Atypical co-development of the thalamus and cortex in autism: Evidence from age-related white-gray contrast change.

Recent studies have shown that white-gray contrast (WGC) of either cortical or subcortical gray matter provides for accurate predictions of age in typically developing (TD) children, and that, at least for the cortex, it changes differently with age in subjects with autism spectrum disorder (ASD) compared to their TD peers. Our previous study showed different patterns of contrast change between ASD and TD in sensorimotor and association cortices. While that study was confined to the cortex, we hypothesized that subcortical structures, particularly the thalamus, were involved in the observed cortical dichotomy between lower and higher processing. The current paper investigates that hypothesis using the WGC measures from the thalamus in addition to those from the cortex. We compared age-related WGC changes in the thalamus to those in the cortex. To capture the simultaneity of this change across the two structures, we devised a metric capturing the co-development of the thalamus and cortex (CoDevTC), proportional to the magnitude of cortical and thalamic age-related WGC change. We calculated this metric for each of the subjects in a large homogeneous sample taken from the Autism Brain Imaging Data Exchange (ABIDE) (N = 434). We used structural MRI data from the largest high-quality cross-sectional sample (NYU) as well as two other large high-quality sites, GU and OHSU, all three using Siemens 3T scanners. We observed that the co-development features in ASD and TD exhibit contrasting patterns; specifically, some higher-order thalamic nuclei, such as the lateral dorsal nucleus, exhibited reduction in codevelopment with most of the cortex in ASD compared to TD. Moreover, this difference in the CoDevTC pattern correlates with a number of behavioral measures across multiple cognitive and physiological domains. The results support previous notions of altered connectivity in autism, but add more specific evidence about the heterogeneity in thalamocortical development that elucidates the mechanisms underlying the clinical features of ASD.

A surface-in gradient of thalamic damage evolves in pediatric multiple sclerosis.

OBJECTIVE: Central nervous system pathology in multiple sclerosis includes both focal inflammatory perivascular injury and injury to superficial structures, including the subpial region of the cortex, which reportedly exhibits a gradient of damage from the surface inward. We assessed how early in the multiple sclerosis course a "surface-in" process of injury suggesting progressive biology may begin. METHODS: We focused on the thalamus, which notably has both a cerebrospinal fluid (CSF) interface and a white matter interface. Thalamic volume trajectories were assessed in a prospectively followed cohort of children from initial presentation with either multiple sclerosis or monophasic acquired demyelination, and healthy controls. Voxelwise volume changes were calculated using deformation-based morphometry, and analyzed in relation to distance from the CSF interface by mixed effects modeling and semiparametric smoothing methods. RESULTS: Twenty-seven children with multiple sclerosis and 73 children with monophasic demyelination were prospectively followed with yearly brain scans (mean follow-up = 4.6 years, standard deviation = 1.9). A total of 282 healthy children with serial scans were included as controls. Relative to healthy controls, children with multiple sclerosis and children with monophasic demyelination demonstrated volume loss in thalamic regions adjacent to the white matter. However, only children with multiple sclerosis exhibited an additional surface-in gradient of thalamic injury on the ventricular side, which was already notable in the first year of clinical disease (asymptote estimate = 3.01, 95% confidence interval [CI] = 1.44-4.58, p = 0.0002) and worsened over time (asymptote:time estimate = 0.33, 95% CI = 0.12-0.54, p = 0.0021). INTERPRETATION: Our results suggest that a multiple sclerosis disease-specific surface-in process of damage can manifest at the earliest stages of the disease. ANN NEUROL 2019;85:340-351.

Evidence for exposure to selenium by breeding interior snowy plovers (Charadrius nivosus) in saline systems of the Southern Great Plains.

