Despite the well-documented relationship of socioeconomic factors (SEF) to various health problems, the relationship of SEF to erectile dysfunction (ED) is not well understood. As such, the goals of this paper are: (1) to determine whether incident ED is more likely to occur among men with low SEF; and (2) to determine whether incident ED varies by SEF after taking into consideration other well-established ED risk factors that are also associated with SEF such as smoking, diabetes, and high blood pressure. We used data from 797 participants in the longitudinal population-based Massachusetts Male Aging Study (baseline 1987-1989, follow-up 1995-1997) who were free of ED at baseline and had complete data on ED and all risk factors. ED was determined by a self-administered questionnaire and its relationship to SEF was assessed using logistic regression. We first analyzed the age-adjusted relationship of education, income, and occupation to incidence of ED. The results show that men with low education (O.R. = 1.46, 95% C.I. = 1.02-2.08) or men in blue-collar occupations (O.R. = 1.68, 95% C.I. = 1.16-2.43) are significantly more likely to develop ED. For the multivariate model, due to multicollinearity among education, income, and occupation, we ran three separate models. After taking into consideration all the other risk factors--age, lifestyle and medical conditions--the effect of occupation remained significant. Men who worked in blue-collar occupations were one and a half times more likely to develop ED compared to men in white-collar occupations (O.R. = 1.55, 95% C.I. = 1.06-2.28).

Salmonella enteritidis thin fimbriae, SEF14, were found to be restricted to S. dublin and the predominantly poultry-associated members of the Salmonella O-serogroup D1, S. enteritidis, S. berta, S. gallinarum and S. pullorum, when tested by Western and ELISA analysis from among 90 Salmonella isolates of 42 serovars, as well as from members of several related genera of the Enterobacteriaceae. These five serovars and a single isolate of S. typhi (D1) were also detected by hybridization of genomic DNA from 732 Salmonella isolates of 117 serogroups to gene probes derived from the S. enteritidis sefA (fimbrin gene), sefB (chaperone) or sefC (outer membrane protein) genes encoding proteins involved in SEF14 biosynthesis. None of 250 Enterobacteriaceae or 27 other eubacterial isolates tested hybridized to the sef probes. The sefA, sefB and sefC genes were amplified from these six Salmonella serovars by PCR using primer pairs designed from sefA, sefB or sefC of S. enteritidis. DNA sequencing of sefA genes from these five serovars indicated limited sequence variability among sefA genes and recognition of individual base pairs which could potentially differentiate certain strains of S. enteritidis, S. dublin and S. gallinarum.

A highly reflective thick Ag island film (TAIF) sputter-grown on mica, consisting of unique large pseudotabular nanoislands, 60-200 nm across and 30-60 nm thick, produced an unusually strong surface enhanced fluorescence (SEF) for rhodamine dyes situated very close to (only approximately 10 A away from) the metal surface. A significantly greater part of the enhanced fluorescence was emitted into the back half space through TAIF and the mica substrate. The detailed fluorescence angular distribution was very similar to that of the light scattering by TAIF, suggesting that the enhanced emission originated from some large induced dipoles in TAIF. For reference, we also present a quantitative analysis of the fluorescent behavior of the same dye but directly coated on a reference glass surface. TAIF showed no distinct dipolar surface plasmon-like bands for excitation at normal incidence, and the light absorption by dye-coated TAIF could be described by simple superposition of the contribution of TAIF and that of the surface-bound dyes. However, the net dye absorptance was increased by 4-5 times due to the strong interactions of the dye transition dipoles with the TAIF-scattered fields. The estimated SEF quantum yield in the low dye coverage limit suggests a markedly high radiative yield of the induced dipole in TAIF around approximately 0.5.

