Tissue Pathology Research Articles

Transcriptome RNA-Seq Analysis of Normal and Keratoconus Corneal Epithelium

Background: Keratoconus (KTCN) is a progressive eye condition characterised by thin, misshapen corneas arising in the teens or early twenties, and can cause visual disability. While this can be corrected with glasses or contact lenses, collagen cross-linking of the cornea slows disease progression. In advanced disease, patients undergo transplantation of the corneal epithelial layer with normal donor tissue. The cause of KTCN is unknown, but there is evidence for both environmental and genetic bases. Material and Methods: RNA-Seq data from published work by Kabza et al., 2017, was used to investigate the pathology of cornea tissue, analysing twenty-five KTCN and twenty-five non-KTCN samples from RNA-seq experiments. Principal component analysis plots were used to identify how characteristics impact development of keratoconus. Results: The findings show that KTCN is more common in teenagers and young adults, and all 25 KTCN samples were for individuals under 30 years old. Principal component analysis also showed that approximately 35% of samples were from individuals who rubbed their eyes. It also showed that KTCN is more common in males, representing over 65% of samples. Differential expression analysis of RNA-sequencing data was used to identify differentially expressed genes, downregulated genes were found to be enriched in many pathways, including cytokinecytokine receptor interaction pathways, and played a role in keratoconus development. Conclusion: Upregulated genes were enhanced in six pathways, including the peroxisome pathway. A potential relation was found between defects in peroxisome and keratoconus development. Overexpression of peroxisome genes increases phytanic acid levels, and causes Zellweger spectrum, affecting the cornea and potentially leading to keratoconus.

Multi-element analysis of metals in human pathological and unchanged thyroid glands - pilot study.

Disturbances in the homeostasis of the elemental composition of thyroid tissue may have serious metabolic and health consequences. It is believed that the accumulation of some metals or the deficiency of others may even cause lethal tumours. Due to the fact that metallomics most often uses human serum to analyse macro and microelements as well as trace elements, it was decided to use material that is more difficult to obtain, but also adds credibility to the research - thyroid tissue samples biopsy. The experiments were conducted on 17 patients diagnosed with: nodular (10) and colloidal goitre (2), chronic thyroiditis (2), follicular adenoma (2) and papillary carcinoma (1). They were recruited by collecting a tumour fragment, control fragment and serum from each of them. The content of Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Zn was examined using ICP-OES (Inductively Coupled Plasma - Optical Emission Spectrometers). Simultaneously, biochemical methods were used to determine the markers of inflammation, glycation and peroxidation: malondialdehyde, pentosidine, reactive free amine content, compounds with thiol groups and galectin 3 in the sera of the examined patients. Three statistically significant correlations were identified: Ca-Mg and Cu-Zn in control tissues (p < 0.05) and Cr-Mn in pathological tissues (p < 0.05). A comparison of individual groups of patients shows that there are some potentail tendencies to increase or decrease in the concentration of certain elements or markers of inflammation and glycation, therefore we discuss potential relationships between a given parameter and a thyroid disorder. The pilot study is an introduction to a deeper analysis aimed at tracing the pathomechanism of the development of thyroid diseases, so that the risk of developing these diseases can be effectively minimized.

Curvature-mediated rapid extravasation and penetration of nanoparticles against interstitial fluid pressure for improved drug delivery

Elevated interstitial fluid pressure (IFP) within pathological tissues (e.g., tumors, obstructed kidneys, and cirrhotic livers) creates a significant hindrance to the transport of nanomedicine, ultimately impairing the therapeutic efficiency. Among these tissues, solid tumors present the most challenging scenario. While several strategies through reducing tumor IFP have been devised to enhance nanoparticle delivery, few approaches focus on modulating the intrinsic properties of nanoparticles to effectively counteract IFP during extravasation and penetration, which are precisely the stages obstructed by elevated IFP. Herein, we propose an innovative solution by engineering nanoparticles with a fusiform shape of high curvature, enabling efficient surmounting of IFP barriers during extravasation and penetration within tumor tissues. Through experimental and theoretical analyses, we demonstrate that the elongated nanoparticles with the highest mean curvature outperform spherical and rod-shaped counterparts against elevated IFP, leading to superior intratumoral accumulation and antitumor efficacy. Super-resolution microscopy and molecular dynamics simulations uncover the underlying mechanisms in which the high curvature contributes to diminished drag force in surmounting high-pressure differentials during extravasation. Simultaneously, the facilitated rotational movement augments the hopping frequency during penetration. This study effectively addresses the limitations posed by high-pressure impediments, uncovers the mutual interactions between the physical properties of NPs and their environment, and presents a promising avenue for advancing cancer treatment through nanomedicine.

