Extent Of Pathology Research Articles

Insecure Attachment Styles and Increased Borderline Personality Organization in Substance Use Disorders

Background: Previous research has linked insecure attachment styles and borderline personality organization to substance use disorder (SUD). However, it still remains unclear whether those impairments apply to different kinds of SUDs to the same extent. Therefore, in this study we sought to investigate potential differences regarding attachment deficits and borderline personality organization in two different SUD inpatient groups and furthermore in comparison to healthy controls. Sampling and Methods: A total of 66 (24 female) inpatients diagnosed with alcohol use disorder (AUD), 57 (10 female) inpatients diagnosed with polydrug use disorder (PUD), and 114 (51 female) healthy controls completed the Borderline Personality Inventory and the Attachment Style Questionnaire. Results: Compared to healthy controls, AUD and PUD inpatients showed significant deficits in all attachment parameters (p < 0.01) as well as a significantly increased amount of borderline personality organization (p < 0.01). No differences between AUD and PUD inpatients were observed (p > 0.05). Conclusions: Our results indicate that the drug(s) of choice cannot be regarded as an indicator for the extent of attachment deficits or personality pathology. These initial findings are mainly limited by the rather small sample size as well as just a single point of measurement. Future research might also consider further covariates such as comorbidity or psychotropic medication.

Pathophysiology of uveitis

SummaryThis talk will overview the pathophysiology of non‐infectious uveitis in relation to recent SUN (standardised uveitis nomenclature) disease classification. The experimental and translational human evidence of autoimmunity and activation of immunity will be discussed. In addition the talk will highlight the pathways and mechanisms of tissue damage that results in sight‐threatening disease. Traditionally, despite active immune regulatory mechanisms operative within the ocular environment, inflammation still occurs. Activated antigen and non‐antigen specific T cells are generated in uveitis. The interplay with innate immunity and in particular cells of myeloid lineage both systemically and within the local environment dictate the severity and extent of pathology we observe. The understanding of immune responses during the uveitis open many avenues to potential novel immunotherapies that not only suppress inflammation but attempt to redress immune balance, tolerance and local homeostasis within ocular tissues.

B4GALNT2 (GALGT2) Gene Therapy Reduces Skeletal Muscle Pathology in the FKRP P448L Mouse Model of Limb Girdle Muscular Dystrophy 2I

Overexpression of B4GALNT2 (previously GALGT2) inhibits the development of muscle pathology in mouse models of Duchenne muscular dystrophy, congenital muscular dystrophy 1A, and limb girdle muscular dystrophy 2D. In these models, muscle GALGT2 overexpression induces the glycosylation of α dystroglycan with the cytotoxic T cell glycan and increases the overexpression of dystrophin and laminin α2 surrogates known to inhibit disease. Here, we show that GALGT2 gene therapy significantly reduces muscle pathology in FKRP P448Lneo(-) mice, a model for limb girdle muscular dystrophy 2I. rAAVrh74.MCK.GALGT2-treated FKRP P448Lneo(-) muscles showed reduced levels of centrally nucleated myofibers, reduced variance, increased size of myofiber diameters, reduced myofiber immunoglobulin G uptake, and reduced muscle wasting at 3 and 6 months after treatment. GALGT2 overexpression in FKRP P448Lneo(-) muscles did not cause substantial glycosylation of α dystroglycan with the cytotoxic T cell glycan or increased expression of dystrophin and laminin α2 surrogates in mature skeletal myofibers, but it increased the number of embryonic myosin-positive regenerating myofibers. These data demonstrate that GALGT2 overexpression can reduce the extent of muscle pathology in FKRP mutant muscles, but that it may do so via a mechanism that differs from its ability to induce surrogate gene expression.

Distribution and Load of Amyloid-β Pathology in Parkinson Disease and Dementia with Lewy Bodies.

