Hyponatraemia in Guillain-Barré syndrome revisited.

OBJECTIVES: The objective of this study was to determine the relevance of hyponatraemia in the prognosis of Guillain-Barré syndrome (GBS). MATERIALS AND METHODS: We retrospectively analysed records of 48 consecutive patients with GBS and performed a systematic literature review on frequency/correlates of hyponatraemia in GBS. RESULTS: Hyponatraemia <133 mmol/l was detected in 18/48 of our patients with GBS (37.5%). In 10/18 (55.5%), hyponatraemia occurred post-immunoglobulin therapy. Hyponatraemia correlated with age >50 years (P = 0.011), concurrent malignancy (P = 0.039), diuretic use (P < 0.001), preceding diarrhoea (P = 0.042) and Medical Research Council (MRC) sum score at discharge (MRCSSD) (P = 0.026). Only concurrent malignancy (P < 0.001) and diuretic use (P < 0.001) were independently associated with hyponatraemia. MRCSSD also correlated with MRC sum score on admission (MRCSSA) (P < 0.001), length of hospital stay (P < 0.001), summated compound muscle action potential (P = 0.034) and lowest forced vital capacity (P = 0.001). Only MRCSSA (P = 0.004) and length of hospital stay (P < 0.001) independently predicted MRCSSD. Combining our findings with previous literature indicates comparable frequencies of hyponatraemia in GBS in four of five studies and association with mortality in three of four studies, with an independent link in one. Independent association of hyponatraemia with muscle strength is not demonstrated. CONCLUSION: Hyponatraemia appears of comparable frequency in GBS to that in other diseased cohorts suggesting it is common but non-specific. Hyponatraemia has otherwise been shown to be an independent predictor of death in other disorders and available data indicate the same is also likely in GBS, although this may vary in patient subgroups. Hyponatraemia is, however, not an independent prognostic indicator of neuromuscular weakness severity in GBS.

Perceptions and behaviors of learner engagement with virtual educational platforms.

BACKGROUND: The COVID-19 pandemic has increased utilization of educational technology for surgical education. Our aim was to determine attitudes and behaviors of surgical education champions towards virtual educational platforms and learner engagement. METHODS: An electronic survey was distributed to all Association of Surgical Education members addressing i) methods of engagement in virtual learning ii) ways to improve engagement and iii) what influences engagement. Stratified analysis was used to evaluate differences in responses by age, gender, level of training and specialty. RESULTS: 154 ASE members completed the survey (13% response rate). 88% respondents accessed virtual learning events at home. Most (87%) had joined a virtual learning event and then participated in another activity. 1 in 5 who did this did so "always" or "often". Female respondents were more likely than males to join audio and then participate in another activity (62.3% v 37.7%, p = 0.04). CONCLUSIONS: Virtual platforms do not automatically translate into increased learner engagement. Careful design of educational strategies is essential to increase and maintain learner engagement when utilizing virtual surgical education.

Predicting the survival of experimental ischaemic small bowel using intraoperative near-infrared fluorescence angiography.

BACKGROUND: Predicting the long-term viability of ischaemic bowel during surgery is challenging. The aim was to determine whether intraoperative near-infrared angiography (NIR-AG) of ischaemic bowel might provide metrics that were predictive of long-term outcome. METHODS: NIR-AG using indocyanine green was performed on 24 pigs before, and after inducing bowel ischaemia to determine the feasibility of NIR-AG for detecting compromised perfusion. Contrast-to-background ratio (CBR) over time was measured in regions of interest throughout the bowel, and various metrics of the CBR-time curve were developed. Sixty rat small bowels, with or without strangulation, were imaged during surgery and on day 3 after operation. CBR metrics and clinical findings were assessed quantitatively for their ability to predict animal survival, histological grade of ischaemic injury and visible necrosis on day 3. RESULTS: In ischaemic pig small bowel, various qualitative and quantitative CBR metrics appeared to correlate with bowel injury as a function of distance from normal bowel. In rats, intraoperative clinical assessment showed high specificity but low sensitivity for predicting outcome on day 3 after operation. Qualitative patterns of the CBR-time curve, such as absence of an arterial inflow peak and presence of a NIR filling defect, resulted in better prediction of survival (90 per cent), histological grade (85 per cent) and visible necrosis on day 3 (92 per cent). CONCLUSION: Survival of ischaemic bowel was predicted by intraoperative NIR-AG with greater accuracy than clinical evaluation alone.

