Gray matter brain structures, including deep nuclei and the cerebral cortex, are affected significantly and early in the course of multiple sclerosis and these changes may not be directly related to ...demyelinating white matter lesions. The hippocampus is an archicortical structure that is critical for memory functions and is especially sensitive to multiple insults including inflammation. We used high-resolution MR imaging at 3.0 T to measure hippocampal volumes in relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) patients and controls. We found that both groups of MS patients had hippocampal atrophy and that this volume loss was in excess of global brain atrophy. Subregional analysis revealed selective volume loss in the cornu ammonis (CA) 1 region of the hippocampus in RRMS with further worsening of CA1 loss and extension into other CA regions in SPMS. Hippocampal atrophy was not correlated with T2-lesion volumes, and right and left hippocampi were affected equally. Volume loss in the hippocampus and subregions was correlated with worsening performance on word-list learning, a task requiring memory encoding, but not with performance on the Paced Auditory Serial Addition Task (PASAT), a test of information processing speed. Our findings provide evidence for selective and progressive hippocampal atrophy in MS localized initially to the CA1 subregion that is associated with deficits in memory encoding and retrieval. The underlying histopathological substrate for this selective, symmetric and disproportionate regional hippocampal vulnerability remains speculative at this time. Further understanding of this process could provide targets for therapeutic interventions including neuroprotective treatments.
Background: Hippocampal atrophy preferentially affects the CA1 region in early multiple sclerosis (MS). Volume loss, especially in the left hippocampus, is correlated with deficits in verbal ...learning. The spatial localization and extent of hippocampal volume change in MS in association with clinical variables has not been characterized. Objective: To localize hippocampal atrophy in MS patients compared with controls using a three-dimensional surface displacement mapping technique, and to determine if these changes are correlated with clinical measures. Methods: The right and left hippocampi (CA1-3, dentate gyrus and subiculum) were manually segmented from a standard T1-weighted scan obtained at 1.5 T (resolution 1 mm3) by a single trained researcher. A total of 23 relapsing- remitting MS (RRMS) patients and 18 controls were studied. Using a previously described high resolution surface mesh algorithm, average surface maps were generated for controls and RRMS patients. Differences in surface landmarks between the groups were determined over the entire left and right hippocampus. Significance of detected displacements was determined using the Wilcoxon ranked-sum test adjusted for multiple comparisons with the permutation test. The relationship of clinical variables (performance on an unrelated word list learning task, PASAT performance and T2 lesion volume measures) was assessed using linear regression. Results: Surface displacements in the RRMS patients were greater in the anterior hippocampal region and statistically significant displacement was detectable in the left anterior subiculum. Surface displacement was greater for the left versus the right hippocampus. Worsening verbal learning performance was correlated with greater displacement in the left anterior CA regions, while PASAT performance and T2 lesion volumes were not correlated with regional hippocampal changes. Conclusions: Changes in hippocampal volumes in RRMS are localized to anterior regions as revealed by three-dimensional surface mapping. Left anterior hippocampal changes are associated with deficits in verbal learning but not T2 lesion volumes. The hippocampus is vulnerable to clinically relevant changes in MS.
Background: Multiple sclerosis (MS) patients experience a wide spectrum of cognitive deficits, and verbal memory deficits are common. Verbal encoding is dependent on the medial temporal lobe (MTL) ...and the hippocampus. Previous functional magnetic resonance imaging (fMRI) studies show that in normal learning, encoding activates the anterior CA1-3 and dentate gyrus (antCADG) regions of the hippocampus. We recently demonstrated reductions in hippocampal gray matter volume localized to the CA1 subregion in early MS patients and significant loss in all hippocampal regions in secondary progressive patients. Objective: To assess whether alterations in hippocampal functional activity are present in MS, and if they contribute to verbal memory deficits, fMRI and a novel cortical unfolding technique were used to investigate BOLD signal differences in specific subregions of the hippocampus and MTL during a verbal memory task. Methods: High-resolution structural and functional MRls were acquired for each subject at 3.0T. An unrelated word-pairs test was used to determine verbal memory performance. Cortical unfolding of the hippocampus and nearby MTL was performed using a previously described technique. After interpolation, flattened templates had an isotropic resolution of 0.4 mm and demarcated 10 specific subregions. Significant group activations, corrected for multiple comparisons, were then overlaid on combined group templates to show subreglon-specific activity during encoding and recall. Results: During the task, patients required more trials than controls to learn all word pairs. Controls showed activations specific to the antCADG during encoding, consistent with previous literature. Patients did not show this same pattern, but instead showed extra-hippocampal activity localized to the perirhinal cortex. Conclusions: While MS affects hippocampal volume, it is unknown how these structural changes contribute to verbal memory deficits. Using fMRI, we find that MS patients deviate from normal activation patterns in the antCADG region during encoding. Patients instead demonstrate greater activity in the perirhinal cortex, a region that inputs into the hippocampus via the entorhinal cortex. These differences may account for verbal memory deficits.