Parkinson disease (PD), Parkinson disease with dementia (PDD), and Dementia with Lewy bodies (DLB) differ clinically with regard to the presence and timing of dementia. In this postmortem study, we evaluated whether the burden and distribution pattern of amyloid-β (Aβ) pathology differs among these disease entities. We assessed Aβ phases and neuritic plaque scores in 133 patients fulfilling clinical diagnostic criteria for PD, PDD, and DLB, and determined the presence and load of Aβ pathology in 5 cortical and 4 subcortical regions in a subset of patients (n = 89) using a multispectral imaging system. Aβ phases and neuritic plaque scores were higher in DLB versus PDD (both p < 0.001) and in PDD vs PD patients (p = 0.020 and 0.022, respectively). Aβ pathology was more often observed in the entorhinal cortex, amygdala and putamen in DLB versus PDD patients; Aβ load was higher in both cortical and subcortical regions. PDD patients had more frequent Aβ pathology in temporal cortex and higher Aβ load in cortical regions and striatum versus PD patients. Our findings suggest that the load and extent of Aβ pathology may contribute to cognitive dysfunction in PDD and the early-stage severe dementia in DLB.

Clinical and pathological outcomes after resection of intramedullary spinal cord tumors: a single-institution case series.

OBJECTIVE The objective of this study was to identify clinically relevant predictors of progression-free survival and functional outcomes in patients who underwent surgery for intramedullary spinal cord tumors (ISCTs). METHODS An institutional spinal tumor registry and billing records were reviewed to identify adult patients who underwent resection of ISCTs between 1993 and 2014. Extensive data were collected from patient charts and operative notes, including demographic information, extent of resection, tumor pathology, and functional and oncological outcomes. Survival analysis was used to determine important predictors of progression-free survival. Logistic regression analysis was used to evaluate the association between an "optimal" functional outcome on the Frankel or McCormick scale at 1-year follow-up and various clinical and surgical characteristics. RESULTS The consecutive case series consisted of 63 patients (50.79% female) who underwent resection of ISCTs. The mean age of patients was 41.92 ± 14.36 years (range 17.60-75.40 years). Complete microsurgical resection, defined as no evidence of tumor on initial postoperative imaging, was achieved in 34 cases (54.84%) of the 62 patients for whom this information was available. On univariate analysis, the most significant predictor of progression-free survival was tumor histology (p = 0.0027). Patients with Grade I/II astrocytomas were more likely to have tumor progression than patients with WHO Grade II ependymomas (HR 8.03, 95% CI 2.07-31.11, p = 0.0026) and myxopapillary ependymomas (HR 8.01, 95% CI 1.44-44.34, p = 0.017). Furthermore, patients who underwent radical or subtotal resection were more likely to have tumor progression than those who underwent complete resection (HR 3.46, 95% CI 1.23-9.73, p = 0.018). Multivariate analysis revealed that tumor pathology was the only significant predictor of tumor progression. On univariate analysis, the most significant predictors of an "optimal" outcome on the Frankel scale were age (OR 0.94, 95% CI 0.89-0.98, p = 0.0062), preoperative Frankel grade (OR 4.84, 95% CI 1.33-17.63, p = 0.017), McCormick score (OR 0.22, 95% CI 0.084-0.57, p = 0.0018), and region of spinal cord (cervical vs conus: OR 0.067, 95% CI 0.012-0.38, p = 0.0023; and thoracic vs conus: OR 0.015: 95% CI 0.001-0.20, p = 0.0013). Age, tumor pathology, and region were also important predictors of 1-year McCormick scores. CONCLUSIONS Extent of tumor resection and histopathology are significant predictors of progression-free survival following resection of ISCTs. Important predictors of functional outcomes include tumor histology, region of spinal cord in which the tumor is present, age, and preoperative functional status.

SOCS-3 Regulates Alveolar Bone Loss in Experimental Periodontitis

The host immune response plays a key role in bacteria-induced alveolar bone resorption. Endogenous control of the magnitude and duration of inflammatory signaling is considered an important determinant of the extent of periodontal pathology. Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathways and may play a role in restraining periodontal inflammation. We hypothesized that SOCS-3 regulates alveolar bone loss in experimental periodontitis. Periodontal bone loss was induced in 16-wk-old myeloid-specific SOCS-3-knockout and wild-type (WT) C57Bl6-B.129 mice by oral inoculation 9 times with 109 colony-forming units of Porphyromonas gingivalis A7436 through an oral gavage model for periodontitis. Sham controls for both types of mice received vehicle without bacteria. The mice were euthanized 6 wk after the last oral inoculation. Increased bone loss was demonstrated in P. gingivalis–infected SOCS-3-knockout mice as compared with P. gingivalis–infected WT mice by direct morphologic measurements, micro–computed tomography analyses, and quantitative histology. Loss of SOCS-3 function resulted in an increased number of alveolar bone osteoclasts and increased RANKL expression after P. gingivalis infection. SOCS-3 deficiency in myeloid cells also promotes a higher P. gingivalis lipopolysaccharide-induced inflammatory response with higher secretion of IL-1β, IL-6, and KC (IL-8) by peritoneal macrophages as compared with WT controls. Our data implicate SOCS-3 as a critical negative regulator of alveolar bone loss in periodontitis.