Interior snowy plover (Charadrius nivosus) population declines and deteriorating conditions throughout the Southern Great Plains (SGP) of Texas, New Mexico, and Oklahoma may be linked to environmental contaminants. Concentrations of V, As, Cd, Pb, and Se were quantified in breeding snowy plover blood, feathers (5th primary; P5), and potential prey (tiger beetles [Cicindela circumpicta and C. togata]). Se was (a) most commonly detected relative to other quantified elements and (b) frequently quantified at levels exceeding background or toxicity thresholds. Of samples greater than instrumentation detection limits, 98% of snowy plover blood and 22% of feather samples were greater than Se toxicity thresholds of 1 ppm ww for blood and 5 ppm dw for feathers (blood quantifiable range: 0.83-15.12 ppm; feathers quantifiable range: 1.90-27.47 ppm). Almost all tiger beetle Se concentrations were below reported invertebrate thresholds of 30 ppm dw (quantifiable range: 0.54-45.84 ppm). Snowy plover blood Se concentrations were related to sex, individual body condition, and local tiger beetle Se concentrations, while plover P5 Se concentrations were related to state, sex, and presence of body molt. Tiger beetle Se concentrations were related to individual study sites in Texas. These results provide some of the first evidence of Se exposure risk for interior snowy plovers nesting in saline lake and alkali flat environments of the SGP. Future efforts should focus upon specific Se uptake pathways during breeding and nonbreeding seasons, as snowy plovers breeding in the SGP appear to be exposed to Se throughout their annual cycle.

Afferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells.

Appropriate integration of GABAergic interneurons into nascent cortical circuits is critical for ensuring normal information processing within the brain. Network and cognitive deficits associated with neurological disorders, such as schizophrenia, that result from NMDA receptor-hypofunction have been mainly attributed to dysfunction of parvalbumin-expressing interneurons that paradoxically express low levels of synaptic NMDA receptors. Here, we reveal that throughout postnatal development, thalamic, and entorhinal cortical inputs onto hippocampal neurogliaform cells are characterized by a large NMDA receptor-mediated component. This NMDA receptor-signaling is prerequisite for developmental programs ultimately responsible for the appropriate long-range AMPAR-mediated recruitment of neurogliaform cells. In contrast, AMPAR-mediated input at local Schaffer-collateral synapses on neurogliaform cells remains normal following NMDA receptor-ablation. These afferent specific deficits potentially impact neurogliaform cell mediated inhibition within the hippocampus and our findings reveal circuit loci implicating this relatively understudied interneuron subtype in the etiology of neurodevelopmental disorders characterized by NMDA receptor-hypofunction.Proper brain function depends on the correct assembly of excitatory and inhibitory neurons into neural circuits. Here the authors show that during early postnatal development in mice, NMDAR signaling via activity of long-range synaptic inputs onto neurogliaform cells is required for their appropriate integration into the hippocampal circuitry.

The impact of outpatient systemic anti-cancer treatment on patient costs and work practices.

BACKGROUND: There is extensive focus on the rising costs of healthcare. However, for patients undergoing cancer treatment, there are additional personal costs, which are poorly characterised. AIM: To qualify indirect costs during anti-cancer therapy in a designated Irish cancer centre. METHODS: An anonymous questionnaire collected demographic data, current work practice, and personal expenditure on regular and non-regular indirect costs during treatment. Differences between groups of interest were compared using the Mann-Whitney U test. RESULTS: In total, there were 151 responders of median age 58 years; 60 % were female and 74 % were not working. Breast cancer (29 %) was the most frequent diagnosis. Indirect costs totalled a median of €1138 (range €21.60-€7089.84) per patient, with median monthly outgoings of €354. The greatest median monthly costs were hair accessories (€400), transportation (€65), and complementary therapies (€55). The majority (74 %) of patients used a car and median monthly fuel expenditure was €31 (range €1.44-€463.32). Women spent more money during treatment (€1617) than men (€974, p = 0.00128). In addition, median monthly expenditure was greater for those less than 50 years old (€1621 vs €1105; p = 0.04236), those who lived greater than 25 km away (€2015 vs €1078; p = 0.00008) and those without a medical card (€2023 vs €961; p = 0.00024). CONCLUSION: This study highlights the need for greater awareness of indirect expenditures associated with systemic anti-cancer therapy in Ireland.

Eyewitness recall and suggestibility in individuals with Down syndrome.