Microglia, Trem2, and Neurodegeneration.

Microglia are a specialized type of neuroimmune cells that undergo morphological and molecular changes through multiple signaling pathways in response to pathological protein aggregates, neuronal death, tissue injury, or infections. Microglia express Trem2, which serves as a receptor for a multitude of ligands enhancing their phagocytic activity. Trem2 has emerged as a critical modulator of microglial activity, especially in many neurodegenerative disorders. Human TREM2 mutations are associated with an increased risk of developing Alzheimer disease (AD) and other neurodegenerative diseases. Trem2 plays dual roles in neuroinflammation and more specifically in disease-associated microglia. Most recent developments on the molecular mechanisms of Trem2, emphasizing its role in uptake and clearance of amyloid β (Aβ) aggregates and other tissue debris to help protect and preserve the brain, are encouraging. Although Trem2 normally stimulates defense mechanisms, its dysregulation can intensify inflammation, which poses major therapeutic challenges. Recent therapeutic approaches targeting Trem2 via agonistic antibodies and gene therapy methodologies present possible avenues for reducing the burden of neurodegenerative diseases. This review highlights the promise of Trem2 as a therapeutic target, especially for Aβ-associated AD, and calls for more mechanistic investigations to understand the context-specific role of microglial Trem2 in developing effective therapies against neurodegenerative diseases.

Экспериментальные исследования акустического поля поперечных волн в модели биологической ткани

This article develops the ultrasound diagnostics principles using elastography technology and presents the experimental setup diagram. Biological tissue is modeled using silicone material. Research has been carried out and the longitudinal and transverse sound speeds have been determined. Further research will create a database of pathological and healthy tissues various samples.

Supervised latent factor modeling isolates cell-type-specific transcriptomic modules that underlie Alzheimer’s disease progression

Late onset Alzheimer’s disease (AD) is a progressive neurodegenerative disease, with brain changes beginning years before symptoms surface. AD is characterized by neuronal loss, the classic feature of the disease that underlies brain atrophy. However, GWAS reports and recent single-nucleus RNA sequencing (snRNA-seq) efforts have highlighted that glial cells, particularly microglia, claim a central role in AD pathophysiology. Here, we tailor pattern-learning algorithms to explore distinct gene programs by integrating the entire transcriptome, yielding distributed AD-predictive modules within the brain’s major cell-types. We show that these learned modules are biologically meaningful through the identification of new and relevant enriched signaling cascades. The predictive nature of our modules, especially in microglia, allows us to infer each subject’s progression along a disease pseudo-trajectory, confirmed by post-mortem pathological brain tissue markers. Additionally, we quantify the interplay between pairs of cell-type modules in the AD brain, and localized known AD risk genes to enriched module gene programs. Our collective findings advocate for a transition from cell-type-specificity to gene modules specificity to unlock the potential of unique gene programs, recasting the roles of recently reported genome-wide AD risk loci.

Does larger prostate size provide protection for cancer specific outcomes in localized prostate cancer.

