Outflow tract tachycardia with R/S transition in lead V3: six different anatomic approaches for successful ablation.

OBJECTIVES The aim of this study was to analyze different anatomic mapping approaches for successful ablation of outflow tract tachycardia with R/S transition in lead V(3). BACKGROUND Idiopathic ventricular tachycardia can originate from different areas in the outflow tract, including the right and left ventricular endocardium, the epicardium, the pulmonary artery, and the aortic sinus of Valsalva. Although electrocardiographic criteria may be helpful in predicting the area of origin, sometimes the focus is complex to determine, especially when QRS transition in precordial leads is in V(3). METHODS We analyzed surface electrocardiograms of 33 successfully ablated patients with outflow tract tachycardia: 20 from the right ventricular outflow tract (RVOT) and 13 from different sites. The R/S transition was determined, and the different anatomic approaches needed for successful catheter ablation were studied. RESULTS Overall, R/S transition in lead V(3) was present in 19 (58%) of all patients. In these patients, mapping was started and successfully completed in the RVOT in 11 of 19 (58%) patients. The remaining eight patients with R/S transition in lead V(3) needed five additional anatomic accesses for successful ablation: from the left ventricular outflow tract (n = 3), aortic sinus of Valsalva (n = 2), coronary sinus (n = 1), the epicardium via pericardial puncture (n = 1), and the trunk of the pulmonary artery (n = 1), respectively. CONCLUSIONS A R/S transition in lead V(3) is common. In patients with outflow tract tachycardia with R/S transition in lead V(3), a stepwise endocardial and epicardial mapping through up to six anatomic approaches can lead to successful radiofrequency catheter ablation.

Imagery of a moving object: the role of occipital cortex and human MT/V5+

Visual imagery – similar to visual perception – activates feature-specific and category-specific visual areas. This is frequently observed in experiments where the instruction is to imagine stimuli that have been shown immediately before the imagery task. Hence, feature-specific activation could be related to the short-term memory retrieval of previously presented sensory information. Here, we investigated mental imagery of stimuli that subjects had not seen before, eliminating the effects of short-term memory. We recorded brain activation using fMRI while subjects performed a behaviourally controlled guided imagery task in predefined retinotopic coordinates to optimize sensitivity in early visual areas. Whole brain analyses revealed activation in a parieto-frontal network and lateral–occipital cortex. Region of interest (ROI) based analyses showed activation in left hMT/V5+. Granger causality mapping taking left hMT/V5+ as source revealed an imagery-specific directed influence from the left inferior parietal lobule (IPL). Interestingly, we observed a negative BOLD response in V1–3 during imagery, modulated by the retinotopic location of the imagined motion trace. Our results indicate that rule-based motion imagery can activate higher-order visual areas involved in motion perception, with a role for top-down directed influences originating in IPL. Lower-order visual areas (V1, V2 and V3) were down-regulated during this type of imagery, possibly reflecting inhibition to avoid visual input from interfering with the imagery construction. This suggests that the activation in early visual areas observed in previous studies might be related to short- or long-term memory retrieval of specific sensory experiences.

Gustatory dysfunction after mandibular zoster

Varicella zoster, limited to the mandibular nerve, is rare. Classical symptoms are pain, hypesthesia and vesicular eruption restricted to the third trigeminal segment (V3). Little is known on taste affection after mandibular nerve zoster. We report two cases of patients suffering from mandibular zoster associated with subjective taste disorder. In both cases, gustatory measures confirmed ipsilateral hemiageusia of the anterior two-thirds of the tongue. After 2 months, the symptoms regressed and psychophysical measures came back to normal values, whereas post-zoster neuralgia lasted for more than 1 year. Gustatory dysfunction is a possible symptom after mandibular nerve zoster. In contrast to post-zoster neuralgia, taste function seems to recover quickly.

Callosal connections of primary visual cortex predict the spatial spreading of binocular rivalry across the visual hemifields

In binocular rivalry, presentation of different images to the separate eyes leads to conscious perception alternating between the two possible interpretations every few seconds. During perceptual transitions, a stimulus emerging into dominance can spread in a wave-like manner across the visual field. These traveling waves of rivalry dominance have been successfully related to the cortical magnification properties and functional activity of early visual areas, including the primary visual cortex (V1). Curiously however, these traveling waves undergo a delay when passing from one hemifield to another. In the current study, we used diffusion tensor imaging (DTI) to investigate whether the strength of interhemispheric connections between the left and right visual cortex might be related to the delay of traveling waves across hemifields. We measured the delay in traveling wave times (ΔTWT) in 19 participants and repeated this test 6 weeks later to evaluate the reliability of our behavioral measures. We found large interindividual variability but also good test-retest reliability for individual measures of ΔTWT. Using DTI in connection with fiber tractography, we identified parts of the corpus callosum connecting functionally defined visual areas V1-V3. We found that individual differences in ΔTWT was reliably predicted by the diffusion properties of transcallosal fibers connecting left and right V1, but observed no such effect for neighboring transcallosal visual fibers connecting V2 and V3. Our results demonstrate that the anatomical characteristics of topographically specific transcallosal connections predict the individual delay of interhemispheric traveling waves, providing further evidence that V1 is an important site for neural processes underlying binocular rivalry.