BACKGROUND: Many criminal justice professionals perceive the eyewitness skills of individuals with intellectual disabilities to be weaker than those of typically developing (TD) individuals. Down syndrome (DS) is one of the most common genetic causes of intellectual disabilities, yet there is no research addressing eyewitness skills in this population. This study examined the eyewitness recall and suggestibility of young people with DS. METHOD: Young people with DS and mental age-matched TD children viewed a video of a non-violent petty crime and were subsequently asked to freely recall the event before being asked general and specific questions incorporating both misleading and non-leading prompts. RESULTS: Compared with mental age-matched TD individuals, young people with DS produced as much information, were just as accurate and were no more suggestible. CONCLUSIONS: The eyewitness memory skills of young people with DS are comparable to those of mental age-matched TD children. The implications of these findings for the forensic context and eyewitness memory are discussed.

Primary screen for potential sheep scab control agents.

The efficacy of potential acaricidal agents were assessed against the sheep scab mite Psoroptes ovis using a series of in vitro assays in modified test arenas designed initially to maintain P. ovis off-host. The mortality effects of 45 control agents, including essential oils, detergents, desiccants, growth regulators, lipid synthesis inhibitors, nerve action/energy metabolism disruptors and ecdysteroids were assessed against adults and nymphs. The most effective candidates were the desiccants (diatomaceous earth, nanoclay and sorex), the growth regulators (buprofezin, hexythiazox and teflubenzuron), the lipid synthesis inhibitors (spirodiclofen, spirotetramat and spiromesifen) and the nerve action and energy metabolism inhibitors (fenpyroximate, spinosad, tolfenpyrad, and chlorantraniliprole).

Assessing the risk of central post-stroke pain of thalamic origin by lesion mapping.

Central post-stroke pain of thalamic origin is an extremely distressing and often refractory disorder. There are no well-established predictors for pain development after thalamic stroke, and the role of different thalamic nuclei is unclear. Here, we used structural magnetic resonance imaging to identify the thalamic nuclei, specifically implicated in the generation of central post-stroke pain of thalamic origin. Lesions of 10 patients with central post-stroke pain of thalamic origin and 10 control patients with thalamic strokes without pain were identified as volumes of interest on magnetic resonance imaging data. Non-linear deformations were estimated to match each image with a high-resolution template and were applied to each volume of interest. By using a digital atlas of the thalamus, we elucidated the involvement of different nuclei with respect to each lesion. Patient and control volumes of interest were summed separately to identify unique areas of involvement. Voxelwise odds ratio maps were calculated to localize the anatomical site where lesions put patients at risk of developing central post-stroke pain of thalamic origin. In the patients with pain, mainly lateral and posterior thalamic nuclei were affected, whereas a more anterior-medial lesion pattern was evident in the controls. The lesions of 9 of 10 pain patients overlapped at the border of the ventral posterior nucleus and the pulvinar, coinciding with the ventrocaudalis portae nucleus. The lesions of this area showed an odds ratio of 81 in favour of developing thalamic pain. The high odds ratio at the ventral posterior nucleus-pulvinar border zone indicates that this area is crucial in the pathogenesis of thalamic pain and demonstrates the feasibility of identifying patients at risk of developing central post-stroke pain of thalamic origin early after thalamic insults. This provides a basis for pre-emptive treatment studies.

The effects of wide pulse neuromuscular electrical stimulation on elbow flexion torque in individuals with chronic hemiparetic stroke.

OBJECTIVE: Neuromuscular electrical stimulation that incorporates wide pulse widths (1ms) and high frequencies (100Hz; wide pulse-NMES (WP-NMES)) augments contractions through an increased reflexive recruitment of motoneurons in individuals without neurological impairments and those with spinal cord injury. The current study was designed to investigate whether WP-NMES also augments contractions after stroke. We hypothesized that WP-NMES would generate larger contractions in the paretic arm compared to the non-paretic arm due to increased reflex excitability for paretic muscles after stroke. METHODS: The biceps brachii muscles were stimulated bilaterally in 10 individuals with chronic hemiparetic stroke. Four stimulation patterns were delivered to explore the effects of pulse width and frequency on contraction amplitude: 20-100-20Hz (4s each phase, 1ms pulse width); 20-100-20Hz (4s each phase, 0.1ms); 20Hz for 12s (1ms); and 100Hz for 12s (1ms). Elbow flexion torque and electromyography were recorded. RESULTS: Stimulation that incorporated 1ms pulses evoked more torque in the paretic arm than the non-paretic arm. When 0.1ms pulses were used there was no difference in torque between arms. For both arms, torque declined significantly during the constant frequency 100Hz stimulation and did not change during the constant frequency 20Hz stimulation. CONCLUSIONS: The larger contractions generated by WP-NMES are likely due to increased reflexive recruitment of motoneurons, resulting from increased reflex excitability on the paretic side. SIGNIFICANCE: NMES that elicits larger contractions may allow for development of more effective stroke rehabilitation paradigms and functional neural prostheses.