Substantial disability in patients with hemianopia results from reduced visual perception. Previous studies have shown that these patients have impaired saccades. Improving exploratory eye movements with appropriate training of saccades may help to partially compensate for the visuoperceptive impairment during daily life activities. The changes in cortical control of eye movements that may be induced by these training strategies, however, are not known. We used functional magnetic resonance imaging (fMRI) to study the training effects of eye-movement training on cortical control of saccades. Brain activation during visually guided saccades was measured in eight patients with an occipital cortical lesion causing homonymous hemianopia. Starting 8 weeks after the stroke, patients received 4 weeks of visual field training. The fMRI measurements were performed at baseline and after training. In five patients, follow-up fMRI was performed 4 weeks after the end of training. Differences in activation between rest and saccades as well as before and after training were assessed with statistical parametric mapping software (SPM'99). Twelve healthy subjects were scanned twice at a 4-week interval. In patients, significant activation at baseline was found in the frontal and parietal eye fields (FEF and PEF, respectively) bilaterally and in the supplementary eye field (SEF). Immediately after training, an area of increased activation was found in the left extrastriate cortex of the affected hemisphere. At follow-up, relatively more activation was found in the right peristriate cortex and in the SEF of the unaffected side. A relative decrease of activation was found in the left FEF. In this group of patients, eye-movement training induced altered brain activation in the striate and extrastriate cortex as well as in oculomotor areas.

Neural regions in the dorsomedial frontal cortex (DMFC), including the supplementary eye field (SEF) and the presupplementary motor area (pre-SMA), are likely candidates for generating top-down control of saccade target selection. To investigate this, we applied electrical microstimulation to these structures while saccades were being planned to visual targets. Stimulation administered to superficial and lateral DMFC sites that were within or close to the SEF delayed ipsilateral and facilitated contralateral saccades. Facilitation was limited to saccades made toward targets in a narrow, contralateral movement field that had endpoints consistent with the goal of evoked saccades. Facilitation occurred with current delivered before target onset and delay with current applied after this time. Stimulation at deeper, medial sites that encompassed the pre-SMA resulted in mostly bilateral delay. The amount of delay at these sites was usually greater for ipsilateral saccades and increased with current amplitude. Changes in saccade latency were not accompanied by altered endpoint, trajectory, or peak velocity. The spatial specificity of SEF stimulation in inducing latency changes suggests that the SEF participates in selecting saccade goals. The less specific delay with pre-SMA stimulation suggests that it is involved in postponing visually guided saccades, thus likely permitting other oculomotor structures to select saccade goals.

BACKGROUND

Higher cortical function during sensory processing can be examined by recording specific somatosensory-evoked magnetic fields (SEFs) with magnetoencephalography (MEG). We evaluated whether, in extremely low-gestational-age (ELGA) infants, abnormalities in MEG-recorded SEFs at term age are associated with adverse neurodevelopment at 2 y of corrected age.

METHODS

SEFs to tactile stimulation of the index finger were recorded at term age in 30 ELGA infants (26.5 ± 1.2 wk, birth weight: 884 g ± 181 g). Neurodevelopment was evaluated at 2 y of corrected age. Controls were 11 healthy term infants.

RESULTS

In nine of the ELGA infants (30.0%), SEFs were categorized as abnormal on the basis of lack of response from secondary somatosensory cortex (SII). At 2 y, these infants had a significantly worse mean developmental quotient and locomotor subscale on the Griffiths Mental Development Scales than the ELGA infants with normal responses. Mild white matter abnormalities in magnetic resonance imaging at term age were detected in 21% of infants, but these abnormalities were not associated with adverse neurodevelopment.

CONCLUSIONS

Abnormal SII responses at term predict adverse neuromotor development at 2 y of corrected age. This adverse development may not be foreseen with conventional neuroimaging methods, suggesting a role for evaluating SII responses in the developmental risk assessment of ELGA infants.

