CD8+ Lymphocyte Infiltration is a Specific Feature of Colitis Induced By Immune Checkpoint Inhibitors

Background Immune checkpoint inhibitors (ICPIs) have revolutionized cancer therapy, although immune-related adverse events (irAEs) remain a severe issue. The clinical characteristics of colitis induced by ICPIs are very similar to inflammatory bowel disease. Recently, CD8+ lymphocyte infiltration into organs has been associated with the onset of irAEs. The present study compared the histological infiltration of CD8+ lymphocytes in irAE colitis with that in other colitis. Methods Among 102 newly diagnosed and untreated patients, 12 with irAE colitis, 37 with ulcerative colitis (UC), 22 with Crohn's disease (CD), and 31 with ischemic colitis (IC) were retrospectively enrolled. Biopsy specimens were obtained from endoscopic areas of high inflammation for immunohistochemical analysis of the number of CD4+ and CD8+ lymphocytes in the most inflamed high-powered microscopic field. Results In irAE colitis, CD8+ lymphocyte infiltration was significantly greater than that of CD4+ lymphocytes (p < 0.01). The amount of CD8+ lymphocyte infiltration was significantly higher in irAE colitis than in UC (p < 0.05), CD (p < 0.05), and IC (p < 0.01). The CD8+/CD4+ ratio was also significantly higher in irAE colitis (p < 0.01 vs. UC, CD, and IC, respectively). The optimal cut-off CD8+/CD4+ ratio for diagnosing irAE colitis was 1.17 (sensitivity: 83%, specificity: 84%). The optimal cut-off the number of CD8+ lymphocytes for diagnosing irAE colitis was 102 cells/high-power field (sensitivity: 75%, specificity: 81%). Conclusions Greater CD8+ lymphocyte infiltration and a higher CD8+/CD4+ ratio may be simple and useful biomarkers to distinguish irAE colitis from other forms of colitis.

Assessment of Nerve Repair Augmented with Adipose-Derived Mast Cells in an Animal Model

We aimed to analyze the involvement of adipose-sourced mast cells in nerve repair. Sixteen Wistar rats underwent complete transection of the sciatic nerves followed by either direct neurorrhaphy or neurorrhaphy and processed abdominal fat. Four animals were used as controls. Specimens were obtained at 4 and 10 weeks and analyzed using luxol fast blue stain, mast cell tryptase and CD34 (for angiogenesis) per microscopic field ×200. When assessed by luxol fast blue, normal nerves showed an average of 2–3 mast cells/field. At 4 weeks, there were 9.25 for the simple nerve sutures and 16 for the augmented repairs. At 10 weeks, there were 23 and 27.6. When assessed by mast cell tryptase, there were no positives in the controls. At 4 weeks, we found an average of 4 in the simple sutures and 2.5 in the augmented repairs. At 10 weeks, there were 4.5 and 0.2. In controls, there were 1–2 CD34+ blood vessels per field. At 4 weeks, simple repairs showed an average of 4 and, in those with adipose addition, 5.5. At 10 weeks, there were 7 and 12. Mechanically processed adipose tissue augmented nerve repair does not seem to increase mast cell expression but may support angiogenesis in an experimental model.

Ultrafast electron microscopy for probing magnetic dynamics

The spatial features of ultrafast changes in magnetic textures carry detailed information on microscopic couplings and energy transport mechanisms. Electrons excel in imaging such picosecond or shorter processes at nanometer length scales. We review the range of physical interactions that produce ultrafast magnetic contrast with electrons, and specifically highlight the recent emergence of ultrafast Lorentz transmission electron microscopy. From the fundamental processes involved in demagnetization at extremely short timescales to skyrmion-based devices, we show that ultrafast electron imaging will be a vital tool in solving pressing problems in magnetism and magnetic materials where nanoscale inhomogeneity, microscopic field measurement, non-equilibrium behavior or dynamics are involved. Graphic abstract

Feasibility of using tissue autolysis to estimate the postmortem interval in horses

