Intervertebral disc degeneration in warmblood horses: Histological and biochemical characterization

Gross morphology of healthy and degenerated intervertebral discs (IVDs) is largely similar in horses as in dogs and humans. For further comparison, the biochemical composition and the histological and biochemical changes with age and degeneration were analyzed in 41 warmblood horses. From 33 horses, 139 discs and 2 fetal vertebral columns were evaluated and scored histologically. From 13 horses, 73 IVDs were assessed for hydration, DNA, glycosaminoglycans, total collagen, hydroxyl-lysyl-pyridinoline, hydroxylysine, and advanced glycation end-product (AGE) content. From 7 horses, 20 discs were assessed for aggrecan, fibronectin, and collagen type 1 and 2 content. Histologically, tearing of the nucleus pulposus (NP) and cervical annulus fibrosus (AF), and total histological score (tearing and vascular proliferation of the AF, and chondroid metaplasia, chondrocyte-like cell proliferation, presence of notochordal cells, matrix staining, and tearing of the NP) correlated with gross degeneration. Notochordal cells were not seen in IVDs of horses. Age and gross degeneration were positively correlated with AGEs and a fibrotic phenotype, explaining gross degenerative changes. In contrast to dogs and humans, there was no consistent difference in glycosaminoglycan content and hydration between AF and NP, nor decrease of these variables with age or degeneration. Hydroxylysine decrease and collagen 1 and AGEs increase were most prominent in the NP, suggesting degeneration started in the AP. In caudal cervical NPs, AGE deposition was significantly increased in grossly normal IVDs and total collagen significantly increased with age, suggesting increased biomechanical stress and likelihood for spinal disease in this part of the vertebral column.

A Review on Frozen Shoulder: Pathophysiology and Its Associated Diagnosis

Background: Frozen shoulder is a commonly occurring disease of the population. It is also referred to as shoulder capsulitis. It causes pain and stiffness of the shoulder and dominant in left shoulder. Various things are still unclear regarding the treatment and causes of this disease. It is a painful and n quickly healed disease. Patients show recovery but are often unable to regain their full potential movements. Painful stiffness of the shoulder is an ill-described medical entity, this is hard to evaluate and sensitive to treat. The nomenclature sed and consists of phrinclude cluding frozen shoulder, adhesive capsulitis, focal dystrophy, stiff shoulder, shriveled shoulder, and following. Apart from its idiopathic form, the disease can be initiated with the resource of the usage of trauma, infection, tumor, radiation, systemic and neighborhood metabolic concerns. Patho- anatomically, the common place region denominates an inflammatory vascular proliferation found with the resource of the usage thickening, scarring, and retraction of the joint cover. Summary: The inflammatory technique frequently begins to evolved on the rotator language and can increase to the subacromial space. Clinical analysis is primarily based totally records and bodily examination. Generally, the onset of ache precedes the belief of a discounted variety of movement with the aid of using weeks or months. In early ranges of ailment, the inflammatory form of ache dominates, the patient's most important criticism is ache at night. In the later stage, variety of movement step by step decreases. Patients no longer frequently whine approximately decreased movement, likely due to its gradual onset. Conclusion: Treatment options are a mixture of mobilization carrying sports with intra-articular steroids, hydraulic distension of the joint capsule, manipulation below anaesthesia,arthroscopic and/or open arthrosis.The appropriate preference of protocol is really as critical as its correct timing. In the inflammatory phase, competitive invasive protocols are uncommon, but deleterious and therefore need to be taken into consideration. New anti- angiogenic outlets also can moreover enhance beneficial effects and shorten the rehabilitation phase.

MiR-34a-3p suppresses pulmonary vascular proliferation in acute pulmonary embolism rat by targeting DUSP1

Background: Acute pulmonary embolism (APE) is a prevalent reason of cardiovascular morbidity and mortality. Recent studies have underscored the positive effects of miRNAs on many diseases. The present study aimed to identify the critical miRNA with differential expressions and explore its role in APE. Methods: The critical miRNA with its target gene was screened by bioinformatics analysis. Their binding relationship was analyzed by Targetscan, dual-luciferase reporter and RNA pull-down assays. A rat model of APE was established by self-blood coagulum. Human pulmonary artery smooth muscle cells (PASMCs) were exposed to platelet-derived growth factor (PDGF-BB) for excessive proliferation, and transfected with miR-34a-3p mimic. Mean pulmonary arterial pressure (mPAP) of rat was measured, and the pulmonary tissues were used for the pathological observation by Hematoxylin-eosin (H&E) staining. Cell viability and proliferation were detected by Cell Counting Kit-8 (CCK-8) and EdU assays. The expressions of miR-34a-3p with its target genes (including DUSP1), NOR-1 and PCNA were determined by quantitative reverse transcription polymerase chain reaction (RT-qPCR) or/and western blot. Results: MiR-34a-3p expression was downregulated in APE patients, which attenuated the increment of mPAP and thickening of the pulmonary arterial walls in APE rats, accompanied with regulation of NOR-1 and PCNA levels. MiR-34a-3p suppressed DUSP1 expression by directly binding to its 3’-UTR, and attenuated cell viability, proliferation, and the expressions of NOR-1 and PCNA in PDGF-BB-induced PASMCs by inhibiting DUSP1 expression. Conclusion: Upregulated miR-34a-3p negatively regulates DUSP1 expression to inhibit PASMC proliferation, which, thus, may act on APE treatment by negatively regulating pulmonary vascular proliferation.