MRI correlates of cognitive impairment in childhood-onset multiple sclerosis.

OBJECTIVE: Brain MRI measures were correlated with neuropsychological function in 35 pediatric-onset multiple sclerosis (MS) patients and 33 age- and sex-matched healthy controls. METHOD: Mean age of MS patients was 16.3 ± 2.3 years with average disease duration of 4.3 ± 3.1 years. Cortical gray matter, thalamic, and global brain volumes were calculated for all participants using a scaling factor computed using normalization of atrophy method to normalize total and regional brain volumes for head size. T1- and T2-weighted lesion volumes were calculated for MS patients. RESULTS: Cognitive impairment (CI) was identified in 29% of the MS cohort. Cognitive deficits predominantly involved attention and processing speed, expressive language, and visuomotor integration. Relative to controls, the MS group showed significantly lower thalamic volume (p < .001), total brain volume (p < .008), and gray matter volume (p < .015). Corpus callosum area and thalamic volume differentiated patients identified as having CI from those without CI (p < .05). Regression models controlling for disease duration and age indicated that thalamic volume accounted for significant incremental variance in predicting global IQ, processing speed, and expressive vocabulary (ΔR2 ranging from .43 to .60) and was the most robust MRI predictor of cognition relative to other MRI metrics. CONCLUSIONS: The robust association between cognitive function and reduced size of thalamus and global brain volume in pediatric-onset MS patients implicate neurodegenerative processes early in the disease course, and suggest that plasticity of an immature central nervous system is not sufficient to protect patients from the deleterious consequences of MS on cognitive neural networks. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

Rapid effects of phytoestrogens on human colonic smooth muscle are mediated by oestrogen receptor beta.

Epidemiological studies have correlated consumption of dietary phytoestrogens with beneficial effects on colon, breast and prostate cancers. Genomic and non-genomic mechanisms are responsible for anti-carcinogenic effects but, until now, the effect on human colon was assumed to be passive and remote. No direct effect on human colonic smooth muscle has previously been described. Institutional research board approval was granted. Histologically normal colon was obtained from the proximal resection margin of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended under 1g of tension in organ baths containing oxygenated Krebs solution at 37 degrees C. After an equilibration period, tissues were exposed to diarylpropionitrile (DPN) (ER beta agonist) and 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) (ER alpha agonist) or to the synthetic phytoestrogen compounds genistein (n=8), daidzein (n=8), fisetin (n=8) and quercetin (n=8) in the presence or absence of fulvestrant (oestrogen receptor antagonist). Mechanism of action was investigated by inhibition of downstream pathways. The cholinergic agonist carbachol was used to induce contractile activity. Tension was recorded isometrically. Phytoestrogens inhibit carbachol-induced colonic contractility. In keeping with a non-genomic, rapid onset direct action, the effect was within minutes, reversible and similar to previously described actions of 17 beta oestradiol. No effect was seen in the presence of fulvestrant indicating receptor modulation. While the DPN exerted inhibitory effects, PPT did not. The effect appears to be reliant on a p38/mitogen activated protein kinase mediated induction of nitric oxide production in colonic smooth muscle. The present data set provides the first description of a direct effect of genistein, daidzein, fisetin and quercetin on human colonic smooth muscle. The presence of ER in colonic smooth muscle has been functionally proven and the beta isoform appears to play a predominant role in exerting non-genomic effects.

Design, construction, and validation of an MRI-compatible vibrotactile stimulator intended for clinical use.