The nucleotide sequence relatedness between the chromosome of Salmonella typhi and the virulence plasmid of Salmonella enteritidis was investigated using short DNA probes of < 2 kb covering the whole virulence plasmid sequence. Only one homologous region was detected. This region was subsequently cloned and partially sequenced. Sequences closely related to the pefl gene and the ORFs orf7, orf8 and orf9, which are located downstream of the fimbrial pef operon of the Salmonella typhimurium virulence plasmid, were detected. Sequencing of the cloned S. typhi DNA fragment also revealed identity with genes of the fimbrial sef operon characterized in the chromosome of S. enteritidis. These nucleotide sequences mapped upstream of the S. typhi chromosomal region homologous to the S. enteritidis virulence plasmid. The general organization of the cloned S. typhi chromosomal fragment was similar to the fimbriae-encoding region of the S. typhimurium virulence plasmid. The deduced product of orf8 in the S. typhimurium virulence plasmid, as well as those of the corresponding ORFs in the homologous region of the S. typhi chromosome and in the S. enteritidis virulence plasmid (designated dlt and dlp, respectively), appeared to be related to the thioredoxin family of thiol: disulphide oxidoreductases. The dlp gene was able to complement the DTT-sensitive phenotype, the inability to metabolize glucose 1-phosphate and the low alkaline phosphatase activity of a dsbA mutant of Escherichia coli. The dlt gene partially complemented the lack of alkaline phosphatase activity, but not the other mutant phenotypes. The products of both genes could be detected using the T7 RNA polymerase promoter expression system. The estimated molecular masses of the products of the dlt and dlp genes by SDS-PAGE were 26 and 23 kDa, respectively, the first being in agreement with the deduced amino acid sequence and the latter, somewhat smaller. The processing of a possible leader peptide in the Dlp protein, but not in the Dlt protein, could be responsible for this difference. The Dlp protein appeared as a doublet band on SDS-PAGE, which is characteristic of the oxidized and reduced states of this kind of protein.

We aimed to compare the effects of distraction on pain-related somatosensory evoked magnetic fields (pain SEF) following painful electrical stimulation with simultaneous recordings of evoked potentials (pain SEP). Painful electrical stimuli were applied to the right index finger of eleven healthy subjects. A table with 25 random two-digit numbers was shown to the subjects, who were asked to add 5 numbers of each line in their mind (calculation task) or to memorize the numbers (memorization task) during the recording. In the SEF recording, 3 short-latency components within 50 ms of the stimulation were generated in the primary sensory cortex (SI) of the hemisphere contralateral to the stimulated finger. Middle-latency components between 100 and 250 ms after the stimuli were recorded from the secondary somatosensory cortex (SII) in the bilateral hemispheres or the cingulate cortex. No SEF components were significantly affected by either task. In the SEP recording, the middle-latency components (N140 and P230) were identified as being maximal around the vertex. Amplitudes of the N140 and P230 were not affected by each task, but the peak-to-peak amplitude (N140-P230) was significantly decreased by both the calculation and memorization tasks, particularly by the former. Subjective pain rating was decreased in both the calculation and memorization tasks, particularly in the former. We concluded that distraction tasks reduced activities in the limbic system, in which the middle-latency EEG component probably generated, while neither the short-latency SEF components generated in SI nor the primary pain-related SEF components generated in SII-insula are affected.

In previous reports, we showed the involvement of area 8B neurons in both spontaneous ear and eye movement and in auditory information processing. Audition-related cells responded to complex environmental stimuli, but not to pure tones, and their activity changed during visual fixation as a possible inhibitory expression of the engagement of attention. We observed auditory, auditory-motor and motor cells for both eye and ear movements. This finding suggests that area 8B may be involved in the integration of auditory input with ear and eye motor output. In this paper, we extended these previous studies by examining area 8B activity in relation to auditive orienting behaviour, as well as the ocular orientation (i.e., visual fixation) studied previously. Visual fixation led to inhibition of activity in auditory and auditory-motor cells, which suggests that attention may be involved in both, maintaining the eye position and reducing the response of these cell types. Accordingly, during a given task or natural behaviour, spatial attention seems to affect more than one sensorimotor channel simultaneously. These data add to our understanding of how the neural network, through a two-channel attentive process, accomplishes to switch between two effectors, namely eyes and ears. Considering the functional, anatomical and cytoarchitectonic differences among the frontal eye field (FEF), the supplementary eye field (SEF) and area 8B, we propose to consider area 8B as a separate premotor ear-eye field (PEEF).