Assessing learner engagement with virtual educational events: Development of the Virtual In-Class Engagement Measure (VIEM).

BACKGROUND: The COVID-19 pandemic has necessitated virtual education, but effects on learner engagement are unknown. We developed a virtual in-class engagement measure (VIEM) to assess learner engagement in online surgical education events. METHODS: Using the STROBE, an observer collected tool to document student engagement, as a template an ASE committee workgroup developed the VIEM. The VIEM had two parts: observer assessment and learner self-assessment of engagement. Trained observers collected engagement data from two institutions using the VIEM. Surgical attendings, fellows and residents were observed during virtual learning events. Educator attitudes towards online teaching were also assessed via survey. RESULTS: 22 events with 839 learners were observed. VIEM distinguished between sessions with low and high engagement. 20% of learners pretended to participate. Half of instructors were comfortable with virtual teaching, but only 1/3 believed was as effective as in-person. 2/3 of teachers believed video learners were more engaged than audio learners. CONCLUSIONS: Virtual platforms do not automatically translate into increased engagement. Standard tools such as VIEM may help with assessment of engagement during virtual education.

McArdle disease: a clinical review.

METHODS: The clinical phenotype of 45 genetically confirmed McArdle patients is described. RESULTS: In the majority of patients (84%), the onset of symptoms was from early childhood but diagnosis was frequently delayed until after 30 years of age. Not all patients could recognise a second wind although it was always seen with exercise assessment. A history of myoglobinuria was not universal and episodes of acute renal failure had occurred in a minority (11%). The condition does not appear to adversely affect pregnancy and childbirth. Clinical examination was normal in most patients, muscle hypertrophy was present in 24% and mild muscle wasting and weakness were seen only in patients over 40 years of age and was limited to shoulder girdle and axial muscles. The serum creatine kinase was elevated in all but one pregnant patient. Screening for the mutations pArg50X (R50X) and pGly205Ser (G205S) showed at least one mutated allele in 96% of Caucasian British patients, with an allele frequency of 77% for pArg50X in this population. A 12 min walking test to evaluate patients is described. CONCLUSION: The results demonstrated a wide spectrum of severity with the range of distance walked (195-1980 m); the mean distance walked was 512 m, suggesting significant functional impairment in most patients.

Detection of somatic DNA recombination in the transgenic mouse brain.

A DNA construct containing the bacterial beta-galactosidase gene (lacZ) was used to study somatic DNA recombination in the transgenic mouse brain. Recombination-positive areas of the adult brain were stained blue with X-gal, a substrate of beta-galactosidase. Blue-colored cells appeared soon after birth, and continued to emerge in postnatal tissue. Staining was prominent in sensory as opposed to motor regions of the brain, and was present in more than 70 discrete areas of the nervous system. The possibility of DNA rearrangement is discussed with respect to the development of the central nervous system.

When the Guillain-Barre patient fails to respond to treatment.

Most patients with Guillain-Barré syndrome (GBS) respond to treatment with intravenous immunoglobulin, but it is not uncommon for some to continue to deteriorate for a period after treatment has been started. This may reflect the natural history of the disease, or an error in diagnosis. This article reflects my own view of what to do in this situation, with a review of what few data there are to guide decision making.

Computed Tomography of the Mandibles of a Stranded Offshore Killer Whale (Orcinus orca).