Vibrotactile stimulation has been used successfully to activate the human somatosensory pathway in functional magnetic resonance imaging (fMRI) experiments. The design and characterization of these devices are of particular interest in frequency discrimination tasks and investigations of the somatopic organization of sensory areas. However, few have investigated the utility of vibrotactile stimulation in a clinical context. We have previously demonstrated that vibrotactile stimulation can provide robust activations in areas targeted in stereotactic functional neurosurgical procedures used for tumour resection (i.e.: primary and secondary somatosensory areas) and subcortical targets for thalamic pain and movement disorders (i.e.: sensory thalamus). The main contribution of this manuscript is the presentation of the design, materials, construction, and validation of a novel vibrotactile stimulator intended for clinical use. The thalamic activations are also compared to a digital atlas in order to evaluate anatomical localization. The proposed stimulator was constructed entirely from non-ferromagnetic parts, uses compressed air to deliver stimulation using computer control, and stimulates the entirety of the hand and fingers to ensure robust somatosensory activations. In addition, this stimulator is constructed entirely from "off-the-shelf" parts and would be easily replicated due to the simplicity of design and the relatively small expense of the parts required. The device was tested by stimulating the right hand of 10 normal controls (5 females, 5 males, all right handed; age range: 25-42 years, mean: 30.9 years, standard deviation: 5.2 years) during an fMRI experiment. The results demonstrate significant single subject activations of primary and secondary somatosensory cortices and of the sensory thalamus.

Comparison of piece-wise linear, linear, and nonlinear atlas-to-patient warping techniques: analysis of the labeling of subcortical nuclei for functional neurosurgical applications.

Digital atlases are commonly used in pre-operative planning in functional neurosurgical procedures performed to minimize the symptoms of Parkinson's disease. These atlases can be customized to fit an individual patient's anatomy through atlas-to-patient warping procedures. Once fitted to pre-operative magnetic resonance imaging (MRI) data, the customized atlas can be used to plan and navigate surgical procedures. Linear, piece-wise linear and nonlinear registration methods have been used to customize different digital atlases with varying accuracies. Our goal was to evaluate eight different registration methods for atlas-to-patient customization of a new digital atlas of the basal ganglia and thalamus to demonstrate the value of nonlinear registration for automated atlas-based subcortical target identification in functional neurosurgery. In this work, we evaluate the accuracy of two automated linear techniques, two piece-wise linear techniques (requiring the identification of manually placed anatomical landmarks), and four different automated nonlinear atlas-to-patient warping techniques (where two of the four nonlinear techniques are variants of the ANIMAL algorithm). Since a gold standard of the subcortical anatomy is not available, manual segmentations of the striatum, globus pallidus, and thalamus are used to derive a silver standard for evaluation. Four different metrics, including the kappa statistic, the mean distance between the surfaces, the maximum distance between surfaces, and the total structure volume are used to compare the warping techniques. The results show that nonlinear techniques perform statistically better than linear and piece-wise linear techniques. In addition, the results demonstrate statistically significant differences between the nonlinear techniques, with the ANIMAL algorithm yielding better results.

Robust S1, S2, and thalamic activations in individual subjects with vibrotactile stimulation at 1.5 and 3.0 T.

Functional magnetic resonance imaging (fMRI) is often used to enhance visualization and provide target localization during the planning phase of neurosurgical procedures. Although parametric maps have been used to identify areas of eloquent cortex such as the primary (S1) and secondary (S2) somatosensory areas for tumor surgery, to date, few fMRI methods exist to localize subcortical targets for surgical interventions used to treat movement disorders. The scanning time required to obtain statistically significant functional signals must be balanced against the possibility of movement artifacts and patient discomfort. We propose a vibrotactile stimulation technique to activate the somatosensory pathway for neurosurgical planning and perform a sensitivity analysis to determine the amount of time required to achieve significant activations of S1, S2, and sensory thalamus in individual subjects. Bilateral stimulation experiments were carried out on two MRI scanners (n = 13 at 1.5 T; n = 5 at 3.0 T). The analysis demonstrates that statistically significant functional activations can be achieved in clinically acceptable times: 16 min at 1.5 T (26/26 experiments) and 6 min at 3.0 T (10/10) for S1 activations; 24 min at 1.5 T (22/26) and 18 min at 3.0 T for S2 activations (9/10); and 32 min at 1.5 T (15/26) and 18 min at 3.0 T (10/10) for activation of thalamic nuclei. These results demonstrate that S1 and S2 activations are robust at 1.5 and 3.0 T, and that robust thalamic activations in individual subjects are possible at 3.0 T. These techniques demonstrate that this technique can be used for preoperative planning for surgical candidates.

