L’insuffisance rénale chronique (IRC) et l’une des pires maladies chroniques dans les pays développés. Les grades de l’IRC sont principalement basés sur la mesure ou l’estimation du taux de filtration rénale (GFR). Cependant, cette méthode est peu sensible sur les premiers stades de la pathologie et n’apporte donc pas de valeur diagnostique. La détection de la pathologie à des stades précoces et son traitement peuvent éviter ou limiter les effets délétères de la chronicité. Cette thèse se penche sur le développement de la microscopie IRTF en tant qu’outil diagnostic pour l’identification par histopathologie à l’échelle du glomérule dans un modèle d’IRC. Nous avons développé la technique de reconstruction 3D pour l’imagerie IRTF des modifications biochimiques à l’échelle du glomérule pour déterminer des marqueurs de l’IRC. La déconvolution spectrale et le clustering sont appliqués après analyses IRTF pour distinguer les modèles sains et pathologiques. Ensuite, la microvasculature glomérulaire est révélée par agent de contraste pour en déterminer les anomalies morphologiques. Grâce aux résultats obtenus en 3D et l’utilisation de méthodes statistiques avancées, la microscopie IRTF est utilisée comme une technique fonctionnelle pour déterminer les modifications morphologiques et moléculaires apparaissant au cours du développement de l’IRC. / CKD (Chronic Kidney Disease) is one of the worst public diseases in developing countries. The stages of CKD are mainly based on measured or estimated GFR (Glomerular Filtration Rate). However, this method is not sensitive enough on early stages of the pathology and thus do not offer accurate diagnostic value. Early detection and treatment can often limit or avoid the chronicity effects of the disease. This thesis focuses on the development of FTIR microscopy as a diagnostic tool for the identification by histopathology at glomerulus level of the kidney in CKD model. We developed a technique of 3D reconstruction for the FTIR imaging of biochemical components changes in glomeruli for identifying the pathological marker of CKD. The curve-fitting and spectral clustering are applied on the FTIR microscopy analysis to distinguish between healthy and pathological glomeruli of a kidney. Then, the glomerular microvasculatureis highlighted to reveal the morphological abnormalities by perfusing contrast agents into blood vessels. With advanced 3D statistical methods and 3D image visualization by microscopy, FTIR spectro-imaging can be used as a functional technique to determine the morphological and molecular changes occurring along CKD development.

<p>Meningioma represent more than one-third of all primary central nervous system (CNS) tumors,and it can be classified into three grades according to WHO (World Health Organization) in terms of clinical aggressiveness and risk of recurrence. A key component of meningioma grades is the mitotic count, which is defined as quantifying the number of cells in the process of dividing (i.e., undergoing mitosis) at a specific point in time. Currently, mitosis counting is done manually by a pathologist looking at 10 consecutive high-power fields (HPF) on a glass slide under a microscope, which is an extremely laborious and time-consuming process. The goal of this thesis is to investigate the use of computerized methods to automate the detection of mitotic nuclei with limited labeled data.We built computational methods to detect and quantify the histological features of mitotic cells on a whole slides image which mimic the exact process of pathologist workflow. Since we do not have enough training data from meningioma slide, we learned the mitotic cell features through public available breast cancer datasets, and predicted on meingioma slide for accuracy. We use either handcrafted features that capture certain morphological, statistical, or textural attributes of mitoses or features learned with convolutional neural networks (CNN). Hand crafted features are inspired by the domain knowledge, while the data-driven VGG16models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. Our work on detection of mitotic cells shows 100% recall, 9% precision and 0.17 F1 score. The detection using VGG16performs with 71% recall, 73% precision, and 0.77 F1 score.Finally, this research of automated image analysis could drastically increase diagnostic efficiency and reduce inter-observer variability and errors in pathology diagnosis, which would allow fewer pathologists to serve more patients while maintaining diagnostic accuracy and precision. And all these methodologies will increasingly transform practice of pathology, allowing it to mature toward a quantitative science.</p>