S-0 and S-1 State Structure, Methyl Torsional Barrier Heights, and Fast Intersystem Crossing Dynamics of 5-Methyl-2-hydroxypyrimidine

We report the analysis of the SI So rotational band contours of jet-cooled 5-methyl-2-hydroxypyrimidine (5M2HP), the enol form of deoxythymine. Unlike thymine, which exhibits a structureless spectrum, the vibronic spectrum of 5M2HP is well structured, allowing us to determine the rotational constants and the methyl group torsional barriers in the S-0 and S-1 states. The 0(0)(0), 6a(0)(1), 6b(0)(1), and 14(0)(1) band contours were measured at 900 MHz (0.03 cm(-1)) resolution using mass-specific two-color resonant two-photon ionization (2C-R2PI) spectroscopy. All four bands are polarized perpendicular to the pyrimidine plane (>90% c type), identifying the S-1 <- S-0 excitation of 5M2HP as a 1n pi* transition. All contours exhibit two methyl rotor subbands that arise from the lowest 5-methyl torsional states 0A '' and 1E ''. The S-0 and S-1 state torsional barriers were extracted from fits to the torsional subbands. The 3-fold barriers are V-3 '' = 13 cm(-1) and V3' = SI cm(-1); the 6-fold barrier contributions V-6 '' and V-6' are in the range of 2-3 cm(-1) and are positive in both states. The changes of A, B, and C rotational constants upon S-1 <- S-0 excitation were extracted from the contours and reflect an "anti-quinoidal" distortion. The 0(0)(0) contour can only be simulated if a 3 GHz Lorentzian line shape is included, which implies that the S-1(1n pi*) lifetime is similar to 55 ps. For the 6a(0)(1) and 6b(0)(1) bands, the Lorentzian component increases to 5.5 GHz, reflecting a lifetime decrease to similar to 30 ps. The short lifetimes are consistent with the absence of fluorescence from the 1n pi* state. Combining these measurements with the previous observation of efficient intersystem crossing (ISC) from the Si state to a long-lived T-1((3)n pi*) state that lies similar to 2200 cm(-1) below [S. Lobsiger, S. et al. Phys. Chem. Chem. Phys. 2010, 12, 5032] implies that the broadening arises from fast intersystem crossing with k(ISC) approximate to 2 x 10(10) s(-1). In comparison to 5-methylpyrimidine, the ISC rate is enhanced by at least 10 000 by the additional hydroxy group in position 2.

Orientation-selective functional magnetic resonance imaging adaptation in primary visual cortex revisited

The processing of orientations is at the core of our visual experience. Orientation selectivity in human visual cortex has been inferred from psychophysical experiments and more recently demonstrated with functional magnetic resonance imaging (fMRI). One method to identify orientation-selective responses is fMRI adaptation, in which two stimuli—either with the same or with different orientations—are presented successively. A region containing orientation-selective neurons should demonstrate an adapted response to the “same orientation” condition in contrast to the “different orientation” condition. So far, human primary visual cortex (V1) showed orientation-selective fMRI adaptation only in experimental designs using prolonged pre-adaptation periods (∼40 s) in combination with top-up stimuli that are thought to maintain the adapted level. This finding has led to the notion that orientation-selective short-term adaptation in V1 (but not V2 or V3) cannot be demonstrated using fMRI. The present study aimed at re-evaluating this question by testing three differently timed adaptation designs. With the use of a more sensitive analysis technique, we show robust orientation-selective fMRI adaptation in V1 evoked by a short-term adaptation design.

