Anatomical and fMRI-network comparison of multiple DLPFC targeting strategies for repetitive transcranial magnetic stimulation treatment of depression.

BACKGROUND: The efficacy of repetitive transcranial magnetic stimulation (rTMS) for depression may vary depending on the subregion stimulated within the dorsolateral prefrontal cortex (DLPFC). Clinical TMS typically uses scalp-based landmarks for DLPFC targeting, rather than individualized MRI guidance. OBJECTIVE: In rTMS patients, determine the brain systems targeted by multiple DLPFC stimulation rules by computing several surrogate measures: underlying brain targets labeled with connectivity-based atlases, subgenual cingulate anticorrelation strength, and functionally connected networks. METHODS: Forty-nine patients in a randomized controlled trial of rTMS therapy for treatment resistant major depression underwent structural and functional MRI. DLPFC rules were applied virtually using MR-image guidance. Underlying cortical regions were labeled, and connectivity with the subgenual cingulate and whole-brain computed. RESULTS: Scalp-targeting rules applied post hoc to these MRIs that adjusted for head size, including Beam F3, were comparably precise, successful in directly targeting classical DLPFC and frontal networks, and anticorrelated with the subgenual cingulate. In contrast, all rules involving fixed distances introduced variability in regions and networks targeted. The 5 cm rule targeted a transitional DLPFC region with a different connectivity profile from the adjusted rules. Seed-based connectivity analyses identified multiple regions, such as posterior cingulate and inferior parietal lobe, that warrant further study in order to understand their potential contribution to clinical response. CONCLUSION: EEG-based rules consistently targeted DLPFC brain regions with resting-state fMRI features known to be associated with depression response. These results provide a bridge from lab to clinic by enabling clinicians to relate scalp-targeting rules to functionally connected brain systems.

Targeting location relates to treatment response in active but not sham rTMS stimulation.

BACKGROUND: Precise targeting of brain functional networks is believed critical for treatment efficacy of rTMS (repetitive pulse transcranial magnetic stimulation) in treatment resistant major depression. OBJECTIVE: To use imaging data from a "failed" clinical trial of rTMS in Veterans to test whether treatment response was associated with rTMS coil location in active but not sham stimulation, and compare fMRI functional connectivity between those stimulation locations. METHODS: An imaging substudy of 49 Veterans (mean age, 56 years; range, 27-78 years; 39 male) from a randomized, sham-controlled, double-blinded clinical trial of rTMS treatment, grouping participants by clinical response, followed by group comparisons of treatment locations identified by individualized fiducial markers on structural MRI and resting state fMRI derived networks. RESULTS: The average stimulation location for responders versus nonresponders differed in the active but not in the sham condition (P = .02). The average responder location derived from the active condition showed significant negative functional connectivity with the subgenual cingulate (P < .001) while the nonresponder location did not (P = .17), a finding replicated in independent cohorts of 84 depressed and 35 neurotypical participants. The responder and nonresponder stimulation locations evoked different seed based networks (FDR corrected clusters, all P < .03), revealing additional brain regions related to rTMS treatment outcome. CONCLUSION: These results provide evidence from a randomized controlled trial that clinical response to rTMS is related to accuracy in targeting the region within DLPFC that is negatively correlated with subgenual cingulate. These results support the validity of a neuro-functionally informed rTMS therapy target in Veterans.

The role of trace elements and phosphates in the synthesis of vascular-permeability factor by Vibrio cholerae.

Trace element and phosphate requirements for the synthesis of vascular-permeability factor (PF) by Vibrio cholerae strains B1307 and VC12 were investigated. While magnesium appeared to be indispensable for strain VC12, small amounts of PF were synthesised by strain B1307 in the presence of iron, zinc and manganese. However, even in the latter strain, maximum synthesis was recorded only in magnesium-containing media. Phosphates in the range 0.75-6.00mM controlled the synthesis of PF by both strains.

Conversion of p-coumarate into caffeate by Streptomyces nigrifaciens. Purification and properties of the hydroxylating enzyme.

1. An enzyme responsible for the conversion of p-coumarate into caffeate was purified 97-fold from Streptomyces nigrifaciens. The enzyme had a molecular weight of 18000 as determined by Sephadex G-100 gel filtration and was homogeneous on polyacrylamide-gel electrophoresis. 2. The preparation exhibited both p-coumarate hydroxylase and caffeate oxidase activities. 3. Stoicheiometry of the reaction indicated a mono-oxygenase-mediated catalysis consuming 1mol of O(2)/mol of substrate hydroxylated. 4. NADH, NADPH, tetrahydropteroylglutamate or ascorbate act as electron donors for the reaction, ascorbate being inhibitory at higher concentrations. 5. The optimum enzyme activity was at about pH7.7 and 40 degrees C, with an activation energy of 39kJ/mol. 6. Monophenols such as p-hydroxyphenylpropionate, p-hydroxyphenylacetate, l-tyrosine and dl-p-hydroxyphenyl-lactate were also hydroxylated by the preparation, in addition to p-coumarate. 7. The enzyme was a copper protein having 0.38% copper in a bound form. 8. Thiol-group inhibitors did not affect the reaction. 9. The relationship of the enzyme to other hydroxylases is discussed.

Role of pectinolytic yeasts in the degradation of mucilage layer of Coffea robusta cherries.

Pectinolytic yeasts, Saccharomyces marxianus, S. bayanus, S. cerevisiae var. ellipsoideus, and Schizosaccharomyces sp., predominated in the natural fermentation of coffee cherries of Coffea robusta variety grown in Chikmagalur district of Mysore State, India. These yeast species were found on the cherry surfaces, and evidence was adduced to show that the natural fermentation of coffee was the result of activity of microflora from the cherry surface itself rather than that of flora of air or water. Incorporation of pure cultures of Saccharomyces species was shown to aid the process when a mixture of all three species was used. An enzyme preparation from the Saccharomyces species was observed to hasten the mucilage-layer degradation.

Metabolism of saturated 1-14C-labelled fatty acids in the silkworm Bombyx mori L.

1. Only a small percentage of 1-(14)C-labelled saturated fatty acids injected in the silkworm is respired as carbon dioxide. 2. The rate of utilization of fatty acids is low both at the larval and pupal stages. 3. The insect has the ability to elongate C(12) and C(16) saturated fatty acids and to desaturate C(18) saturated fatty acids. 4. Much of the administered radioactivity is found in the triglyceride fraction, followed by the phospholipid and diglyceride fractions. 5. Diglycerides seem to be the transport form of fatty acids. 6. The insect seems to metabolize both natural and unnatural fatty acids in the same manner.