Focal gray matter changes in schizophrenia across the course of the illness: a 5-year follow-up study.

Recent volumetric magnetic resonance imaging (MRI) studies have suggested brain volume changes in schizophrenia to be progressive in nature. Whether this is a global process or some brain areas are more affected than others is not known. In a 5-year longitudinal study, MRI whole brain scans were obtained from 96 patients with schizophrenia and 113 matched healthy comparison subjects. Changes over time in focal gray and white matter were measured with voxel-based morphometry throughout the brain. Over the 5-year interval, excessive decreases in gray matter density were found in patients in the left superior frontal area (Brodmann areas 9/10), left superior temporal gyrus (Brodmann area 42), right caudate nucleus, and right thalamus as compared to healthy individuals. Excessive gray matter density decrease in the superior frontal gray matter was related to increased number of hospitalizations, whereas a higher cumulative dose of clozapine and olanzapine during the scan interval was related to lesser decreases in this area. In conclusion, gray matter density loss occurs across the course of the illness in schizophrenia, predominantly in left frontal and temporal cortices. Moreover, the progression in left frontal density loss appears to be related to an increased number of psychotic episodes, with atypical antipsychotic medication attenuating these changes.

Blood transfusion requirement prediction in patients undergoing primary total hip and knee arthroplasty.

The aim of this study was to identify the clinical factors associated with the need for peri-operative blood transfusion in non-anaemic patients undergoing hip or knee arthroplasty. We prospectively evaluated 162 consecutive patients who underwent total hip or knee arthroplasty. Analysis was performed to establish the relationship between all independent variables and the need for postoperative transfusion. Univariate analysis revealed a significant relationship between the need for postoperative blood transfusion and the pre-operative haemoglobin levels (P= 0.001), weight (P= 0.019) and age (P= 0.018). Multivariate analysis identified a significant relationship only between the need for transfusion and the pre-operative haemoglobin level (P= 0.0001). The pre-operative haemoglobin level of the patient was the only variable to independently predict the need for blood transfusion after primary hip or knee arthroplasty.

The penitentiary visit--a new role for geriatricians?

The number of older prisoners is increasing and, with reforms in the prison health service, there is a requirement to provide equity of access to standard healthcare services. The health of older prisoners is often poor, with high levels of psychiatric and physical illnesses, compounded by poor access to appropriate rehabilitation and resettlement services. A recent case presenting to our department highlighted these deficits and illustrated how inputs from a geriatrician could be useful to older prisoners (see Appendix 1, available at www.ageing.oxfordjournals.org). We propose that regular penitentiary visits may be an important new role for geriatricians at a supra-regional level.

The creation of a brain atlas for image guided neurosurgery using serial histological data.

Digital and print brain atlases have been used with success to help in the planning of neurosurgical interventions. In this paper, a technique presented for the creation of a brain atlas of the basal ganglia and the thalamus derived from serial histological data. Photographs of coronal histological sections were digitized and anatomical structures were manually segmented. A slice-to-slice nonlinear registration technique was used to correct for spatial distortions introduced into the histological data set at the time of acquisition. Since the histological data were acquired without any anatomical reference (e.g., block-face imaging, post-mortem MRI), this registration technique was optimized to use an error metric which calculates a nonlinear transformation minimizing the mean distance between the segmented contours between adjacent pairs of slices in the data set. A voxel-by-voxel intensity correction field was also estimated for each slice to correct for lighting and staining inhomogeneity. The reconstructed three-dimensional (3D) histological volume can be viewed in transverse and sagittal directions in addition to the original coronal. Nonlinear transformations used to correct for spatial distortions of the histological data were applied to the segmented structure contours. These contours were then tessellated to create three-dimensional geometric objects representing the different anatomic regions in register with the histological volumes. This yields two alternate representations (one histological and one geometric) of the atlas. To register the atlas to a standard reference MR volume created from the average of 27 T1-weighted MR volumes, a pseudo-MRI was created by setting the intensity of each anatomical region defined in the geometric atlas to match the intensity of the corresponding region of the reference MR volume. This allowed the estimation of a 3D nonlinear transformation using a correlation based registration scheme to fit the atlas to the reference MRI. The result of this procedure is a contiguous 3D histological volume, a set of 3D objects defining the basal ganglia and thalamus, both of which are registered to a standard MRI data set, for use for neurosurgical planning.