Proteomic Distributions in CD34+ Microvascular Niche Patterns of Glioblastoma

The poor clinical prognosis and microvascular patterns of glioblastoma (GBM) are of serious concern to many clinicians and researchers. However, very few studies have examined the correlation between microvascular niche patterns (MVNPs) and proteomic distribution. In this study, CD34 immunofluorescence staining and matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-IMS) technology were used to investigate the protein distributions in MVNPs. CD34+ microvascular phenotype could be divided into four types: microvascular sprouting (MS), vascular cluster (VC), vascular garland (VG), and glomeruloid vascular proliferation (GVP). Based on such characteristics, MVNPs were divided into two types by cluster analysis, namely, type I, comprising primarily MS and VC, and type II, comprising many VGs and GVPs. Survival analysis indicated the type of MVNPs to be an independent prognostic factor for progression-free and overall survival in GBM. MALDI-IMS results showed the peaks at m/z 1037 and 8960 to exhibit stronger ion signals in type II, while those at m/z 3240 and 3265 exhibited stronger ion signals in type I. The findings may assist future research on therapy and help predict prognosis in GBM. However, due to the limited number of studies, more well-designed studies are warranted to further verify our results.

TAMI-22. SEGMENTATION OF DISTINCT TUMOR HALLMARKS OF GLIOBLASTOMA ON DIGITAL HISTOPATHOLOGY USING A HIERARCHICAL DEEP LEARNING APPROACH

PURPOSE Glioblastoma is a highly heterogeneous brain tumor. Primary treatment for glioblastoma involves maximally-safe surgical resection. After surgery, resected tissue slides are visually analyzed by neuro-pathologists to identify distinct histological hallmarks characterizing glioblastoma including high cellularity, necrosis, and vascular proliferation. In this work, we present a hierarchical deep learning-based strategy to automatically segment distinct Glioblastoma niches including necrosis, cellular tumor, and hyperplastic blood vessels, on digitized histopathology slides. METHODS We employed the IvyGap cohort for which Hematoxylin and eosin (H&E) slides (digitized at 20X magnification) from n=41 glioblastoma patients were available. Additionally, expert-driven segmentations of cellular tumor, necrosis, and hyperplastic blood vessels (along with other histological attributes) were made available. We randomly employed n=120 slides from 29 patients for training, n=38 slides from 6 cases for validation, and n=30 slides from 6 patients to feed our deep learning model based on Residual Network architecture (ResNet-50). ~2,000 patches of 224x224 pixels were sampled for every slide. Our hierarchical model included first segmenting necrosis from non-necrotic (i.e. cellular tumor) regions, and then from the regions segmented as non-necrotic, identifying hyperplastic blood-vessels from the rest of the cellular tumor. RESULTS Our model achieved a training accuracy of 94%, and a testing accuracy of 88% with an area under the curve (AUC) of 92% in distinguishing necrosis from non-necrotic (i.e. cellular tumor) regions. Similarly, we obtained a training accuracy of 78%, and a testing accuracy of 87% (with an AUC of 94%) in identifying hyperplastic blood vessels from the rest of the cellular tumor. CONCLUSION We developed a reliable hierarchical segmentation model for automatic segmentation of necrotic, cellular tumor, and hyperplastic blood vessels on digitized H&E-stained Glioblastoma tissue images. Future work will involve extension of our model for segmentation of pseudopalisading patterns and microvascular proliferation.

Mixed chorangioma and leiomyoma of the placenta, with a brief review of nontrophoblastic placental lesions

Chorangioma is the most common type of primary non-trophoblastic tumor of the placenta, usually identified incidentally on ultrasound or at delivery. Leiomyomas within the placenta have been described, though they are rare and usually of maternal origin. We present an unusual case of a placental tumor with combined histopathologic and immunohistochemical features of both chorangioma and leiomyoma. A 39-year-old woman was found to have an echogenic placental mass at 33 weeks of gestation on ultrasound, that was thought to be a chorangioma. They followed up weekly, and performed a cesarean section at 39 weeks, due to concern for intrauterine growth restriction. No fetal or maternal complications occurred. Grossly, a 9-cm, red-brown mass with a broad-based stalk was identified on the fetal surface of the placenta near the periphery. Microscopically, the lesion was found to display characteristic features of chorangioma, with vascular proliferation, which stained positive for CD34 and CD31. SMA and caldesmon immunohistochemical staining was also positive, highlighting the proliferation of smooth muscle throughout the neoplasm. Literature review revealed a single additional case with similar characteristics.