Benign prostatic hyperplasia is common in the aging population and frequently comorbid with localized prostate cancer. Large prostate volume places significant challenges in robotic prostatectomy including reduced mobility and visualization. The goal of this study is to evaluate the effect of prostate volume as a continuous variable on cancer specific outcomes. Three thousand four hundred and twenty five patients with localized prostate cancer at a single institution who underwent robotic prostatectomy were retrospectively reviewed. A number of preoperative, operative, and postoperative variables were collected to evaluate cancer specific outcomes including pathologic stage, tissue margins, and biochemical recurrence (BCR). Logistic regression models and univariate and multivariate analyses were implemented for pathologic stage T3 and BCR respectively. The median follow up time was 52 months (IQR 18-95). 37.4% of the patients had a final pathologic stage of T3 or higher, 21.2% experienced positive surgical margins, and 24.7% of patients experienced BCR. Prostate size was a significant predictor of all three outcomes of interest. Increasing prostate size was protective against both higher pathologic stage and positive surgical margins (odds ratio = 0.989, 0.990 respectively, p < 0.001). There was a modest increase in the risk of BCR with increasing gland size (hazard ratio = 1.006, p < 0.001). These results were most significant for patients with Gleason Grade Groups 1 and 2 prostate cancer. Prostate size is a commonly determined clinical factor that effects both surgical planning and cancer specific outcomes. Increasing prostate size may offer protection against higher stage disease and positive surgical margins. While surgically challenging, favorable oncologic outcomes can be consistently achieved for patients with low-intermediate risk disease.

Histologic Hitchhikers: A Review of Common Exogenous Artifacts Encountered During Mohs Micrographic Surgery.

Exogenous artifacts can interfere with accurate histologic tissue evaluation on frozen sections during Mohs micrographic surgery (MMS). Mohs surgeons should be aware of these anomalies to avoid potential misdiagnoses. To review exogenous artifacts encountered in frozen tissue pathology during MMS. A literature search was conducted in PubMed to identify studies reporting on exogenous artifacts encountered during MMS and a list of previously described exogenous artifacts was compiled. A retrospective examination of frozen histology slides from recent Mohs cases at the authors' institution was performed to obtain illustrative examples of these artifacts, supplemented by formalin-fixed paraffin-embedded samples when frozen examples could not be found. Exogenous artifacts represent foreign bodies that have been externally introduced into the skin or artifacts resulting from other external factors. If frozen section evaluation is inaccurate, overdiagnosis can occur during MMS, resulting in unnecessary layers, larger margins, and more complex reconstructions. These exogenous tissue changes can mimic inflammatory processes and melanocytic or keratinocyte malignancies on histology. Exogenous artifacts are common findings during margin assessment in Mohs micrographic surgery. The resulting histological findings can be confusing but correlating them with the clinical and surgical history often reassures surgeons. Recognizing these artifacts facilitates accurate diagnosis and promotes optimal patient care.

3D bioartificial stretchable scaffolds mimicking the mechanical hallmarks of human cardiac fibrotic tissue

Human cardiac fibrotic tissues are characterized by a higher stiffness relative to healthy cardiac tissues. These tissues are unable to spontaneously contract and are subjected to passive mechanical stimulation during heart functionality. Moreover, scaffolds that can recapitulate the in vivo mechanical properties of the cardiac fibrotic tissues are lacking. Herein, this study aimed to design and fabricate mechanically stretchable bioartificial scaffolds with biomimetic composition and stiffness comparable to human cardiac fibrotic tissues. Poly(&amp;epsilon;-caprolactone) (PCL) scaffolds with a stretchable mesh architecture were initially designed through structural and finite element method (FEM) analyses and subsequently fabricated by melt extrusion additive manufacturing (MEX). Scaffolds were surface functionalized by 3,4-dihydroxy-DL-phenylalanine (DOPA) polymerization (polyDOPA) to improve their interaction with natural polymers. Scaffold pores were then filled with different concentrations (5%, 7%, and 10% w/v) of gelatin methacryloyl (GelMA) hydrogels to support in vitro human cardiac fibroblasts (HCFs) 3D culture, thereby producing bioartificial PCL/GelMA scaffolds. Uniaxial tensile mechanical tests in static and dynamic conditions (1 Hz; 22% maximum strain) demonstrated that the bioartificial scaffolds had in vivo-like stretchability and similar stiffness to that of pathological cardiac tissue (tailored as a function of the number of PCL scaffold layers and GelMA hydrogel concentration). In vitro cell tests on bioartificial scaffolds using HCF-embedded GelMA hydrogels under static conditions displayed increasing cell viability, spreading, and cytoskeleton organization with decreasing GelMA hydrogel concentration. Moreover, &amp;alpha;-smooth muscle actin (&amp;alpha;-SMA)-positive cells were detected after 7 days of culture in static conditions followed by another 7 days of culture in dynamic conditions and not in HCF-loaded scaffolds cultured in static conditions for 14 days. These results suggested that in vitro culture under cyclic mechanical stimulations could induce an HCF phenotypic switch into myofibroblasts.

