment ions which were clearly assigned using MS/MS and accurate mass measurements. The basic fragmentation of 3,7-dialkyl-1,5-diphenylbispidinones was due to the cleavage of C(1)-C(2) bond followed by a hydrogen migration similar to an odd-electron McLafferty rearrangement. Alternatively, the C(1)-C(2) bond cleavage was followed by the elimination of an imine molecule, Alk-N=CH(2). Further fragmentation resulted in ions at m/z 234 and 103, present in the spectra of all the compounds under study. The fragmentation pathways proposed in this paper are based on the substituent shifts, accurate mass measurements and collision-induced dissociation spectra of selected ions. The results of the present work can be useful in selecting the fragment ions suitable for identification and quantitation of bispidinones in biological matrices.

Tuberous sclerosis type 1: three novel mutations detected in exon 15 by a combination of HDA and TGGE.

Tuberous sclerosis (TSC) is an autosomal dominant disorder which is genetically heterogeneous with two genes, TSC1 and TSC2. TSC1 consists of 23 exons with exon 15 being the largest one comprising 559 bp. Representing 16% of the coding region exon 15 harbors 37% of the already identified point mutations in TSC1. Mutation screening of large DNA fragments as TSC1 exon 15 by SSCP has been a problem because of the low sensitivity of this method without subdivision. Therefore, we simultaneously performed heteroduplex analysis (HDA) and temperature gradient gel electrophoresis (TGGE) which are both more suitable for evaluation of fragments of this size. DNA samples of 159 patients with the clinical diagnosis of TSC were screened and a total of seven different mutations in nine unrelated cases were identified, including the three novel mutations 1754delT, 1836delT and R500Q. Comparing the two methods applied, HDA showed a higher sensitivity in detecting frameshift mutations, while TGGE seemed to be more sensitive for the detection of base exchanges. We conclude that the combination of these two methods is appropriate to reach a high degree of sensitivity for the detection of all types of small mutations in large DNA fragments.

Storage of cord blood attracts private-sector interest.

Storage of cord blood from their babies can cost parents several hundred dollars, and some private companies are already offering the service. Janis Hass reports that some Canadian specialists question the value of the banks.

Mechanisms of seizure disorders.

Epilepsy, one of the most common neurologic disorders treated by veterinarians, is also one of the least understood. A dysregulation of neural excitability appears to underlie most seizures; yet, it is still not clear whether the disorder is one of excess excitation, failure of inhibition, or a combination of both. This paper presents normal neural physiology followed by current theories regarding the pathophysiology of epilepsy so that the reader may better understand the rationale explained in later chapters regarding the choice of anticonvulsant therapies.

Epilepsy resistant to anticonvulsant therapy.

The objective when treating a patient with refractory epilepsy is to control the seizures without drug toxicity. This is accomplished in a stepwise fashion: 1) use a drug known to be effective in the species being treated, 2) verify that the owner is complying with the prescribed dosage regimen, 3) monitor serum drug levels with samples taken at trough blood concentrations, 4) observe for adverse drug reactions/interactions, and 5) test for metabolic or structural brain injuries that would explain the poor drug response. By following these steps and individualizing the treatment for each patient, you should be able to obtain seizure control in the majority of patients.