The effect of active immunization against adrenocorticotropic hormone on cortisol, beta-endorphin, vocalization, and growth in pigs.

Because the poor growth performance of intensively housed pigs is associated with increased circulating glucocorticoid concentrations, we investigated the effects of glucocorticoid suppression by inducing a humoral immune response to ACTH on physiological and production variables in growing pigs. Grower pigs (28.6 +/- 0.9 kg) were immunized with amino acids 1 through 24 of ACTH conjugated to ovalbumin and suspended in diethylaminoethyl (DEAE) dextran-adjuvant or adjuvant alone (control) on d 1, 28, and 56. The ACTH-specific antibody titers generated suppressed increases in cortisol concentrations on d 63 in response to an acute stressor (P = 0.002; control = 71 +/- 8.2 ng/mL; ACTH-immune = 43 +/- 4.9 ng/mL) without altering basal concentrations. Plasma beta-endorphin concentrations were also increased (P < 0.001) on d 63 (control = 18 +/- 2.1 ng/mL; ACTH-immune = 63 +/- 7.3 ng/mL), presumably because of a release from negative feedback on the expression of proopiomelanocortin in pituitary corticotropes. Immunization against ACTH did not alter ADG (P = 0.120; control = 1,077 +/- 25; ACTH-immune = 1,143 +/- 25 g) or ADFI (P = 0.64; control = 2,719 +/- 42; ACTH-immune = 2,749 +/- 42 g) and did not modify behavior (P = 0.681) assessed by measuring vocalization in response to acute restraint. In summary, suppression of stress-induced cortisol responses through ACTH immunization increased beta-endorphin concentrations, but it did not modify ADG, ADFI, or restraint vocalization score in growing pigs.

In vitro evaluation of concurrent use of commercially available insect repellent and sunscreen preparations.

BACKGROUND: Insect repellents and sunscreens are over-the-counter products extensively used by the general public. Concurrent application of these products has become widespread in many regions across North America, because of concerns about West Nile virus and skin cancers. OBJECTIVES: We investigated whether formulation type, application amount, and sequence would affect the percutaneous absorption profiles of the active repellent and sunscreen ingredients. METHODS: In vitro percutaneous permeation of the repellent N,N-diethyl-m-toluamide (DEET) and the sunscreen oxybenzone from concurrent application of five commercially available products (A, repellent spray; B, repellent lotion; C, sunscreen lotion; D and E, combined repellent/sunscreen lotions) was measured and compared using Franz-style diffusion cells with piglet skin at 37 degrees C. RESULTS: Penetration of DEET in A and B increased by 1640% and 282%, respectively, when C was applied concurrently. Penetration of DEET in D and E was 53% and 79% higher than that in B. Permeation of DEET from A + C (2:1) and A + C (1: 2) increased by 530% and 278%, respectively. Permeation of oxybenzone was 189% and 280% higher in A + C and B + C than in C. Permeation of oxybenzone in D and E was also 221% and 296% higher than that in C. Permeation of oxybenzone was 196% greater when A was applied on top of C than when C was applied on top of A, while oxybenzone in A + C (1:2) permeated 171% more than that in A + C (2:1). CONCLUSIONS: Concurrent application of commercially available repellent and sunscreen products resulted in significant synergistic percutaneous permeation of the repellent DEET and the sunscreen oxybenzone in vitro. The percutaneous penetration profiles were dependent upon the type of formulation, application sequence and application proportion.