Minimum alveolar concentration (MAC) has been traditionally used to measure the potency of an inhalational anesthetic agent. Recently, bispectral index (BIS) derived from the frontal cortical electroencephalogram has been used frequently for quantifying the hypnotic component of anesthesia. The present study was designed to examine the BIS values produced by equi-MAC concentrations of halothane and isoflurane. In 34 patients undergoing spinal surgery, BIS and spectral edge frequency (SEFSEFSEF(95) values were significantly lower under isoflurane compared with halothane anesthesia both during wash-in and wash-out phases (P<0.001). For a given anesthetic agent, BIS values were comparable at equi-MAC concentrations during wash-in and wash-out phases. In conclusion, BIS values are significantly lower under isoflurane compared with halothane anesthesia at similar MAC concentrations. For a given anesthetic agent and a given MAC concentration, the BIS values are similar during wash-in and wash-out phases of anesthesia.

Although biomechanical studies of the normal rat vein wall have been reported (Weizsacker, 1988; Plante, 2002), there are no published studies that have investigated the mechanical effects of thrombus formation on murine venous tissue. In response to the lack of knowledge concerning the mechanical consequences of thrombus resolution, distinct thrombus-induced changes in the biomechanical properties of the murine vena cava were measured via biaxial stretch experiments. These data served as input for strain energy function (SEF) fitting and modeling (Gasser et al., 2006). Statistical differences were observed between healthy and diseased tissue with respect to the structural coefficient that represents the response of the non-collagenous, isotropic ground substance. Alterations following thrombus formation were also noted for the SEF coefficient which describes the anisotropic contribution of the fibers. The data indicate ligation of the vena cava leads to structural alterations in the ground substance and collagen fiber network.

White matter thalamo-cortical fibers allow the communication of distant brain regions by carrying neuronal signals. Mapping non-invasively the information flow within white matter fibers is regarded so far as impossible. We investigated here whether information flow propagating along thalamo-cortical fibers can be detected using magnetoencephalography (MEG). Somatosensory evoked fields (SEFs) were recorded from healthy subjects and a patient with a unilateral, prenatally acquired, white matter lesion, which had induced the development of an abnormal trajectory of thalamo-cortical fibers. Equivalent current dipole (ECD) was used to model sources of SEFs. ECD at ~15 ms after stimulus onset was located within or close to the contralateral thalamus at the proximity of a hemodynamic response detected during a similar fMRI experiment. At the M20 peak latency, ECD was localized within the hand area of the contralateral primary somatosensory cortex (Brodmann area 3b (BA3b)). In healthy subjects, ECD changed dynamically position from thalamus to BA3b following a curved path, which was partially overlapping the thalamo-cortical fibers reconstructed by tractography. In the patient, ECD followed a similar path only in the intact hemisphere. In the affected hemisphere, the dipole trajectory circumnavigated the extended lesion on its way to the preserved primary somatosensory cortex--similar to the trajectory findings. Evidence from different methodological approaches converges on the conclusion that MEG can track the afferent information flow along thalamo-cortical fibers and in contrast to the traditional view can localize under presuppositions deep thalamic sources.

OBJECTIVE

Rho guanidine triphosphatases (GTPases) are major regulators of cell migration. We investigated the cytoskeleton and Rho GTPases during cell migration and morphogenesis processes in isolated rat liver sinusoidal endothelial cells (LSECs) cultured on Matrigel while stimulated by the vascular endothelial growth factor (VEGF).

METHODS

To obtain primary monolayers, LSECs were cultured on Matrigel for 5-17 h with or without VEGF. Sinusoidal endothelial fenestrae (SEF) morphology was observed using scanning electron microscopy and transmission electron microscopy. RhoA, Rac1 and phosphorylated myosin light-chain kinase, Rho-binding domain of Rhotekin and the p21-binding domain of p21-activated protein kinase were analysed using Western blotting.