A novel SCN5A mutation, F1344S, identified in a patient with Brugada syndrome and fever-induced ventricular fibrillation

OBJECTIVE: Brugada syndrome (BS) is an inherited electrical cardiac disorder characterized by right bundle branch block pattern and ST segment elevation in leads V1 to V3 on surface electrocardiogram that can potentially lead to malignant ventricular tachycardia and sudden cardiac death. About 20% of patients have mutations in the only so far identified gene, SCN5A, which encodes the alpha-subunit of the human cardiac voltage-dependent sodium channel (hNa(v)1.5). Fever has been shown to unmask or trigger the BS phenotype, but the associated molecular and the biophysical mechanisms are still poorly understood. We report on the identification and biophysical characterization of a novel heterozygous missense mutation in SCN5A, F1344S, in a 42-year-old male patient showing the BS phenotype leading to ventricular fibrillation during fever. METHODS: The mutation was reproduced in vitro using site-directed mutagenesis and characterized using the patch clamp technique in the whole-cell configuration. RESULTS: The biophysical characterization of the channels carrying the F1344S mutation revealed a 10 mV mid-point shift of the G/V curve toward more positive voltages during activation. Raising the temperature to 40.5 degrees C further shifted the mid-point activation by 18 mV and significantly changed the slope factor in Na(v)1.5/F1344S mutant channels from -6.49 to -10.27 mV. CONCLUSIONS: Our findings indicate for the first time that the shift in activation and change in the slope factor at a higher temperature mimicking fever could reduce sodium currents' amplitude and trigger the manifestation of the BS phenotype.

Vertebral artery dissection: presenting findings and predictors of outcome

BACKGROUND AND PURPOSE: Few data exist about clinical, radiologic findings, clinical outcome, and its predictors in patients with spontaneous vertebral artery dissection (sVAD). METHODS: Clinical characteristics, imaging findings, 3-month outcomes, and its predictors were investigated in consecutive patients with sVAD. RESULTS: One hundred sixty-nine patients with 195 sVAD were identified. Brain ischemia occurred in 131 patients (77%; ischemic stroke, n=114, 67%; transient ischemic attack, n=17, 10%). Three patients with ischemic stroke showed also signs of subarachnoid hemorrhage (SAH); 3 (2%) had SAH without ischemia. The 134 patients with brain ischemia or SAH had head and/or neck pain in 118 (88%) and pulsatile tinnitus in seven (5%) patients. The remaining 35 patients (21%) had isolated head and/or neck pain in 21 (12%) cases, asymptomatic sVAD in 13 (8%), and cervical radiculopathy in one case (1%). Location of sVAD was more often in the pars transversaria (V2; 35%) or atlas loop (V3; 34%) than in the prevertebral (V1; 20%) or intracranial (V4; 11%) segment (P=0.0001). Outcome was favorable (modified Rankin scale score 0 or 1) in 88 (82%) of 107 ischemic stroke patients with follow up. Two (2%) patients died. Low baseline National Institutes of Health Stroke Scale score (P<0.0001) and younger age (P=0.007) were independent predictors of favorable outcome. CONCLUSIONS: sVAD is predominantly located in the pars transversaria (V2) or the atlas loop (V3). Most patients show posterior circulation ischemia. Favorable outcome is observed in most ischemic strokes and independently predicted by low National Institutes of Health Stroke Scale score and younger age.

Functional properties of multiple isoforms of human divalent metal-ion transporter 1 (DMT1)

DMT1 (divalent metal-ion transporter 1) is a widely expressed metal-ion transporter that is vital for intestinal iron absorption and iron utilization by most cell types throughout the body, including erythroid precursors. Mutations in DMT1 cause severe microcytic anaemia in animal models. Four DMT1 isoforms that differ in their N- and C-termini arise from mRNA transcripts that vary both at their 5'-ends (starting in exon 1A or exon 1B) and at their 3'-ends giving rise to mRNAs containing (+) or lacking (-) the 3'-IRE (iron-responsive element) and resulting in altered C-terminal coding sequences. To determine whether these variations result in functional differences between isoforms, we explored the functional properties of each isoform using the voltage clamp and radiotracer assays in cRNA-injected Xenopus oocytes. 1A/IRE+-DMT1 mediated Fe2+-evoked currents that were saturable (K(0.5)(Fe) approximately 1-2 microM), temperature-dependent (Q10 approximately 2), H+-dependent (K(0.5)(H) approximately 1 muM) and voltage-dependent. 1A/IRE+-DMT1 exhibited the provisional substrate profile (ranked on currents) Cd2+, Co2+, Fe2+, Mn2+>Ni2+, V3+>>Pb2+. Zn2+ also evoked large currents; however, the zinc-evoked current was accounted for by H+ and Cl- conductances and was not associated with significant Zn2+ transport. 1B/IRE+-DMT1 exhibited the same substrate profile, Fe2+ affinity and dependence on the H+ electrochemical gradient. Each isoform mediated 55Fe2+ uptake and Fe2+-evoked currents at low extracellular pH. Whereas iron transport activity varied markedly between the four isoforms, the activity for each correlated with the density of anti-DMT1 immunostaining in the plasma membrane, and the turnover rate of the Fe2+ transport cycle did not differ between isoforms. Therefore all four isoforms of human DMT1 function as metal-ion transporters of equivalent efficiency. Our results reveal that the N- and C-terminal sequence variations among the DMT1 isoforms do not alter DMT1 functional properties. We therefore propose that these variations serve as tissue-specific signals or cues to direct DMT1 to the appropriate subcellular compartments (e.g. in erythroid cells) or the plasma membrane (e.g. in intestine).