Preoperative diagnostic imaging and planning

A correctly chosen radiographic technique, good image quality and correct image interpretation are the basis of all surgical planning. It is only when the cause and extent of the hip pathology are evaluated carefully based on radiologic imaging that the long-term surgical success of hip and pelvis osteotomy is possible. This article gives an overview over performance, quality criteria and interpretation of the most important radiographic images of the hip. The anterior-posterior pelvic view is the most important radiograph for planning an osteotomy of the hip. Besides the evaluation of the underlying cause, the caput-collum-diaphyseal angle (CCD) can be calculated from the pelvic view. For the evaluation of the real femoral antetorsion angle (AT-angle) a RippsteinII projection needs to be performed. Lequesne's false-profile view is important to assess the ventral part of the joint, especially to measure the anterior coverage of the femoral head. In neonates and children, the pelvic hip view is important to assess hip dysplasia. The relevant characteristic lines and angles that should evaluated in the pelvic hip view are the Hilgenreiner line, of the Perkin line, the acetabular angle (AC-angle) and Reimers migration index. Computed tomography allows 3D surgical planning and is the most accurate technique for measuring the AT-angle. Magnet resonance imaging is of help for the evaluation of hip pathologies such as labrum and cartilage injuries. MRI for this purpose should always be performed as anMR-arthrography.

Ultra-high field MTR and qR2* differentiates subpial cortical lesions from normal-appearing gray matter in multiple sclerosis

Background: Cortical gray matter (GM) demyelination is frequent and clinically relevant in multiple sclerosis (MS). Quantitative magnetic resonance imaging (qMRI) sequences such as magnetization transfer ratio (MTR) and quantitative R2* (qR2*) can capture pathological subtleties missed by conventional magnetic resonance imaging (MRI) sequences. Although differences in MTR and qR2* have been reported between lesional and non-lesional tissue, differences between lesion types or lesion types and myelin density matched normal-appearing gray matter (NAGM) have not been found or investigated. Objective: Identify quantitative differences in histopathologically verified GM lesion types and matched NAGM at ultra-high field strength. Methods: Using 7T post-mortem MRI, MRI lesions were marked on T2 images and co-registered to the calculated MTR and qR2* maps for further evaluation. In all, 15 brain slices were collected, containing a total of 74 cortical GM lesions and 45 areas of NAGM. Results: Intracortical lesions had lower MTR and qR2* values compared to NAGM. Type I lesions showed lower MTR than type III lesions. Type III lesions showed lower MTR than matched NAGM, and type I and IV lesions showed lower qR2* than matched NAGM. Conclusion: qMRI at 7T can provide additional information on extent of cortical pathology, especially concerning subpial lesions. This may be relevant for monitoring disease progression and potential treatment effects.

EVALUATION OF TAU BURDEN IN A CROSS-SECTIONAL COHORT OF ALZHEIMER’S DISEASE SUBJECTS USING [18F]GTP1 (GENENTECH TAU PROBE 1)