Cystic angiomatosis of the bone, liver, and spleen

Introduction/Objective Cystic angiomatosis is a very rare entity characterized by multifocal cystic angiomatous lesions of the skeletal system, occasionally involving visceral organ systems. Clinical presentation and progression are extremely variable. Cases with liver involvement are even rarer, and have been described as invariably fatal. The pathogenesis of this disorder is poorly understood, and no treatments are currently available. Methods/Case Report A 24 year old man with history of polysubstance abuse and untreated hepatitis C presented with acute abdominal pain. Imaging revealed hepatosplenomegaly and multiple liver, spleen, and skeletal lesions. Differential diagnoses included metastatic disease, lymphoma, and infection. Apart from known untreated chronic hepatitis C, all infectious, autoimmune and hypercoagulability work-ups were negative. Biopsies of the liver and iliac bone lesions showed areas of benign-appearing vascular proliferation in a background of fibrosis. The vascular endothelial cells were positive for CD34 and CD31 but negative for D2-40. On follow-up approximately eight months later, the patient was asymptomatic. Results (if a Case Study enter NA) NA Conclusion Liver involvement by cystic angiomatosis is exceedingly rare and has been associated with increased mortality. This case provides an example of a patient with incidentally discovered cystic angiomatosis involving liver, spleen, and bone who remains asymptomatic at follow-up. Additional cases are required to understand the pathophysiology and disease course in this group of patients, and to investigate possible therapeutic targets.

Cutaneous angiomatosis in a dog: a case report

A 1-year-old, castrated male mixed-breed dog presented with diffuse, purple lesions arranged in an irregular patchy pattern, with a slight elevation on the right hindlimb extending from the tarsus joint to the upper region of the thigh. Dermatological examinations and fungal and bacterial cultures revealed no infectious agents. The therapeutic response to antibiotics and antifungal agents was negative. A histopathology examination of the lesion revealed vascular proliferation with vasodilation and numerous varying-sized vessels. Mast-cell-dominated perivascular cuffing was also noted. The dog was diagnosed with cutaneous angiomatosis due to diffuse lesions and the histopathology findings of hemangioma.

Castleman lymphadenopathy: case review

Background. While examining regional lymph nodes removed with the tumor, the pathomorphologist is often limited to the exclusion of metastases, omitting changes in lymphoid tissue. The aim of the work is to describe a rare variant of Castleman-like lymphadenopathy in the surgical material obtained during the removal of colon cancer with regional lymph nodes. Methods. Pathomorphological examination of removed lymph nodes using histological and immunohistochemical methods (CD23). Results. A 73-year-old patient underwent surgery for rectal cancer. Pathomorphological analysis diagnosed adenocarcinoma of high degree of differentiation (G1) and revealed Castleman-like changes in some of the enlarged regional mesenteric lymph nodes: signs of different stages of development of lymphoid follicles, including their hyperplasia, atresia and fragmentation with preservation of activated CD23+ follicular dendritic cells and reaction of microvasculature, including vascular proliferation in the interfollicular areas with uneven narrowing of the sinuses. The discussion analyzes the probable genesis of changes in lymphoid tissue, which may be a reflection of the early stage of Castleman's disease, complication of radiation therapy performed in the preoperative stage, or a consequence of impaired immune status due to tumor growth, in particular with antigenic overloading of draining lymphoid tissue, effects of cytokines produced by inflammatory infiltrate cells that accumulate directly near the tumor, and the formation of a state of genetic instability, which progresses under the influence of radiation. Conclusion. Despite the rarity of Castleman-like lymphadenopathy, in each case of examination of lymph nodes in the surgical material it is necessary to conduct a thorough analysis of lymphoid tissue, as this may be important both to assess the prognosis and to select adequate therapy.

Pathomorphological Sequence of Nephron Loss in Diabetic Nephropathy

Following our reports on mesangial sclerosis and vascular proliferation in diabetic nephropathy (DN)(25,34) we now describe the advanced stages of DN terminating in glomerular obsolescence and tubulo-interstitial fibrosis based on a total of 918 biopsies. The structural aberrations emerge from two defects: First, an increased synthesis of glomerular basement membrane (GBM) components by podocytes and endothelial cells leading to an accumulation of GBM material in the mesangium. Second, a defect of glomerular vessels consisting of an increased leakiness and an increased propensity to proliferate. Both defects may lead to glomerular degeneration. The progressing compaction of the accumulated worn-out GBM-material together with the retraction of podocytes out of the tuft and the collapse and hyalinosis of capillaries results in a shrunken tuft that fuses with Bowman's capsule to glomerular sclerosis. The most frequent pathway to glomerular decay starts with local tuft expansions that result in contacts of structurally healthy podocytes to the parietal epithelium initiating the formation of tuft adhesions, which include the penetration of glomerular capillaries into BC. Exudation of plasma from such capillaries into the space between the parietal epithelium and its basement membrane causes the formation of insudative fluid accumulations within BC spreading around the glomerular circumference and, via the glomerulo-tubular junction, onto the tubule. Degeneration of the corresponding tubule develops secondarily to the glomerular damage, either due to cessation of filtration in cases of global sclerosis or due to encroachment of the insudative spaces. The degenerating tubules induce the proliferation of myo-fibroblasts resulting in interstitial fibrosis.