A mature, adult female, offshore killer whale (Orcinus orca) was stranded deceased in Portage Bay, Alaska, in October 2015. Full necropsy examination with histopathology was performed. Consistent with previous studies of offshore killer whales, and thought to be a result of their unique elasmobranch diet, all the teeth were significantly abraded and almost flush with the gingival margin. Age was estimated at 30-35 years based on annuli and growth arrest lines in a remaining tooth. The dentate portion of the mandibles were excised en bloc and frozen until imaging could be completed. Radiography and computed tomography revealed lesions consistent with severe abrasion, pulp exposure and evidence of endodontic and/or periodontal disease in nine of the 15 mandibular teeth present (60.0%). Only five (33.3%) teeth were suspected to have been vital at the time of death based on imaging. Lesions were more severe rostrally, with the caudal teeth less affected. Autolysis precluded gingival histopathology and no teeth were analyzed histologically. Necropsy examination revealed a likely multifactorial cause of death, with most significant lesions including the severe chronic periodontal/endodontic disease with abrasion, inanition and emaciation with possible cardiovascular disease. This case highlights the importance of imaging in evaluating periodontal and endodontic status, especially post mortem when other tissues are no longer available, and demonstrates that periodontal and endodontic disease occur naturally in this species and can be a significant cause of morbidity in mature free-ranging killer whales of the offshore ecotype.

Branched projections in the auditory thalamocortical and corticocortical systems.

Branched axons (BAs) projecting to different areas of the brain can create multiple feature-specific maps or synchronize processing in remote targets. We examined the organization of BAs in the cat auditory forebrain using two sensitive retrograde tracers. In one set of experiments (n=4), the tracers were injected into different frequency-matched loci in the primary auditory area (AI) and the anterior auditory field (AAF). In the other set (n=4), we injected primary, non-primary, or limbic cortical areas. After mapped injections, percentages of double-labeled cells (PDLs) in the medial geniculate body (MGB) ranged from 1.4% (ventral division) to 2.8% (rostral pole). In both ipsilateral and contralateral areas AI and AAF, the average PDLs were <1%. In the unmapped cases, the MGB PDLs ranged from 0.6% (ventral division) after insular cortex injections to 6.7% (dorsal division) after temporal cortex injections. Cortical PDLs ranged from 0.1% (ipsilateral AI injections) to 3.7% in the second auditory cortical area (AII) (contralateral AII injections). PDLs within the smaller (minority) projection population were significantly higher than those in the overall population. About 2% of auditory forebrain projection cells have BAs and such cells are organized differently than those in the subcortical auditory system, where BAs can be far more numerous. Forebrain branched projections follow different organizational rules than their unbranched counterparts. Finally, the relatively larger proportion of visual and somatic sensory forebrain BAs suggests modality specific rules for BA organization.

Two thalamic pathways to primary auditory cortex.

Neurons in the center of cat primary auditory cortex (AI) respond to a narrow range of sound frequencies and the preferred frequencies in local neuron clusters are closely aligned in this central narrow bandwidth region (cNB). Response preferences to other input parameters, such as sound intensity and binaural interaction, vary within cNB; however, the source of this variability is unknown. Here we examined whether input to the cNB could arise from multiple, anatomically independent subregions in the ventral nucleus of the medial geniculate body (MGBv). Retrograde tracers injected into cNB labeled discontinuous clusters of neurons in the superior (sMGBv) and inferior (iMGBv) halves of the MGBv. Most labeled neurons were in the sMGBv and their density was greater, iMGBv somata were significantly larger. These findings suggest that cNB projection neurons in superior and iMGBv have distinct anatomic and possibly physiologic organization.

Dental and Temporomandibular Joint Pathology of the Grey Wolf (Canis lupus).