In Alzheimer’s disease (AD), the extent and density of tau pathology (intracellular aggregates of hyperphosphorylated tau) correlates with disease severity prior to death. [18F]GTP1 is a tau PET tracer that exhibits rapid pharmacokinetics, enabling the use of SUVR60-90min as a surrogate measure of tau specific binding, and robust test-retest reliability. Here, we report the preliminary results on the distribution of tau pathology, assessed by [18F]GTP1 PET imaging, and its relationship with symptomatic severity in an AD cross-sectional cohort enrolling as part of a longitudinal 18-month natural history study. Subjects were enrolled in an ongoing longitudinal natural history study; enrollment goals: 5 amyloid(-) and 5 amyloid (+) cognitively normal (MMSE 28-30, CDR 0), 20 prodromal AD (amyloid(+), MMSE 24-30, CDR = 0.5), 20 mild AD (amyloid(+), MMSE 22-30, CDR 0.5 or 1) and 10 moderate AD (amyloid(+), MMSE 16-21, CDR 1 or 2), all subjects are between the age of 50 and 80, inclusive. Clinical evaluations include MMSE, ADAS-cog-13, CDR, RBANS, and Stroop color naming. [18F]GTP1 images are being acquired over a 30-minute window starting 60 minutes post injection. The cerebellum gray has been shown to be an adequate reference region to estimate the non-displaceable component in cortical regions1, thus is being used to calculate SUVR. Consistent with observations from a first-in-human study, visual inspection of images suggest [18F]GTP1 exhibits a wide dynamic range and allows differentiation between AD and healthy controls, and between regions of predicted high and low tau pathology burden ((1)). In addition, we are investigating how global [18F]GTP uptake relates with global measures of clinical severity, and how regional distribution of [18F]GTP uptake relates to specific cognitive deficits. Interim analysis from this ongoing study will be presented. [18F]GTP1 is currently under evaluation in a longitudinal natural history study. Preliminary cross-sectional results reveal how the extent of GTP1 uptake relates to clinical cognitive and functional deficits in AD.

18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers.

Tau positron emission tomography ligands provide the novel possibility to image tau pathology in vivo However, little is known about how in vivo brain uptake of tau positron emission tomography ligands relates to tau aggregates observed post-mortem. We performed tau positron emission tomography imaging with (18)F-AV-1451 in three patients harbouring a p.R406W mutation in the MAPT gene, encoding tau. This mutation results in 3- and 4-repeat tau aggregates similar to those in Alzheimer's disease, and many of the mutation carriers initially suffer from memory impairment and temporal lobe atrophy. Two patients with short disease duration and isolated memory impairment exhibited (18)F-AV-1451 uptake mainly in the hippocampus and adjacent temporal lobe regions, correlating with glucose hypometabolism in corresponding regions. One patient died after 26 years of disease duration with dementia and behavioural deficits. Pre-mortem, there was (18)F-AV-1451 uptake in the temporal and frontal lobes, as well as in the basal ganglia, which strongly correlated with the regional extent and amount of tau pathology in post-mortem brain sections. Amyloid-β ((18)F-flutemetamol) positron emission tomography scans were negative in all cases, as were stainings of brain sections for amyloid. This provides strong evidence that (18)F-AV-1451 positron emission tomography can be used to accurately quantify in vivo the regional distribution of hyperphosphorylated tau protein.

Differences in Whole Blood Gene Expression Associated with Infection Time-Course and Extent of Fetal Mortality in a Reproductive Model of Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Infection.

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection of pregnant females causes fetal death and increased piglet mortality, but there is substantial variation in the extent of reproductive pathology between individual dams. This study used RNA-sequencing to characterize the whole blood transcriptional response to type 2 PRRSV in pregnant gilts during the first week of infection (at 0, 2, and 6 days post-inoculation), and attempted to identify gene expression signatures associated with a low or high level of fetal mortality rates (LFM and HFM; n = 8/group) at necropsy, 21 days post-inoculation. The initial response to infection measured at 2 days post-inoculation saw an upregulation of genes involved in innate immunity, such as interferon-stimulated antiviral genes and inflammatory markers, and apoptosis. A concomitant decrease in expression of protein synthesis and T lymphocyte markers was observed. By day 6 the pattern had reversed, with a drop in innate immune signaling and an increase in the expression of genes involved in cell division and T cell signaling. Differentially expressed genes (DEGs) associated with extremes of litter mortality rate were identified at all three time-points. Among the 15 DEGs upregulated in LFM gilts on all three days were several genes involved in platelet function, including integrins ITGA2B and ITGB3, and the chemokine PF4 (CXCL4). LFM gilts exhibited a higher baseline expression of interferon-stimulated and pro-inflammatory genes prior to infection, and of T cell markers two days post-infection, indicative of a more rapid progression of the immune response to PRRSV. This study has increased our knowledge of the early response to PRRSV in the blood of pregnant gilts, and could ultimately lead to the development of a biomarker panel that can be used to predict PRRSV-associated reproductive pathology.

Nonrandomized comparison of neurofibromatosis type 1 and non-neurofibromatosis type 1 children who received carboplatin and vincristine for progressive low-grade glioma: A report from the Children's Oncology Group.