RESULTS

The LSECs showed cellular protrusions and or cords of aligned cells resembling primitive capillary-like structures, with SEF contraction. Time course analyses of Rac1 activation matched specific morphological changes. Rac1 activity increased progressively to 17 h in cells cultured without VEGF, but markedly increased at 7 h in the presence of VEGF. RhoA activity was slightly elevated at 5 h. The levels of endogenous caveolin-1 (CAV-1) expression increased in a time-dependent manner, reaching a peak at 7 h. CAV-1 expression occurred immediately before the formation of the capillary-like tube. Moreover, treatment with VEGF regulated CAV-1 expression in LSECs.

CONCLUSIONS

Spatial activation of Rac1 is involved in the formation of a capillary-like tubular network accompanying SEF contraction in LSECs, implying that endothelial migration and adhesion are necessary for LSECs tubular formation in the liver. CAV-1 might play an important positive role in the regulation of LSEC tubular formation.

OBJECTIVE

To characterise and quantify the EEG during sleep in healthy newborns in the early newborn period.

METHODS

Continuous multi-channel video-EEG data was recorded for up to 2 hours in normal newborns within 12 hours of birth. The total amount of active (AS) and quiet sleep (QS) was calculated in the first hour of recording. The EEG signal was quantitatively analysed for symmetry and synchrony. Spectral edge frequency (SEF), spectral entropy (H) and relative delta power (delta(R)) were calculated for a ten-minute segment of AS and QS in each recording. Paired t-test and Wilcoxon rank sum test were used for data analysis.

RESULTS

Thirty normal newborn babies were studied, 10 within 6 hours of birth and 20 between 6 and 12 hours. All babies showed continuous symmetrical and synchronous EEG activity and well-developed sleep-wake cycling (SWC) with the median percentage of AS--48.5% and QS--36.6%. Quantitative EEG analysis of sleep epochs showed that SEF and H were significantly higher (p<0.0001) and delta(R) was significantly lower (p<0.0001) in AS than in QS.

CONCLUSIONS

The normal newborn EEG shows symmetrical and synchronous continuous activity and well-developed SWC as early as within the first 6 hours of birth. Quantitative analysis of the EEG in the early postnatal period reveals differences in SEF, H and delta(R) for AS and QS periods.

CONCLUSIONS

These findings may have implications for quantitative analysis of the newborn EEG, including the EEG of babies with hypoxic ischaemic encephalopathy.

The somatosensory evoked magnetic field (SEF) following passive finger movement and electrical stimulation of finger was studied in 10 normal subjects. Four main components were identified in SEFs recorded at the hemisphere contralateral to the moved finger: 1M(P), 2M(P), 3M(P) and 4M(P). The 1M(P) was clearly identified only in three subjects and was smaller than other components. The equivalent current dipoles (ECDs) of 1M(P) were located around the finger area of the primary sensorimotor cortex and oriented either posteriorly or anteriorly. We speculate that it was generated in areas 3a or 2 of the primary sensory cortex. The 2M(P) and 3M(P) were usually combined as one large deflection with two peaks. Because the ECDs of 2M(P) and 3M(P) were located around the finger area of the sensorimotor cortex and both oriented posteriorly, they were considered to be generated in area 4 and/or 3b, and their activities have temporal overlapping. The 4M(P) has large inter-individual difference in terms of amplitude and latency. The ECD of 4M(P) was also located around the finger area of the primary sensorimotor cortex, and oriented anteriorly. The 4M(PI), the main component recorded from the hemisphere ipsilateral to the moved finger, was located in the upper bank of the sylvian fissure, probably the second sensory cortex (SII). Five components, 1M(E), 2M(E), 3M(E), 4M(E) and 4M(EI), corresponding to 1M(P), 2M(P), 3M(P), 4M(P) and 4M(PI), were identified following electrical stimulation of the same finger. However, SEFs following passive movement were clearly different from SEFs following electrical stimulation, in terms of waveforms and source locations, probably due to differences of ascending fibers and receptive fields.

OBJECTIVE

Dipole models, which are frequently used in attempts to solve the electromagnetic inverse problem, require explicit a priori assumptions about the cerebral current sources. This is not the case for solutions based on minimum-norm estimates. In the present study, we evaluated the spatial accuracy of the L2 minimum-norm estimate (MNE) in realistic noise conditions by assessing its ability to localize sources of evoked responses at the primary somatosensory cortex (SI).