Objective: Celecoxib (CEL) is a nonsteroidal anti-inflammatory drug (NSAID) showing selective cycloxygenase-2 inhibition. While effective as a pain reducer, CEL exerts some negative influence on renal and gastrointestinal parameters. This study examined CEL pharmacodynamics and pharmacokinetics following drug reformulation as a poly(lactic-co-glycolic) acid nanoparticle (NP). Materials and Methods: Rats were administered either vehicle (VEH) (methylcellulose solution), blank NP, 40 mg/kg CEL in methylcellulose, or an equivalent NP dose (CEL-NP). Plasma and urine (over 12 hrs) samples were collected prior to and post-treatment. The mean percent change from baseline of urine flow rate along with electrolyte concentrations in plasma and urine were assessed based on 100 g body weight. Using tissues collected 24 hrs post-treatment, gastrointestinal inflammation was estimated through duodenal and gastric prostaglandin E2 (PGE2) and duodenal myeloperoxidase (MPO) levels; while kidney tissue was examined for dilatation and necrosis. CEL concentration was assayed in renal tissue and plasma utilizing high-performance liquid chromatography. Results: Although there were significant changes when comparing CEL and CEL-NP to VEH in plasma sodium concentration and potassium excretion rate, there was no significant variation between CEL and CEL-NP. There was a significant reduction of protective duodenal PGE2 in CEL compared to VEH (p = 0.0088) and CEL-NP (p = 0 .02). In the C EL-NP formulation, t1/2, Cmax, AUC0-∞, and Vd/F increased significantly when compared to CEL. Conclusions: At the observed dosage and duration, CEL-NP may not affect CEL-associated electrolyte parameters in either plasma or urine; however, it does provide increased systemic exposure while potentially alleviating some gastrointestinal outcomes related to inflammation.

Nonsteroidal anti-inflammatory drugs (NSAIDs), non-selective or selective inhibitors of cyclooxygenase (COX-1 and -2), reduce pain and inflammation associated with arthritic diseases. Celecoxib, a COX-2-selective inhibitor providing decreased gastric injury relative to non-selective NSAIDs, is commonly prescribed. Misoprostol, a prostaglandin analog, supplements NSAID-inhibited prostaglandin levels. As concomitant celecoxib and misoprostol administration has been shown to intensify renal adverse effects, this article examined the influence of concomitant administration on hepatic histopathology, oxidative stress, and celecoxib concentration. On days 1 and 2, rat groups (n = 6) were gavaged twice daily (two groups with vehicle and two groups with 100 μg/kg misoprostol). From day 3 to day 9, one celecoxib dose (40 mg/kg) replaced a vehicle dose of one group and one group received celecoxib in addition to misoprostol. Livers were harvested on day 10. No hepatic abnormalities were observed denoting a lack of influence by either drug. Also no change in mean biomarker levels was detected. The changes in hepatic celecoxib concentration in the misoprostol-receiving group compared to control were not significant. Thus misoprostol does not influence hepatic celecoxib effects in terms of histopathology, oxidative stress, or celecoxib concentration level at the dosage and duration examined.

INTRODUCTION: Ebola virus (EBOV) is a highly infectious and often lethal filovirus that causes hemorrhagic fever, with a reported case fatality rate of 40-90%. There are currently no Food and Drug Administration (FDA) approved medical countermeasures (MCMs) for EBOV. Non-human primates (NHPs) remain the gold standard animal model for EBOV research as they most accurately recapitulate human disease. OBJECTIVE: This study aimed to characterize the temporal viral pathogenesis of EBOV in the liver of infected rhesus macaques using routine histopathology, multiplex immunohistochemistry (mIHC) and multiplex fluorescent In Situ Hybridization (mFISH), refined by digital pathology (DP) and image analysis (DIA). METHODS: 21 FFPE liver sections from EBOV-infected rhesus macaques were examined microscopically (Uninfected controls n=3; 3 DPE n=3; 4 DPE n=3; 5 DPE n=3; 6 DPE n=3; Terminal n=6). Tissues were stained with H&E and PTAH for histopathological scoring. Three serial sections were fluorescently immunolabeled or hybridized under three independent conditions (1.EBOV VP35, Tissue Factor, CD68; 2.EBOV VP35, Heppar, Myeloperoxidase (MPO); 3.EBOV VP35, IL-6, ISG-15). Slides were digitized by a Vectra PolarisTM fluorescent whole slide scanner and DIA was conducted using HaloTM image analysis software. Statistical analysis was conducted using GraphPad PrismTM 8.0. RESULTS: Comparing peracute (3-4 DPE) to acute (5-6 DPE) and terminal (6-8 DPE) EBOV infection, there is a statistically significant (p < 0.05) increase in hepatic inflammation and fibrin thrombi, correlating with an absolute increase in macrophages (CD68), neutrophils (MPO), and total % of Tissue Factor in the liver. There is also a significant increase in the severity of necrosis, which correlates with a decrease in Heppar. While there was significant colocalization of VP35 and CD68 starting at 4 DPE, there was only rare colocalization of VP35 with Heppar, even in terminal animals. Similar to mIHC, progressive and statistically significant differences were observed in gene expression when comparing peracute to acute and terminal EBOV infection. IL-6 predominated within periportal fibrovascular compartments, but also colocalized within cells concurrently expressing EBOV VP35. EBOV VP35 expression was observed within histiocytes, endothelial cells, and less commonly hepatocytes. ISG-15 expression was observed in periportal regions and in proximity to cells expressing EBOV VP35, but colocalization within EBOV VP35 expressing cells was an extremely rare event. CONCLUSION: Qualitative tools are well suited for confirming virulence and viral tissue tropism, but do little to build on our current understanding of disease. Using DIA in partnership with mIHC and mFISH, this study quantified statistically significant temporal changes in the immunoreactivity and hybridization of host and viral biomarkers that have previously been linked to the pathogenesis of EBOV. Taken together, these tools have enabled us to characterize minute changes that reflect magnitudes of biological variability simply not feasible to detect with the human eye. Furthermore, spatial context has refined our current understanding of differential gene expression of EBOV, which has the potential to aid in development of host-directed therapies. The establishment of these benchmarks will serve as a guide for the validation of cross-institutional EBOV animal models.