Skulls from 392 grey wolves (Canis lupus) were examined macroscopically according to predefined criteria. Two hundred and seven skulls were included in this study, comprised of 124 young adults (59.9%) and 83 adults (40.1%); of these, 65 (31.4%) specimens were from male wolves and 104 (50.3%) were from females, with 38 (18.4%) of unknown sex. Out of 8,694 possible teeth, 8,339 (95.9%) were present for evaluation. Fifty-five teeth (15.5%) were absent congenitally, 30 (8.5%) were lost during life and 270 (76.1%) were lost artefactually post mortem. Skeletal or dental malocclusion was present in 37 specimens (17.9%), with level bite being the most commonly encountered malocclusion. Enamel hypoplasia was present in five skulls (2.4%), affecting eight teeth (0.1%) in total. An abnormal number of roots was found on 23 teeth (0.3%) on 13 skulls (6.3%). Persistent deciduous teeth occurred in two (1.0%) specimens, affecting one (0.01%) tooth each. Fenestration or dehiscence was found associated with 203 teeth (2.4%) in 72 skulls (34.8%). Periodontitis was noted on 115 skulls (55.6%) and 1,000 teeth (11.5%), affecting significantly more adults (n = 63, 75.0%) than young adults (n = 52, 41.9%; P <0.0001). One hundred and sixty-one skulls (77.8%) showed signs of endodontal disease, including attrition or abrasion on 144 skulls (69.6%) and 2,522 teeth (30.2%) and 424 fractured teeth (5.1%) on 103 skulls (49.8%). Both lesions affected significantly more adults than young adults. Overt periapical disease was associated with six teeth (0.1%) distributed across five skulls (2.4%). A carious lesion was present on one tooth (0.01%) of one specimen (0.5%). Lesions consistent with temporomandibular joint (TMJ) osteoarthritis were found in 24 specimens (11.6%), affecting 38 joints (9.2%). Trauma to the skull, such as bite marks, bullet holes or blunt trauma, was noted in 44 skulls (21.2%). The grey wolf and the domestic dog (Canis lupus familiaris) share common dental diseases; however, the proportion and severity may vary. Although the clinical significance of dental and TMJ pathology in the grey wolf remains unknown, based on the impact of these disorders on the domestic dog, the occurrence and severity of these lesions are likely to play an important role in the morbidity and mortality of this wild canid species.

Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues.

Vascular endothelial growth factor (VEGF) is a secreted heparin-binding mitogen; its growth-promoting activity is limited to vascular endothelial cells in vitro and VEGF also stimulates angiogenesis in vivo. To identify target cells for VEGF and investigate the potential physiological role of this factor, iodinated recombinant human VEGF (125I-rhVEGF) was used for in vitro ligand autoradiography on tissue sections from adult rats. 125I-rhVEGF exhibited saturable, displaceable binding to a single class of sites with high affinity and low capacity in all tissues and organs examined. Colocalization of 125I-rhVEGF binding with Factor VIII-like immunoreactivity demonstrated binding sites associated with vascular endothelial cells of both fenestrated and nonfenestrated microvessels and the endothelium of large vessels, while no displaceable binding was evident on nonendothelial cells. Specific binding was associated with quiescent as well as proliferating vessels. These findings support the hypothesis that VEGF plays a specific role in both the maintenance and in the induction of growth of vascular endothelial cells.

Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to Chinese hamster ovary cells.

Vascular endothelial growth factor (VEGF) is a mitogen with a specificity for endothelial cells in vitro and an angiogenic inducer in vivo. We tested the hypothesis that VEGF may confer on expressing cells a growth advantage in vivo. Dihydrofolatereductase--Chinese hamster ovary cells were transfected with expression vectors which direct the constitutive synthesis of VEGF. Neither the expression nor the exogenous administration of VEGF stimulated anchorage-dependent or anchorage-independent growth of Chinese hamster ovary cells in vitro. However, VEGF-expressing clones, unlike control cells, demonstrated an ability to proliferate in nude mice. Histologic examination revealed that the proliferative lesions were compact, well vascularized, and nonedematous. Ultrastructural analysis revealed that capillaries within the lesions were of the continuous type. These findings indicate that the expression of VEGF may confer on cells the ability to grow in vivo in the absence of transformation by purely paracrine mechanisms. Since VEGF is a widely distributed protein, this property may have relevance for a variety of physiological and pathological proliferative processes.

Dental Pathology of the Hoary Marmot (Marmota caligata), Groundhog (Marmota monax) and Alaska Marmot (Marmota broweri).