METHODS

Multichannel somatosensory evoked potentials (SEPs) and magnetic fields (SEFs) were recorded in 5 subjects while stimulating the median and ulnar nerves at the left wrist. A Tikhonov-regularized L2-MNE, constructed on a spherical surface from the SEP signals, was compared with an equivalent current dipole (ECD) solution obtained from the SEFs.

RESULTS

Primarily tangential current sources accounted for both SEP and SEF distributions at around 20 ms (N20/N20m) and 70 ms (P70/P70m), which deflections were chosen for comparative analysis. The distances between the locations of the maximum current densities obtained from MNE and the locations of ECDs were on the average 12-13 mm for both deflections and nerves stimulated. In accordance with the somatotopical order of SI, both the MNE and ECD tended to localize median nerve activation more laterally than ulnar nerve activation for the N20/N20m deflection. Simulation experiments further indicated that, with a proper estimate of the source depth and with a good fit of the head model, the MNE can reach a mean accuracy of 5 mm in 0.2-microV root-mean-square noise.

CONCLUSIONS

When compared with previously reported localizations based on dipole modelling of SEPs, it appears that equally accurate localization of S1 can be obtained with the MNE.

CONCLUSIONS

MNE can be used to verify parametric source modelling results. Having a relatively good localization accuracy and requiring minimal assumptions, the MNE may be useful for the localization of poorly known activity distributions and for tracking activity changes between brain areas as a function of time.

Fibroblast growth factors (FGFs) mediate many cell-to-cell signaling events during early development. Nou-darake (ndk), a gene encoding an FGF receptor (FGFR)-like molecule, was found to be highly and specifically expressed in the head region of the planarian Dugesia japonica, and its functional analyses provided strong molecular evidence for the existence of a brain-inducing circuit based on the FGF signaling pathway. To analyze the role of ndk during vertebrate development, we isolated the Xenopus ortholog of ndk, the vertebrate FGFR-like 1 gene (XFGFRL1). Expression of XFGFRL1/Xndk was first detected in the anterior region at the late gastrula stage and dramatically increased at the early neurula stage in an overall anterior mesendodermal region, including the prechordal plate, paraxial mesoderm, anterior endoderm, and archenteron roof. This anterior expression pattern resembles that of ndk in planarians, suggesting that the expression of FGFRL1/ndk is conserved in evolution between these two distantly diverged organisms. During the tail bud stages, XFGFRL1/Xndk expression was detected in multiple regions, including the forebrain, eyes, midbrain-hindbrain boundary, otic vesicles, visceral arches, and somites. In many of these regions, XFGFRL1/Xndk was coexpressed with XFGF8, indicating that XFGFRL1/Xndk is a member of the XFGF8 synexpression group, which includes sprouty, sef, and isthmin.

Sclerosing epithelioid fibrosarcoma (SEF) is a recently described entity. It is a low-grade sarcoma that occurs primarily in the deep soft tissues of the extremities of adults. It may histologically simulate benign lesions such as fibroma and myxoma or malignancies such as sclerosing carcinoma and lymphoma, extraskeletal myxoid chondrosarcoma, clear cell sarcoma of tendons and aponeuroses, and synovial sarcoma, depending on the lesion's cellularity, degree of fibrosis, and amount of myxoid matrix. There are no previously published cytogenetic studies of this tumor. We found the karyotype 40-45,XY,add(9)(p13),add(10)(p11),-12,-13,-18,add(18)(q11),add(20)(q11) in a SEF of a 14-year-old boy, by using chromosome banding. Fluorescence in situ hybridization showed that both the add(10) and the add(18) contained amplified sequences from 12q13 and 12q15, including the HMGIC gene. Chromosome 18 material was present in the add(9) and terminally in the add(10). The karyotype of this case indicates that SEF is unrelated to extraskeletal myxoid chondrosarcoma, clear cell sarcoma, and synovial sarcoma. When compared with the findings in other soft tissue tumors such as well-differentiated liposarcoma and low-grade malignant fibrous histiocytoma, the chromosome banding and in situ hybridization data add support to the notion that SEF is a relatively low grade variant of fibrosarcoma.