•Dermatomyositis is an autoimmune inflammatory myopathy with cutaneous symptoms.•We review the literature to provide an update on the pathogenesis of the disease.•Type I interferons and associated ...genes and proteins appear to influence disease.•Autoantibodies and other cytokines also appear to affect disease activity.•Further studies are indicated to improve understanding and therapeutic strategies.
Much work has been done to unveil the mechanisms behind the pathogenesis of dermatomyositis (DM) – mainly those involving certain pathogenic cytokines, termed “pathokines” as the principal cytokines involved. Recently, it has become clear that a group of cytokines known as type I interferons (IFN-Is) play a significant role in the development of DM. We review the literature published between 1946 and 2014 using an Ovid Medline database search to provide an update on the role of IFN-Is and other cytokines in the pathogenesis of DM. We provide information about the genes and proteins induced by IFN-Is and potential mechanisms by which these downstream products relate to clinical disease activity. We also explore findings of other autoimmune phenomena that may contribute to disease onset and activity including T-helper 17 (Th17) cells and associated interleukins, as well as autoantibodies. Finally, we provide a brief update on current treatment options for DM as well as some new immunomodulatory treatment modalities in development.
Since dermatologists routinely perform surgery in an outpatient setting, ensuring that dermatology trainees are provided with opportunities to develop sufficient proficiency in excisional surgery and ...suture technique is paramount. The objectives of this study are to assess trainee preference for silicone-based synthetic skin compared with porcine skin as a surgical training medium and to assess the ability of trainees to successfully demonstrate basic surgical skills using the simulated skin model. Participants were a convenience sample of dermatology residents from the greater Chicago area, who were asked to perform an elliptical excision and bilayered repair on a silicone-based synthetic skin model. Residents were then surveyed regarding their satisfaction with the model. Four blinded dermatologist raters evaluated digital photographs obtained during the performance of the procedures and graded the execution of each maneuver using a surgical task checklist. Nineteen residents were enrolled. Residents were more likely to prefer pig skin to simulated skin for overall use (
p
= 0.040) and tissue repair (
p
= 0.018), but the nominal preference for tissue handling was nonsignificant (
p
= 0.086). There was no significant difference between satisfaction with pig skin versus synthetic skin with regard to excision experience (
p
= 0.82). The majority of residents (10/19) performed all surgical checklist tasks correctly. Of those residents who did not perform all steps correctly, many had difficulty obtaining adequate dermal eversion and wound approximation. Synthetic skin may be conveniently and safely utilized for hands-on surgical practice. Further refinement may be necessary to make synthetic skin comparable in feel and use to animal skin.
The reasons for hiring military veterans/reservists are well documented, including such factors as leadership, teamwork, and resilience. Research shows that veterans/reservists perform at higher ...levels, have lower turnover rates after the first job, and advance more rapidly in Federal civil service organizations. However, the impact of hiring veterans/reservists on a firm’s financial performance remains unexplored. Using GI Job’s list of “2016 Top 100 Military Friendly Firms,” we demonstrate that the 64 publicly traded “military friendly” firms on this list had a statistically significant higher return (median 7.23 percentage points and a mean 5.18 percentage points higher) than comparable firms not identified as military friendly. These findings provide compelling evidence of the financial benefits associated with employing military veterans/reservists in response to the call for more empirical research on the impact of veterans in civilian organizations. In addition to encouraging businesses to consider hiring veterans/reservists, our results may be beneficial for career counselors, human resource and development managers, and others who interact with veterans, as well as for veterans themselves.
Scarring following skin surgery is an unavoidable certainty. Scars resulting from Mohs Micrographic Surgery (MMS) can cause both cosmetic and functional problems. Various lasers have been used to ...treat scars, but the role of the microsecond pulsed 1064 nanometer neodymium-doped yttrium aluminum garnet (1064 nm Nd:YAG) in treating surgical scars is not well-defined.
We aim to examine the clinical application of the 1064 nm Nd:YAG laser in improving surgical scars.
Ten patients who were unhappy with cosmetic or functional outcomes of their surgical scars following MMS were treated with 1-3 sessions of the 1064 nm Nd:YAG laser to improve their scars. Therapy completion was determined by patient satisfaction with the appearance of their scars and/or resolution of any contractures that formed following surgery.
All ten patients were pleased with the improved appearance of their scars. Four patients saw complete resolution of an ectropion or eclabium that formed secondary to scar contractures from MMS. The side effects of laser treatments were limited to 1-2 hours of erythema, and there were no incidences of adverse effects or recurrence of contractures.
Our clinical experience with the 1064 nm Nd:YAG laser provides promising data on improving appearance of and functionality from post-surgical scars.
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