To evaluate tumor responses, event-free survival (EFS), overall survival (OS), and toxicity of chemotherapy, children with neurofibromatosis type 1 (NF1) and progressive low-grade glioma were enrolled into the Children's Oncology Group (COG) A9952 protocol and treated with carboplatin and vincristine (CV). Non-NF1 patients were randomized to CV or thioguanine, procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, and vincristine in COG A9952. NF1 patients were assigned to CV only. NF1 patients and non-NF1 patients who were treated with CV were compared with respect to baseline characteristics, toxicity, tumor responses, EFS, and OS. A total of 127 eligible patients with NF1 were nonrandomly assigned to CV: 42 NF1 patients (33%) had events, and 6 (4.7%) died. The 5-year EFS rate was 69% ± 4% for the CV-NF1 group and 39% ± 4% for the CV-non-NF1 group (P < .001). In a univariate analysis, NF1 children had a significantly higher tumor response rate and superior EFS and OS in comparison with CV-treated children without NF1. NF1 patients and non-NF1 patients differed significantly in amount of residual tumor, extent of resection, tumor location, and pathology. According to a multivariate analysis, NF1 was independently associated with better EFS (P < .001) but not with OS. NF1 patients also had a decreased risk of grade 3 or 4 toxicities in comparison with non-NF1 patients. Three second malignant neoplasms occurred in NF1 patients receiving CV (CV-NF1 group) at a median of 7.8 years (range, 7.3-9.4 years) after enrollment, but there were none in the non-NF1 group. Children with NF1 tolerated CV well and had tumor response rates and EFS that were superior to those for children without NF1. Cancer 2016;122:1928-36. © 2016 American Cancer Society.

Somatosensory and auditory startle reaction in patients with movement disorders

Background Startle reflex (SR) is a generalized defense reaction which is elicited by unexpected stimuli. To elicit SR, auditory and electrical stimulations are used in electrophysiological investigations. Somatosensory startle reflex (SS-SR) is recently described in healthy volunteers after median and tibial stimulation. Studies in patients with brainstem lesions showed importance of upper brainstem in development of SS-SR. Here, we aim to investigate SS-SR systematically in various movement disorders to address its characteristics in comparison to ASR. Methods We have examined ASR and SS-SR in patients with dystonia ( n = 12), multiple system atrophy ( n = 8), corticobasal degeneration ( n = 5), restless legs syndrome ( n = 14), progressive supranuclear palsy ( n = 11), essential tremor ( n = 18) and idiopathic PD (n = 16) and healthy volunteers ( n = 35) under the same conditions. ASR and SS-SR were recorded over orbicularis oculi (o.oc), sternocleidomastoid (SCM), and biceps brachii (BB) after bilateral auditory and median nerve electrical stimulations, respectively. Results The pattern and probability rates over each three muscle of ASR were similar in MSA, RLS, ET, PD and healthy individuals. Probability rates of responses over each muscle and total ASR probability were the highest in dystonia group whereas they were the lowest in CBD and PSP ( p o.oc = 0.016, p scm = 0.036, p bb = 0.000, p total = 0.009). Onset latencies of O.oc responses were also longer in CBD and PSP groups ( p = 0.001). Presence of SSR was also the highest in dystonia and lowest in PSP group similar to ASR. Latency of O.oc response was longest in CBD group. Pattern of SS-SR was similar to healthy individuals in all disease groups except dystonia and MSA in which BB responses were more common than SCM responses. Conclusions The findings of ASR parallel the previous findings. Dystonia patients are known to have exaggerated ASRs. The decreased response in PSP was previously suggested as a support to show extent of pathology. Findings regarding SS-SR also parallel ASR. SS-SR is also exaggerated in dystonia. Different pattern of response appears to be a reflection of overflow phenomenon. However, development of withdrawal reaction is a possibility. Shorter onset latencies in dystonia group probably also reflect increased excitability. Absence of SS-SR or longer latencies in PSP reflects impairment of its pathway which supports the opinion that it may share pathway with ASR and its generator is possibly in the upper brainstem.