SEF/IL-17R/CIKS/ACT1 homology (SEFIR) domain containing proteins, which include the IL-17 receptors and an adaptor protein Act1, have essential roles in vertebrate immunity. However, the molecular mechanisms of Act1 function remain largely unexplored. In this article, we employed an evolutionary analysis to discover novel structural and functional properties of Act1. Firstly, we have found that the previously identified helix-loop-helix and Ufd2-box domains in human Act1 have relatively recent evolutionary origins in higher vertebrates. Zebrafish Act1, which lacks these domains, is unable to induce JNK phosphorylation and activate cytokine expression when expressed in human cells. Secondly, we have established that Act1-like proteins contain DEATH-domains in basal animals, such as Hydra and primitive chordates, but lack this domain in vertebrates. Finally, we have shown that Act1-TRAF6 interactions are conserved throughout vertebrate evolution: Act1 derived from zebrafish can bind to TRAF6 and activate NF-κB in human cells. Moreover, we have identified a novel highly conserved motif at the amino-terminus of Act1, which is critical for binding to TRAF6 and activating NF-κB-dependent gene expression. We propose a model of evolutionary changes in Act1-mediated signalling, which contributes to a better understanding of evolution of the vertebrate immunity.

OBJECTIVE

To compare the anaesthetic effects of varying doses of medetomidine (MED) combined with ketamine (KET) in rats, and to determine the efficacy of atipamezole (ATI) in the reversal of these effects using electroencephalogram (EEG) and assessment of clinical parameters.

METHODS

Prospective, randomized experimental trial.

METHODS

Twenty-one male Sprague-Dawley rats weighing 300-398 g and aged 8-11 weeks old.

METHODS

Three groups received intraperitoneal injections of MED (0.2, 0.4 or 0.8 mg kg(-1)) with KET (60 mg kg(-1)) (MED-200, MED-400 and MED-800). Atipamezole, at doses five times higher than the previous dose of MED, was then administered intraperitoneally 70 minutes after MED-KET injection. The EEG band powers and spectral edge frequencies (SEFs), respiratory rates, reflex scores to toe-web clamping and behavioural changes were measured. Correlations between EEG parameters and reflex scores were also evaluated.

RESULTS

The duration of surgical anaesthesia was directly proportional to the dose of MED. Lower frequency bands (delta 1 to alpha2) increased in all groups, and these changes were reversed by ATI. Minimal changes were observed in the higher frequency bands (beta1 to gamma), but their powers were increased by ATI. The SEFs were decreased in all groups, and they were reversed by ATI. While alpha1 band power and SEF95 showed strong correlations with the depth of anaesthesia, their changes appeared before the measured decreases in reflex score. Recovery from anaesthesia was extended by increasing the dose of MED.

CONCLUSIONS

Spectral EEG parameters may not accurately predict the depth of surgical anaesthesia because they had already changed during the induction of surgical anaesthesia. The ATI dose used in the present study may not be enough for complete reversal of anaesthesia induced by MED-KET.

Salmonella enterica serovar Enteritidis is a leading cause of food poisoning in the USA and Europe. Although Salmonella serovars share many fimbrial operons, a few fimbriae are limited to specific Samonella serovars. SEF14 fimbriae are restricted to group D Salmonella and the genes encoding this virulence factor were acquired relatively recently. Genomic, genetic and gene expression studies have been integrated to investigate the ancestry, regulation and expression of the sef genes. Genomic comparisons of the Salmonella serovars sequenced revealed that the sef operon is inserted in leuX in Salmonella Enteritidis, Salmonella Paratyphi and Salmonella Typhi, and revealed the presence of a previously unidentified 25 kb pathogenicity island in Salmonella Typhimurium at this location. Salmonella Enteritidis contains a region of homology between the Salmonella virulence plasmid and the chromosome downstream of the sef operon. The sef operon itself consists of four co-transcribed genes, sefABCD, and adjacent to sefD there is an AraC-like transcriptional activator that is required for expression of the sef genes. Expression of the sef genes was optimal during growth in late exponential phase and was repressed during stationary phase. The regulation was coordinated by the RpoS sigma factor.