No description available.

AIM/PURPOSE: To investigate the correlation between the histopathology of periapical lesion of endodontic origin and the radiographic findings of the maxillary sinus observed by cone-beam computed tomography (CBCT). MATERIAL AND METHODS: Retrospective record review study, data collected of patients received surgical root canal treatment at Boston University school of dental medicine. Total of 39 periapical lesions all had CBCT scans and pathology reports. Each periapical lesion was biopsied and examined by oral & maxillofacial pathologist. CBCT scans for each lesion were examined by two examiners: endodontic resident and board-certified endodontic faculty. RESULTS: 65% of the lesions associated with changes in the maxillary sinus and 35% had no changes as seen on the CBCT scans. 82% of the lesions were granulomas 15.5% were cysts and 2.5% OKC. Out of the 65% (26 lesions) maxillary sinus changes were 50% (13) were periapical mucositis (PAM) & 50% (13) were periapical osteoperiostitis (PAO). CONCLUSION: Histopathology of the periapical lesion didn’t have an effect on the type of changes observed in the sinus. And the closer the lesion was to the sinus the more chances of developing changes in the sinus.

Yes / There is increasing interest in the use of artificial intelligence (AI) in pathology to increase accuracy and efficiency. To date, studies of clinicians' perceptions of AI have found only moderate acceptability, suggesting the need for further research regarding how to integrate it into clinical practice. The aim of the study was to determine contextual factors that may support or constrain the uptake of AI in pathology. To go beyond a simple listing of barriers and facilitators, we drew on the approach of realist evaluation and undertook a review of the literature to elicit stakeholders' theories of how, for whom, and in what circumstances AI can provide benefit in pathology. Searches were designed by an information specialist and peer-reviewed by a second information specialist. Searches were run on the arXiv.org repository, MEDLINE, and the Health Management Information Consortium, with additional searches undertaken on a range of websites to identify gray literature. In line with a realist approach, we also made use of relevant theory. Included documents were indexed in NVivo 12, using codes to capture different contexts, mechanisms, and outcomes that could affect the introduction of AI in pathology. Coded data were used to produce narrative summaries of each of the identified contexts, mechanisms, and outcomes, which were then translated into theories in the form of context-mechanism-outcome configurations. A total of 101 relevant documents were identified. Our analysis indicates that the benefits that can be achieved will vary according to the size and nature of the pathology department's workload and the extent to which pathologists work collaboratively; the major perceived benefit for specialist centers is in reducing workload. For uptake of AI, pathologists' trust is essential. Existing theories suggest that if pathologists are able to "make sense" of AI, engage in the adoption process, receive support in adapting their work processes, and can identify potential benefits to its introduction, it is more likely to be accepted. For uptake of AI in pathology, for all but the most simple quantitative tasks, measures will be required that either increase confidence in the system or provide users with an understanding of the performance of the system. For specialist centers, efforts should focus on reducing workload rather than increasing accuracy. Designers also need to give careful thought to usability and how AI is integrated into pathologists' workflow.

This study was conducted to compare the gizzard integrity between two broilers flocks, one under a no antibiotics ever (NAE) program and the other from a conventionally raised flock (CONV). One-hundred Ross 708 x Ross YPM broiler chickens from two flocks of the same company but raised under two distinct management systems were allocated for this study. At 1, 14, 28 and 42 days of age, birds from both flocks were received at the Poultry Research and Diagnostic Laboratory. Gross and histopathologic evaluations of gizzard lesions and microbiological determinations of the gizzard mucosa were conducted and body and gizzard weights were recorded. Birds under both programs showed very similar growth rates, however gizzards were heavier in the birds under the CONV program. The birds under the NAE program had higher gross gizzard lesion scores at days 1, 14, 28 and 42, with statistical significance at day 42 (P<0.05). Histopathologically, the birds under the NAE program had greater gizzard lesion scores compared to the CONV flock at days 14 and 28, however no statistical significance was established. Escherichia coli was more frequently isolated from the birds under the CONV program. According to these observations, gross and microscopic gizzard lesions appeared to be more associated with the NAE program.

No description available.