The categorization of opaque pathologies outside of contrast media in hysterosalpingography which facilitate interpretation: A pictorial review

Hysterosalpingography (HSG) is a practical and reliable imaging method to evaluate the cervical canal, uterine isthmus, uterine cavity, and fallopian tubes. Using HSG, opaque pathologies outside of contrast media can be detected as well as pathologies of uterus and fallopian tubes. We aim to present and categorize some uncommon and interesting abnormal findings that are located outside of the contrast areas in HSG. This is a pictorial review that depicts various types of HSG images that include opaque pathologies outside of the contrast areas. Images have been extracted from valuable archives collected over 50 yr by professor Shahrzad. A plain pelvic film contains soft tissues of the pelvis, bony structures, artifacts, or foreign bodies. Categorization might easily help the radiologist to interpret the HSG cliché. Opaque pathologies outside of contrast area in HSG can be categorized into 2 groups: “Pelvic Tissue Related” and “Foreign Bodies”. Pelvic tissue abnormalities might have a gynecologic or nongynecologic source. Foreign bodies can be located in the pelvis or outside of the body. HSG is a reliable and inexpensive procedure. Familiarity with the pathologies of pelvic tissues and the accurate interpretation of HSG images are important. Key words: Hysterosalpingography, Opaque, Abnormalities, Uterine, Fallopian tubes.

Advances in the prerequisite and consequence of STING downstream signalosomes

Abstract The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is an evolving DNA-sensing mechanism involved in innate immunity and pathogen defense that has been optimized while remaining conserved. Aside from recognizing pathogens through conserved motifs, these receptors also detect aberrant or misplaced self-molecules as possible signs of perturbed homeostasis. Upon binding external or self-derived DNA, a mobile secondary messenger 2′3′-cyclic GMP-AMP (cGAMP) is produced by cGAS and in turn activates its adapter STING in the endoplasmic reticulum (ER). Resting-state or activated STING protein is finely restricted by multiple degradation machineries. The post-translational changes of the STING protein, along with the regulatory machinery of the secret routes, limit the onset, strength and sustention of STING signal. STING experiences a conformational shift and relocates with TBK1 from the ER to perinuclear vesicles containing transcription factors, provoking the transcription activity of IRF3/IFN-I and NF-κB pathways, as well as to initiate a number of cellular processes that have been shown to alter the immune landscape in cancer, such as autophagy, NLRP3 inflammasome, ER stress, and cell death. STING signal thus serves as a potent activator for immune mobilization yet also triggers immune-mediated pathology in tissues. Recent advances have established the vital role of STING in immune surveillance as well as tumorigenic process. This review provides an overview of the disparate outcomes of cancer attributed to the actions of pleiotropic and coordinated STING downstream signalosomes, along with the underlying mechanisms of STING function in pathologies, providing therapeutic implications for new approaches in hunt for the next generation of cancer immunotherapy base on STING.

Identification of diffusion, kurtosis, and propagator MRI markers of Alzheimer’s disease pathology in post-mortem human tissue