Museum specimens (maxillae and mandibles) of the three marmot species occurring in Alaska (Marmota caligata [n = 108 specimens], Marmota monax [n = 30] and Marmota broweri [n = 24]) were examined macroscopically according to predefined criteria. There were 71 specimens (43.8%) from female animals, 69 (42.6%) from male animals and 22 (13.6%) from animals of unknown sex. The ages of animals ranged from neonatal to adult, with 121 young adults (74.4%) and 41 adults (25.3%) included, and 168 excluded from study due to neonatal/juvenile age or incompleteness of specimens (missing part of the dentition). None of the teeth were missing, so 3,564 teeth were available for examination. All teeth were normal in morphology and none was affected by enamel hypoplasia. Two specimens displayed two supernumerary teeth each. One-third of specimens displayed attrition/abrasion and in 38.9% of these the change involved all premolar and molar teeth. The proportion of adult specimens affected by attrition/abrasion was three times as high as young adult specimens. Dental fractures were rare, noted in only two specimens, affecting 0.08% of teeth (n = 3). Periapical disease was also rare, with a striking lesion in one young adult female specimen. Some degree of periodontitis was seen in 26 specimens (16.1%), affecting 4.6% of premolar and molar teeth. The proportion of adults with periodontitis was over three times as high as that for young adults. Five specimens displayed mild malocclusion. Although the clinical significance of dental pathology in the marmot species of Alaska remains elusive, the occurrence and severity of some dental lesions may play an important role in their morbidity and mortality.

Dental and Temporomandibular Joint Pathology of the North American Brown Bear (Ursus arctos horribilis, Ursus arctos middendorffi and Ursus arctos sitkensis).

Museum specimens (maxillae and mandibles) from 393 North American brown bears (Ursus arctos) from Alaska were examined macroscopically according to predefined criteria and 204 specimens were included in this study. The specimens were acquired between 1905 and 2012. There were 99 specimens (48.5%) from male animals, 87 (42.7%) from female animals and 18 (8.8%) from animals of unknown sex. The ages of the animals ranged from neonate to adult, with 92 adults (45.1%) and 112 young adults (54.9%) included and neonates/juveniles excluded from the study. The number of teeth available for examination was 6,525 (76.2%); 8.6% of teeth were absent artefactually, 0.8% were deemed absent due to acquired tooth loss and 14.5% were absent congenitally. None of the brown bears had supernumerary teeth, persistent deciduous teeth or abnormally formed crowns. Only four of the specimens in the present population were affected by enamel hypoplasia and one specimen contained two mandibular fourth premolar teeth with one root instead of two. All 204 specimens displayed at least some degree of attrition/abrasion, affecting 63% of all teeth, ranging from mild wear of the enamel to deep abrasion associated with pulp exposure. Ten-times more adult than young adult specimens had abrasion causing pulp exposure, while more young adults showed mild attrition/abrasion. Dental fractures were noted in one-third of brown bears and in 3.0% of the total number of present teeth. More adult brown bears had dental fractures than young adults. There were 11 specimens (5.4%) that displayed overt periapical disease, affecting a total of 20 dental alveoli (0.22%), with adults significantly more affected than young adults. Some degree of periodontitis was seen in 145 specimens (71.1%), affecting 13.6% of all dental alveoli. Nearly one-third (29.9%) of skulls displayed skeletal and/or dental malocclusion, most commonly a level bite. Lesions consistent with temporomandibular joint (TMJ) osteoarthritis were found in 27 specimens (13.2%). Caries lesions were discovered in four specimens (2.0%), affecting eight teeth in total. Although the clinical significance of dental and TMJ pathology in the brown bear remains elusive, the occurrence and severity of some of these lesions may play an important role in the morbidity of this species.

Dental and Temporomandibular Joint Pathology of the American Black Bear (Ursus americanus).