BACKGROUND

Visceral leishmaniasis (VL) has been targeted by the WHO for elimination as a public health problem (< 1 case/10,000 people/year) in the Indian sub-continent (ISC) by 2020. Bihar State in India, which accounts for the majority of cases in the ISC, remains a major target for this elimination effort. However, there is considerable spatial, temporal and sub-population variation in occurrence of the disease and the pathway to care, which is largely unexplored and a threat to achieving the target.

METHODS

Data from 6081 suspected VL patients who reported being clinically diagnosed during 2012-2013 across eight districts in Bihar were analysed. Graphical comparisons and Chi-square tests were used to determine differences in the burden of identified cases by season, district, age and sex. Log-linear regression models were fitted to onset (of symptoms)-to-diagnosis and onset-to-treatment waiting times to estimate their associations with age, sex, district and various socio-economic factors (SEFs). Logistic regression models were used to identify factors associated with mortality.

RESULTS

Comparisons of VL caseloads suggested an annual cycle peaking in January-March. A 17-fold variation in the burden of identified cases across districts and under-representation of young children (0-5 years) relative to age-specific populations in Bihar were observed. Women accounted for a significantly lower proportion of the reported cases than men (41 vs 59%, P < 0.0001). Age, district of residence, house wall materials, caste, treatment cost, travelling for diagnosis and the number of treatments for symptoms before diagnosis were identified as correlates of waiting times. Mortality was associated with age, district of residence, onset-to-treatment waiting time, treatment duration, cattle ownership and cost of diagnosis.

CONCLUSIONS

The distribution of VL in Bihar is highly heterogeneous, and reported caseloads and associated mortality vary significantly across different districts, posing different challenges to the elimination campaign. Socio-economic factors are important correlates of these differences, suggesting that elimination will require tailoring to population and sub-population circumstances.

We recorded somatosensory evoked magnetic fields (SEFs) to left median nerve electric stimulation from seven healthy subjects. The stimulus intensity was varied in three sessions: sensory stimuli evoked a clear tactile sensation without any movement, weak motor stimuli exceeded the motor threshold, and strong motor stimuli caused a vigorous movement. Responses were modelled with sources in the contralateral primary somatosensory cortex (SI), the contralateral and ipsilateral secondary somatosensory cortices (SIIs) and the contralateral posterior parietal cortex (PPC). The amplitude of the 20 ms response from the SI cortex and the subjective magnitude estimations followed the stimulus intensity whereas signals from the three other areas saturated already at the level of the motor threshold. The results implicate differential roles for various somatosensory cortices in intensity coding.

Somatostatin receptor type II expression in the mammalian brain displays a spatially and temporally very restricted pattern. In an investigation of the molecular mechanisms controlling these patterns, we have recently shown that binding of the transcription factor SEF-2 to a novel initiator element in the SSTR-2 promoter is essential for SSTR-2 gene expression. Further characterization of the promoter identified a species-conserved TC-rich enhancer element. By screening a mouse brain cDNA expression library, we cloned a cDNA encoding the transcription factor MIBP1. MIBP1 interacts specifically with both the TC box in the SSTR-2 promoter and with the SEF-2 initiator-binding protein to enhance transcription from the basal SSTR-2 promoter. We then investigated SSTR-2, SEF-2, and MIBP1 mRNA expression patterns in the developing and adult murine brain by Northern blotting and in situ hybridization. While SEF-2 is widely expressed in many neuronal and nonneuronal tissues, MIBP1 expression overlapped precisely with expression of SSTR-2 in the frontal cortex and hippocampus. In summary, our data for the first time define a regulatory role for the transcription factor MIBP1 in mediating spatially and temporally regulated SSTR-2 expression in the brain.