Abstract Alzheimer’s disease (AD) is an irreversible degenerative brain disease affecting 6.7 million Americans and while the hallmark AD pathologies of plaques and tangles follow a stereotyped progression during the course of the disease, clinical markers for early diagnosis are lacking and approximately 20% of all AD cases are ultimately misdiagnosed. Conventional clinical MRI is capable of reporting severe brain atrophy, but fails to recognize earlier biomarkers associated with more subtle cellular and molecular changes. Microstructural Magnetic Resonance Imaging (MRI) techniques are promising to address this challenge and may sensitively detect and distinguish tissue degeneration, tauopathies, and beta amyloid plaques to improve accuracy of diagnosis and enable early detection. The objective of this study was to identify and compare the most promising microstructural markers of AD pathology over a range of diffusion and relaxometry-based MRI techniques from conventional to advanced. To accomplish this, we performed MRI microscopy of post-mortem human temporal lobe specimens (n = 14) at high resolution and image quality and evaluated the relative influence of metrics across multiple microstructural MRI frameworks using principal component analysis (PCA). We performed additional correlation analysis between metrics identified by PCA and clinical neuropathology scores of Braak stage and plaque and tangle load. Hippocampal diffusion and restriction metrics contributed most to the first principal component, and the correlation with Braak score was positive for diffusivity and negative for restriction metrics. Additionally, the MAP-MRI propagator anisotropy (PA) metric of microscale anisotropy was strongly and negatively correlated with AD pathology while the conventional fractional anisotropy (FA) metric showed little or no correspondence and there was not a strong association between FA and PA by PCA. Entorhinal cortex findings were minimal except for reported increases in restriction due to plaque content. Taken together, our findings suggest that microstructural MRI metrics of restriction and diffusion are most prominent and may reflect degenerative processes in AD brain tissue and that microscale anisotropy may be more advantageous than conventional FA for the detection of subtle and earlier cellular changes in AD.

Feasibility of high-frequency ultrasound for seminiferous tubule assessment and correlation of B-mode imaging with pathological findings in the testis in azoospermia.

To determine the feasibility of high-frequency ultrasound (HFUS) for assessing seminiferous tubules and to understand high-resolution B-mode images of the testes in cases of azoospermia. We verified how the histopathological images of testicular biopsy specimens can be observed using HFUS images and measurement analysis of seminiferous tubules was performed to 28 testes of 14 cases with azoospermia who underwent preoperative ultrasound and microdissection testicular sperm extraction (micro-TESE). The population consisted of obstructive azoospermia (OA) and non-obstructive azoospermia (NOA), including Sertoli cell-only syndrome (SCOS), and the other pathologies. Statistical verification of differences in seminiferous tubule diameters among preoperative ultrasound examination, ultrasound examination of pathological specimens, and histopathological specimens. We also examined the imagingpathology correlation via a case series presentation, aiming to identify imaging markers of testicular pathology and determine the possibility of predicting each condition. A comparison between HFUS images and histopathology from the same biopsy specimens suggested that ultrasonography could be seen as stereoscopic images due to its significantly greater slice thickness. The diameters of tubules were generally larger in pathological tissues as compared to ultrasonographic findings in OA and SCOS, but not in the other conditions. Comparisons provided insights into the predictability of SCOS and revealed imaging findings such as gaps between tubules and decreased diameter reflective of testicular damage. Seminiferous tubules can be observed however the diameter of seminiferous tubules varies in imaging and histopathology depending on the pathology. Imaging findings that reflect testicular damage and the predictability of SCOS were revealed in this study, but further verification is required.

Monoclonal Antibodies Against Mature Interleukin-18 Ameliorate Colitis and Repair Goblet Cell Function.

Numerous biological interventions and small molecules are used to treat Crohn's disease; however, the effectiveness of these treatments varies largely. Non-responsiveness to biological therapies is associated with interleukin (IL)-18 gene polymorphisms and high IL-18 expression has been implicated in the pathogenesis of Crohn's disease. The aim of this study was to elucidate the expression of precursor and mature IL-18 in patients with Crohn's disease who exhibited varied responses to cytokine-targeted treatments and determine whether selective inhibition of mature IL-18 offers a novel therapeutic avenue. We generated a monoclonal antibody that specifically recognizes the neoepitope of caspase-cleaved mature IL-18. Expression of precursor and mature IL-18 was analyzed in patients with Crohn's disease. Anti-mature IL-18 monoclonal antibodies were intraperitoneally administered in an acute colitis mouse model, and the disease activity index, body weight loss, tissue pathology, proinflammatory cytokine expression, goblet cell function, and microbiota composition were assessed. Precursor and mature IL-18 expression was upregulated and goblet cell function was impaired in patients with Crohn's disease who were unresponsive to biological therapies. Administration of anti-mature IL-18 antibodies ameliorated induced colitis by repairing goblet cell function and restoring the mucus layer. The newly developed monoclonal antibody holds promise as a therapeutic alternative for Crohn's disease.

Inhibition of caspase pathways limits CD4+ T cell loss and restores host anti-retroviral function in HIV-1 infected humanized mice with augmented lymphoid tissue.