Museum specimens (maxillae and/or mandibles) from 371 American black bears (Ursus americanus) acquired between 1889 and 2006 were examined macroscopically according to predefined criteria, and 348 were included in this study. Of the 348 specimens, 126 (36.2%) were from male animals, 106 (30.5%) were from female animals and 116 (33.3%) were from animals of unknown sex. Specimen ages ranged from young adult (n = 63, 18.1%) to adult (n = 285, 81.9%), with juveniles excluded from the study. The number of teeth available for examination was 12,019 (82.2%); 7.0% of teeth were absent artefactually, 0.4% were deemed absent due to acquired tooth loss and 9.7% were absent congenitally. In 43 specimens (12.3%), 82 teeth (0.68%) were small vestigial structures with crowns that were flush with the level of surrounding alveolar bone. The remaining teeth (99.3%) were of normal morphology. Only three supernumerary teeth and three instances of enamel hypoplasia were encountered. Persistent deciduous teeth or teeth with an aberrant number of roots were not encountered in any of the specimens. Approximately one-third of the teeth examined (4,543, 37.8%) displayed attrition/abrasion, affecting nearly all of the specimens (n = 338, 97.1%). Incisor and molar teeth accounted for 52.5% and 34.3% of the affected teeth, respectively, with significantly more adults affected than young adults. Dental fractures were noted in 63 bears, affecting 18.1% of specimens and 1.0% of the total number of present teeth. The canine teeth were most often fractured, with adults having significantly more complicated crown fractures of these teeth than young adults. There were 11 specimens (3.2%) that displayed periapical lesions, affecting 12 (0.1%) dental alveoli. There were 179 specimens (51.4%) displaying bony changes indicative of periodontitis, affecting 816 (6.8%) dental alveoli. The proportion of adult bears affected by periodontitis (57.9%) was significantly greater than that of young adults (22.2%). Exactly half of the specimens (n = 174) possessed lesions consistent with mild temporomandibular joint osteoarthritis. The occurrence and severity of the dental pathology encountered in this study may play an important role in the morbidity and mortality of the American black bear.

Beyond Men, Women, or Both: A Comprehensive, LGBTQ-Inclusive, Implicit-Bias-Aware, Standardized-Patient-Based Sexual History Taking Curriculum.

Introduction: This standardized-patient-based module prepares medical students to take inclusive, comprehensive sexual histories from patients of all sexual orientations and gender identities. Health disparities faced by lesbian, gay, bisexual, transgender, and queer (LGBTQ) people are at least partially the result of inadequate access to health care and insufficient provider training. This module incorporates implicit bias activities to emphasize the important role providers can play in mitigating these disparities through compassionate, competent care. Furthermore, two of the three included cases highlight the negative impact sexual dysfunction can have on emotional well-being. Methods: Over 3 hours, students participate in a 30-minute large-group lecture and three 40-minute small-group standardized patient encounters with debrief. Prework consists of a short video on sexual history taking, assigned readings, and an implicit bias activity. These materials are included in this resource, along with lecture slides, facilitator guide, and standardized patient cases. Though the cases are adaptable to all levels of medical education, this module is designed for second-year and early third-year medical students. Results: Qualitative student evaluations were positive, and postparticipation surveys revealed statistically significant improvement in comfort with their ability to take a sexual history in general, and take one from patients with a differing sexual orientation. Deployed in the second year of our Doctoring curriculum, this module continues to receive positive evaluations. Discussion: Introducing these skills begins to address the curricular deficiencies seen across medical education and lays the foundation for a more competent health care workforce to address the needs of LGBTQ patients.

Dental and Temporomandibular Joint Pathology of the Polar Bear (Ursus maritimus).

Museum specimens (maxillae and/or mandibles) from 317 polar bears (Ursus maritimus) were examined macroscopically according to predefined criteria and 249 specimens were included in this study. The specimens were acquired between 1906 and 2011. There were 126 specimens (50.6%) from male animals, 93 (37.3%) from female animals and 30 (12.1%) from animals of unknown sex. The ages of the animals ranged from neonate to adult, with 125 adults (50.2%) and 124 young adults (49.8%) included and neonates/juveniles excluded from the study. The number of teeth available for examination was 7,638 (73.5%); 12.3% of teeth were absent artefactually, 0.8% were deemed absent due to acquired tooth loss and 13.4% were absent congenitally. With respect to tooth morphology, 20 teeth (0.26% of available teeth) in 18 specimens (7.2% of available specimens) were small vestigial structures with crowns that were flush with the level of surrounding alveolar bone. One supernumerary tooth and one tooth with enamel hypoplasia were encountered. Persistent deciduous teeth and teeth with an aberrant number of roots were not found. Relatively few teeth (3.7%) displayed attrition/abrasion, 90% of which were the maxillary and mandibular incisor teeth, in 41 polar bears (16.5%). Nearly twice as many adult specimens exhibited attrition/abrasion as those from young adults; significantly more males were affected than females. Dental fractures were noted in 52 polar bears, affecting 20.9% of specimens and 1.3% of the total number of teeth present. More adult polar bears had dental fractures than young adults. There were 21 specimens (8.4%) that displayed overt periapical disease, affecting a total of 24 dental alveoli (0.23%). Some degree of periodontitis was seen in 199 specimens (79.9%); however, only 12.6% of dental alveoli had bony changes indicative of periodontitis. Lesions consistent with temporomandibular joint osteoarthritis (TMJ-OA) were found in 23 specimens (9.2%). TMJ-OA was significantly more common in adults than in young adults and in males than in females. Although the clinical significance of dental and TMJ pathology in the polar bear remains elusive, the occurrence and severity of these lesions may play an important role in the morbidity and mortality of this species.