Increased, but Functionally Impaired, CD14+ HLA-DR–/low Myeloid-Derived Suppressor Cells in Psoriasis: A Mechanism of Dysregulated T Cells

The clinical extent of psoriasis pathology is regulated in part by defects in immune networks, including a defect in the suppressive actions of regulatory T cells. Recently, CD14(+) HLA-DR(-/low) monocytic myeloid-derived suppressor cells (Mo-MDSCs) have been shown to suppress T-cell activation as one of their suppressive mechanisms. However, little is known about the role of Mo-MDSCs and their functional relationship to T-cell suppression in relation to human chronic immune-mediated inflammatory diseases, including psoriasis. Despite psoriasis being a hyperinflammatory condition, Mo-MDSCs were elevated in psoriatic patient peripheral blood mononuclear cells compared to nonpsoriatic healthy controls (2.6% vs. 0.9%, P < 0.002). Freshly isolated psoriatic Mo-MDSCs directly suppressed CD8 T-cell proliferation less efficiently than healthy control Mo-MDSCs. In addition, psoriatic Mo-MDSCs expressed reduced surface expression of programmed cell death protein 1 compared to healthy controls. Additional invitro assays also demonstrated that psoriatic and control Mo-MDSCs both induce regulatory T-cell conversion from naïve T effector cells, but, importantly, the regulatory T cells induced by psoriatic Mo-MDSCs displayed decreased suppressive functionality. These results suggest that aberrations in psoriatic Mo-MDSCs prevent proper suppression of effector T-cell expansion and hamper the immune system's ability to correctly self-regulate.

An assessment of animal welfare for the culling of peri-urban kangaroos

Context Shooting is used to reduce the abundance of kangaroo (Macropus sp.) populations in many peri-urban areas in Australia, but there is uncertainty surrounding the animal welfare outcomes of this practice. Aim We assessed the animal welfare outcomes of night shooting for peri-urban eastern grey kangaroos (Macropus giganteus). We quantified the duration of stress for: (1) shot animals; (2) euthanased pouch young; and (3) other animals in the same social group. Methods An independent observer collected thermal imagery data, enabling four key animal welfare parameters to be quantified: instantaneous death rate, median time to death, wounding rate and flight duration of conspecifics. The duration between pouch removal and insensibility was recorded for pouch young. Post-mortem data were recorded to confirm the location and extent of pathology from shooting. Key results Of the 136 kangaroos that were shot at, two were missed. The wounding rate was zero, with a 98% instantaneous death rate. The median time to death for the three animals not killed instantaneously was 12 s. For pouch young considered sentient, the median stress time was 4 s. Kaplan–Meier survival analysis revealed that the median flight duration of conspecifics was 5 s. Conclusions Our results indicate that night shooting produces a very short duration of stress to shot kangaroos, their pouch young and their conspecifics. Implications When compared to other wildlife shooting methods, night shooting is a humane method for culling peri-urban kangaroos.

Clinicopathological Features of Ophthalmic Neoplasms Arising in the Setting of Xeroderma Pigmentosum

Background: Patients with xeroderma pigmentosum (XP) are strongly predisposed to the development of numerous cutaneous cancers. However, the extent of ocular pathology in these patients has not been adequately studied. Methods: We conducted a retrospective study of tumors involving the ocular surface and ocular adnexa from 6 XP patients. Histopathological evaluation and immunohistochemistry was performed using antibodies directed against the most common mutated proteins in XP (XPA, XPC, and XPD). Results: Patients included 4 males and 2 females with a mean age of 20.8 years (range 10-31) who met the clinical criteria for XP and were found to have a total of 13 neoplasms involving the ocular surface and adnexal skin; 6 squamous cell carcinomas (SCC), 3 cases of conjunctival intraepithelial neoplasia, 2 malignant melanomas, 1 basal cell carcinoma, and 1 atypical fibroxanthoma. Complete XPD loss was present in two tumors from 1 patient, suggesting a germline defect, and in the invasive component of an SCC from a second patient, suggesting a somatic alteration. No clear pattern of loss for XPA or XPC was evident. Conclusions: Our study outlines our early experience with the pathology of ocular neoplasms in XP patients. These findings deserve further exploration with genetic studies and additional patients.

Making Sense of Sellar Region Pathology

Lesions in the sellar and parasellar regions are encountered frequently in clinical radiology. Complex anatomy of this region contains numerous key structures, which can be affected by a variety of pathologic processes. Although “SATCHMO,” a commonly used mnemonic, may help the radiologist to remember differential diagnoses when imaging findings overlap, it has limited diagnostic utility. (See page 7 for description of SATCHMO.) A systematic approach to imaging findings in the sellar region can provide valuable information regarding the extent of pathology, aid in treatment planning, and help detect complications. This article discusses regional anatomy, clinical presentation, pathophysiology, and imaging characteristics of common sellar region pathology.