The study of HIV infection and pathogenicity in physical reservoirs requires a biologically relevant model. The human immune system (HIS) mouse is an established model of HIV infection, but defects in immune tissue reconstitution remain a challenge for examining pathology in tissues. We utilized exogenous injection of the human recombinant FMS-like tyrosine kinase 3 ligand (rFLT-3L) into the hematopoietic stem cell (HSC) cord blood HIS mouse model to significantly expand the total area of lymph node (LN) and the number of circulating human T cells. The results enabled visualization and quantification of HIV infectivity, CD4 T cell depletion and other measures of pathogenesis in the secondary lymphoid tissues of the spleen and LN. Treatment with the Caspase-1/4 inhibitor VX-765 limited CD4+ T cell loss in the spleen and reduced viral load in both the spleen and axillary LN. In situ hybridization further demonstrated a decrease in viral RNA in both the spleen and LN. Transcriptomic analysis revealed that in vivo inhibition of caspase-1/4 led to an upregulation in host HIV restriction factors including SAMHD1 and APOBEC3A. These findings highlight the use of rFLT-3L to augment human immune system characteristics in HIS mice to support investigations of HIV pathogenesis and test host directed therapies, though further refinements are needed to further augment LN architecture and cellular populations. The results further provide in vivo evidence of the potential to target inflammasome pathways as an avenue of host-directed therapy to limit immune dysfunction and virus replication in tissue compartments of HIV+ persons.

ИЗМЕНЕНИЕ БИОТИПА ДЕСНЫ В ПРОЕКЦИИ ДЕНТАЛЬНЫХ ИМПЛАНТАТОВ

Deficiency of keratinized gum in the peri-implant zone contributes to bone recession and visualization of implant necks and abutments through its thin layer. To develop clinically effective and scientifically based protocols for the prevention and treatment of pathology of tissues surrounding implants, it is necessary to study the risk factors for the occurrence of mucositis and peri-implantitis, one of which is the deficiency or complete absence of attached keratinized gum in the implant area, as a result of which the mobile mucous membrane is constantly displaced during eating, talking, performing hygiene procedures. The gums are easily injured, which leads to rapid colonization of pathogenic microflora and the development of initial inflammation in the form of mucositis. The inflammatory process is launched, which in turn leads to an increase in the activity of osteoclasts. It should be noted that the rate of development of the inflammatory process in the area of implants is much higher than in the area of teeth. Due to the absence of the periodontal ligament, the inflammatory infiltrate directly spreads to the alveolar bone and penetrates into the medullary spaces. The gum contour in the area of installed implants must be aesthetic, stable and dense. This together will not only provide a cosmetic effect, but will also prevent the development of early and late complications of dental implantation. The paper provides an analysis of various methods of mucogingival surgery in the field of dental implants using an allogeneic graft of the “Alloplant” series. Engraftment of mucosal autografts from the tubercle of the upper jaw after surgery is accompanied by severe inflammation, which can lead to scarring of the mucosa or exposure of the bone. Allografts transplanted to patients to thicken the gums in the area of implantation are completely replaced after 6 months without signs of rejection or inflammatory processes by a full-fledged connective tissue regenerate covered with stratified squamous keratinizing epithelium. In the surgical area, gum tissue is formed in thickness, which can be classified as a “thick” gum phenotype.

In vivo disentanglement of diffusion frequency-dependence, tensor shape, and relaxation using multidimensional MRI.

Diffusion MRI with free gradient waveforms, combined with simultaneous relaxation encoding, referred to as multidimensional MRI (MD-MRI), offers microstructural specificity in complex biological tissue. This approach delivers intravoxel information about the microstructure, local chemical composition, and importantly, how these properties are coupled within heterogeneous tissue containing multiple microenvironments. Recent theoretical advances incorporated diffusion time dependency and integrated MD-MRI with concepts from oscillating gradients. This framework probes the diffusion frequency, , in addition to the diffusion tensor, , and relaxation, , , correlations. A clinical imaging protocol was then introduced, with limited brain coverage and 3 mm3 voxel size, which hinder brain segmentation and future cohort studies. In this study, we introduce an efficient, sparse in vivo MD-MRI acquisition protocol providing whole brain coverage at 2 mm3 voxel size. We demonstrate its feasibility and robustness using a well-defined phantom and repeated scans of five healthy individuals. Additionally, we test different denoising strategies to address the sparse nature of this protocol, and show that efficient MD-MRI encoding design demands a nuanced denoising approach. The MD-MRI framework provides rich information that allows resolving the diffusion frequency dependence into intravoxel components based on their distribution, enabling the creation of microstructure-specific maps in the human brain. Our results encourage the broader adoption and use of this new imaging approach for characterizing healthy and pathological tissues.