Dental and Temporomandibular Joint Pathology of the Walrus (Odobenus rosmarus).

Maxillae and/or mandibles from 76 walruses (Odobenus rosmarus) were examined macroscopically according to predefined criteria. The museum specimens were acquired between 1932 and 2014. Forty-five specimens (59.2%) were from male animals, 29 (38.2%) from female animals and two (2.6%) from animals of unknown sex, with 58 adults (76.3%) and 18 young adults (23.7%) included in this study. The number of teeth available for examination was 830 (33.6%); 18.5% of teeth were absent artefactually, 3.3% were deemed to be absent due to acquired tooth loss and 44.5% were absent congenitally. The theoretical complete dental formula was confirmed to be I 3/3, C 1/1, P 4/3, M 2/2, while the most probable dental formula is I 1/0, C 1/1, P 3/3, M 0/0; none of the specimens in this study possessed a full complement of theoretically possible teeth. The majority of teeth were normal in morphology; only five teeth (0.6% of available teeth) were malformed. Only one tooth had an aberrant number of roots and only one supernumerary tooth was encountered. No persistent deciduous teeth were found in any of the young adult or adult specimens, nor were any specimens affected by enamel hypoplasia. The majority of teeth (85.5%) displayed attrition/abrasion. Of the adult and young adult specimens, 90.8% showed some degree of attrition/abrasion on at least one tooth. Tooth fractures were noted in eight walruses, affecting 10.5% of specimens and 1.3% of the total number of teeth, nearly three-quarters of which were maxillary canine teeth (tusks). Three specimens (3.9%), all adult males, displayed overt periapical disease. The majority (99.2%) of dental alveoli did not have bony changes indicative of periodontitis, with only five specimens (6.6%) affected by periodontitis. Lesions consistent with temporomandibular joint osteoarthritis (TMJ-OA) were found in 46 specimens (60.5%) and TMJ-OA was significantly more common in adults than young adults and males than females. Although the clinical significance of dental and TMJ pathology in the walrus remains unknown, the occurrence and severity of these lesions may play an important role in the morbidity and mortality of this species.

Regulation of learning by EphA receptors: a protein targeting study.

EphA family receptor tyrosine kinases and their ephrin-A ligands are involved in patterning axonal connections during brain development, but until now a role for these molecules in the mature brain had not been elucidated. Here, we show that both the EphA5 receptor and its ephrin-A ligands (2 and 5) are expressed in the adult mouse hippocampus, and the EphA5 protein is present in a phosphorylated form. Because there are no pharmacological agents available for EphA receptors, we designed recombinant immunoadhesins that specifically bind to the receptor binding site of the ephrin-A ligand (antagonist) or the ligand binding site of the EphA receptor (agonist) and thus target EphA function. We demonstrate that intrahippocampal infusion of an EphA antagonist immunoadhesin leads to impaired performance in two behavioral paradigms, T-maze spontaneous alternation and context-dependent fear conditioning, sensitive to hippocampal function, whereas activation of EphA by infusion of an agonist immunoadhesin results in enhanced performance on these tasks. Because the two behavioral tasks have different motivational, perceptual, and motor requirements, we infer the changes were not caused by these performance factors but rather to cognitive alterations. We also find bidirectional changes in gene expression and in electrophysiological measures of synaptic efficacy that correlate with the behavioral results. Thus, EphA receptors and their ligands are implicated as mediators of plasticity in the adult mammalian brain.