Spectrum and prevalence of mutations involving BrS1- through BrS12-susceptibility genes in a cohort of unrelated patients referred for Brugada syndrome genetic testing: implications for genetic testing

OBJECTIVES The aim of this study was to provide the spectrum and prevalence of mutations in the 12 Brugada syndrome (BrS)-susceptibility genes discovered to date in a single large cohort of unrelated BrS patients. BACKGROUND BrS is a potentially lethal heritable arrhythmia syndrome diagnosed electrocardiographically by coved-type ST-segment elevation in the right precordial leads (V1 to V3; type 1 Brugada electrocardiographic [ECG] pattern) and the presence of a personal/family history of cardiac events. METHODS Using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing, comprehensive mutational analysis of BrS1- through BrS12-susceptibility genes was performed in 129 unrelated patients with possible/probable BrS (46 with clinically diagnosed BrS [ECG pattern plus personal/family history of a cardiac event] and 83 with a type 1 BrS ECG pattern only). RESULTS Overall, 27 patients (21%) had a putative pathogenic mutation, absent in 1,400 Caucasian reference alleles, including 21 patients with an SCN5A mutation, 2 with a CACNB2B mutation, and 1 each with a KCNJ8 mutation, a KCND3 mutation, an SCN1Bb mutation, and an HCN4 mutation. The overall mutation yield was 23% in the type 1 BrS ECG pattern-only patients versus 17% in the clinically diagnosed BrS patients and was significantly greater among young men<20 years of age with clinically diagnosed BrS and among patients who had a prolonged PQ interval. CONCLUSIONS We identified putative pathogenic mutations in ∼20% of our BrS cohort, with BrS genes 2 through 12 accounting for <5%. Importantly, the yield was similar between patients with only a type 1 BrS ECG pattern and those with clinically established BrS. The yield approaches 40% for SCN5A-mediated BrS (BrS1) when the PQ interval exceeds 200 ms. Calcium channel-mediated BrS is extremely unlikely in the absence of a short QT interval.

Does emergency vaccination make sense as a supporting element in control of foot-and-mouth disease in Switzerland

The outbreak of foot and mouth disease (FMD) in Great Britain in 2001 let to discussions and especially emergency vaccination was deemed as an alternative to the culling of vast numbers of healthy animals. The project emergency vaccination for FMD in Switzerland was conducted to compare the effectiveness of conventional control strategies during a FMD outbreak alone and with ring vaccination of 3 km and 10 km, respectively. The results of this project showed that emergency vaccination conducted at the beginning of an epidemic was not favorable compared to conventional disease control strategy in Switzerland. In case of an advanced FMD epidemic, a 10 km ring vaccination could support the disease control in a positive way. However, the goal of emergency vaccination to save animal live can hardly be achieved due to actual legal basis and the consequent restriction measures within vaccination zones which will lead to welfare culling.

Kyzylkumite, Ti2V3+O5(OH): new structure type, modularity and revised formula

The crystal structure of kyzylkumite, ideally Ti2V3+O5(OH), from the Sludyanka complex in South Baikal, Russia was solved and refined (including the hydrogen atom position) to an agreement index, R1, of 2.34 using X-ray diffraction data collected on a twinned crystal. Kyzylkumite crystallizes in space group P21/c, with a = 8.4787(1), b = 4.5624(1), c = 10.0330(1) Å, β = 93.174(1)°, V = 387.51(1) Å3 and Z = 4. Tivanite, TiV3+O3OH, and kyzylkumite have modular structures based on hexagonal close packing of oxygen, which are made up of rutile TiO2 and montroseite V3+O(OH) slices. In tivanite the rutile:montroseite ratio is 1:1, in kyzylkumite the ratio is 2:1. The montroseite module may be replaced by the isotypic paramontroseite V4+O2 module, which produces a phase with the formula Ti2V4+O6. In the metamorphic rocks of the Sludyanka complex, vanadium can be present as V4+ and V3+ within the same mineral (e.g. in batisivite, schreyerite and berdesinskiite). Kyzylkumite has a flexible composition with respect to the M4+/M3+ ratio. The relationship between kyzylkumite and a closely related Be-bearing kyzylkumite-like mineral with an orthorhombic norbergite-type structure from Byrud mine, Norway is discussed. Both minerals have similar X-ray powder diffraction patterns.