Experimental Animal Models of Periodontal Diseases

Abstract Periodontal diseases involve several conditions that are defined by pathologic loss of the periodontal ligament and alveolar bone. Periodontitis is an inflammatory disease of periodontal tissue caused by a host immune response to dysbiotic microbial biofilm whose progression associated with destruction of tooth supporting tissue is promoted by host proteinases. Periradicular periodontitis is the most commonly diagnosed disease that affects the pathology of periodontal tissue in the area of the tooth root. This disease has also been described as apical periodontitis. Several experimental models of periodontal diseases have been developed in recent years. This paper provides an overview of experimentally induced animal models of periodontal disease (periodontitis and periradicular periodontitis) and the possibility of using different experimental animals to study aspects of periodontal disease, each with advantages and disadvantage.

Positron Emission Tomography with [18F]ROStrace Reveals Progressive Elevations in Oxidative Stress in a Mouse Model of Alpha-Synucleinopathy.

The synucleinopathies are a diverse group of neurodegenerative disorders characterized by the accumulation of aggregated alpha-synuclein (aSyn) in vulnerable populations of brain cells. Oxidative stress is both a cause and a consequence of aSyn aggregation in the synucleinopathies; however, noninvasive methods for detecting oxidative stress in living animals have proven elusive. In this study, we used the reactive oxygen species (ROS)-sensitive positron emission tomography (PET) radiotracer [18F]ROStrace to detect increases in oxidative stress in the widely-used A53T mouse model of synucleinopathy. A53T-specific elevations in [18F]ROStrace signal emerged at a relatively early age (6-8 months) and became more widespread within the brain over time, a pattern which paralleled the progressive development of aSyn pathology and oxidative damage in A53T brain tissue. Systemic administration of lipopolysaccharide (LPS) also caused rapid and long-lasting elevations in [18F]ROStrace signal in A53T mice, suggesting that chronic, aSyn-associated oxidative stress may render these animals more vulnerable to further inflammatory insult. Collectively, these results provide novel evidence that oxidative stress is an early and chronic process during the development of synucleinopathy and suggest that PET imaging with [18F]ROStrace holds promise as a means of detecting aSyn-associated oxidative stress noninvasively.

Under-reporting by surgical pathologists in tissue removed during revision surgery for metal-on-metal arthroplasties.

Although adverse local tissue reactions (ALTR) have been reported for metal-on-metal implants (MoM) requiring early revision surgery, no study has looked at the accuracy of surgical pathologists in diagnosing ALTR. This study aims to investigate the accuracy of reporting adverse local tissue reactions in tissue samples following revision surgery from metal-on-metal implants. The authors reviewed histology glass slides as well as the original pathology reports of tissue processed in revision arthroplasties in 23 cases. These samples were microscopically analyzed for tissue necrosis and cystic degeneration, the presence of metal particles, corrosion byproducts, membrane formation, histiocytic cells, lymphocytic cells, and vascular pathology. The authors' findings were then compared to their corresponding original pathology reports. The authors found consistent under-reporting of the tissue findings. Most importantly, 18 samples showed evidence of metal present compared to 2 samples on original pathology reporting. The authors found that 15 samples showed evidence of pathological membranous tissue compared to just 6 on original pathology reporting. While just 3 of the original pathology reports indicated the presence of areas of predominantly lymphocytic inflammatory cells, the authors found 13 examples of such areas. Although ALTR reactions have been described as a sequala of failed MoM, the authors' data suggest that ALTR may occur more frequently than previously described. Under-reported findings of ALTR deprive both the patient and orthopaedic surgeon of important information that can help guide further follow-up.