Deletion of Galgt2 (B4Galnt2) Reduces Muscle Growth in Response to Acute Injury and Increases Muscle Inflammation and Pathology in Dystrophin-Deficient Mice

Transgenic overexpression of Galgt2 (official name B4Galnt2) in skeletal muscle stimulates the glycosylation of α dystroglycan (αDG) and the up-regulation of laminin α2 and dystrophin surrogates known to inhibit muscle pathology in mouse models of congenital muscular dystrophy 1A and Duchenne muscular dystrophy. Skeletal muscle Galgt2 gene expression is also normally increased in the mdx mouse model of Duchenne muscular dystrophy compared with the wild-type mice. To assess whether this increased endogenous Galgt2 expression could affect disease, we quantified muscular dystrophy measures in mdx mice deleted for Galgt2 (Galgt2(-/-)mdx). Galgt2(-/-) mdx mice had increased heart and skeletal muscle pathology and inflammation, and also worsened cardiac function, relative to age-matched mdx mice. Deletion of Galgt2 in wild-type mice also slowed skeletal muscle growth in response to acute muscle injury. In each instance where Galgt2 expression was elevated (developing muscle, regenerating muscle, and dystrophic muscle), Galgt2-dependent glycosylation of αDG was also increased. Overexpression of Galgt2 failed to inhibit skeletal muscle pathology in dystroglycan-deficient muscles, in contrast to previous studies in dystrophin-deficient mdx muscles. This study demonstrates that Galgt2 gene expression and glycosylation of αDG are dynamically regulated in muscle and that endogenous Galgt2 gene expression can ameliorate the extent of muscle pathology, inflammation, and dysfunction in mdxmice.

Pathophysiology of uveitis

SummaryThis talk will overview the pathophysiology of non‐infectious uveitis in relation to recent SUN (standardised uveitis nomenclature) disease classification. The experimental and translational human evidence of autoimmunity and activation of immunity will be discussed. In addition the talk will highlight the pathways and mechanisms of tissue damage that results in sight‐threatening disease. Traditionally, despite active immune regulatory mechanisms operative within the ocular environment, inflammation still occurs. Activated antigen and non‐antigen specific T cells are generated in uveitis. The interplay with innate immunity and in particular cells of myeloid lineage both systemically and within the local environment dictate the severity and extent of pathology we observe. The understanding of immune responses during the uveitis open many avenues to potential novel immunotherapies that not only suppress inflammation but attempt to redress immune balance, tolerance and local homeostasis within ocular tissues.

Multimodality Imaging Assessment of Prosthetic Heart Valves.

Echocardiography and fluoroscopy are the main techniques for prosthetic heart valve (PHV) evaluation, but because of specific limitations they may not identify the morphological substrate or the extent of PHV pathology. Cardiac computed tomography (CT) and magnetic resonance imaging (MRI) have emerged as new potential imaging modalities for valve prostheses. We present an overview of the possibilities and pitfalls of CT and MRI for PHV assessment based on a systematic literature review of all experimental and patient studies. For this, a comprehensive systematic search was performed in PubMed and Embase on March 24, 2015, containing CT/MRI and PHV synonyms. Our final selection yielded 82 articles on surgical valves. CT allowed adequate assessment of most modern PHVs and complemented echocardiography in detecting the obstruction cause (pannus or thrombus), bioprosthesis calcifications, and endocarditis extent (valve dehiscence and pseudoaneurysms). No clear advantage over echocardiography was found for the detection of vegetations or periprosthetic regurgitation. Whereas MRI metal artifacts may preclude direct prosthesis analysis, MRI provided information on PHV-related flow patterns and velocities. MRI demonstrated abnormal asymmetrical flow patterns in PHV obstruction and allowed prosthetic regurgitation assessment. Hence, CT shows great clinical relevance as a complementary imaging tool for the diagnostic work-up of patients with suspected PHV obstruction and endocarditis. MRI shows potential for functional PHV assessment although more studies are required to provide diagnostic reference values to allow discrimination of normal from pathological conditions.