Estimation of the postmortem interval (PMI) is a poorly studied field in veterinary pathology. The development of field-applicable methods is needed given that animal cruelty investigations are increasing continually. We evaluated various histologic criteria in equine brain, liver, and muscle tissue to aid the estimation of PMI in horses, which is central to forensic investigations of suspicious death. After death, autolysis proceeds predictably, depending on environmental conditions. Currently, no field-applied methods exist that accurately estimate the PMI using histology in animals or humans through quantification of autolysis. Brain, liver, and skeletal muscle from 12 freshly euthanized horses were held at 22°C and 8°C for 72 h. Tissues were sampled at T0h, T1h, T2h, T4h, T6h, T12h, T24h, T36h, T48h, T60h, and T72h. For each tissue, we quantified 5 to 7 criteria associated with autolysis, based on the percentage of microscopic field involved. Each criterion was modeled, with temperature and time as independent variables. Changes were most predictable in liver and muscle over the first 72 h postmortem. The criteria for autolysis that were present most extensively at both temperatures were hepatocyte individualization and the separation of bile duct epithelium from the basement membrane. The changes that were present next most extensively were disruption of myofiber continuity, hypereosinophilia, and loss of striation. Brain changes were highly variable. The high statistical correlation between the parameter “autolysis” and the variables “time/temperature”, indicates that autolysis is progressive and predictable. Further investigation of these criteria is needed to establish histologic algorithms for PMI.

Performance of Daily Pads Containing Ophytrium and Chlorhexidine Digluconate 3% in Dogs With Local Cutaneous Bacterial and/or Malassezia Overgrowth

Local disturbances of the microbiota are common in dogs with underlying skin conditions. Antiseptic topical products are indicated to control such superficial disorders. The objective of this study was to evaluate the performance of a daily application of pads containing Ophytrium and chlorhexidine digluconate 3% (DOUXO® S3 PYO Pads, Ceva Santé Animale, France) in dogs with focal bacterial and/or Malassezia overgrowth. Eighteen dogs with focal skin dysbiosis were included in the analysis of this prospective, multicentric, field study. Dogs received daily pad applications for 14 days. Bacterial and/or Malassezia counts per microscopic field and a global score of the most affected patch (0–17 scale based on extension, severity, bacterial, and Malassezia cytological scores) were assessed by a veterinarian and pruritus by the owner (Pruritus Visual Analog Scale) on days (D)0, D7, D14. Owner and veterinarian evaluations for performance and satisfaction were recorded. Eleven dogs had primarily cocci overgrowth and seven mostly Malassezia. Mean bacterial and Malassezia counts decreased after 14 days (6.9–1.1; 7.6–1.5, respectively); 88.9% of dogs achieved a ≥70% microbial decrease and had ≤2 bacteria and ≤1 Malassezia per oil field. Mean global score of the most affected patch and pruritus score significantly improved at D14, respectively, from 8.6 to 2.6 and 4.5 to 1.2 (P &lt; 0.05 each, mean improvements of 70.4 and 71.4%, respectively). Global veterinary assessment of the protocol was satisfactory, good, or excellent in 88.9% of cases. Most owners (94.4%) considered the protocol efficacious. Using a pad containing Ophytrium and chlorhexidine digluconate 3% daily for 14 days improved the skin condition and pruritus of dogs with local dysbiosis, resulting in high satisfaction levels for both veterinarians and dog owners.

Comparative Histological study of Normal human placentae with Hypertensive placentae in Western part of Tamilnadu state (Kongunadu region)

Background: Placenta forms an intimate bonding between the mother and the foetus. Apart from gaseous exchange, transport of nutrients from mother to the foetus, any disease or disorder affecting the mother also reflects the foetus. Hypertension during antenatal period produces maternal vasospasm and vascular damage due to luminal constriction of uterine spiral arterioles causing histological changes in the placenta and ultimately leads to foetal hypoxia and death. Aim of the study: To compare the histological features between the normal and hypertensive placenta. Materials and Methods: 30 normal and 30 hypertensive placentae were collected, processed in the Department of Anatomy, Karpagam Faculty of Medical Sciences and Research, Coimbatore, Tamilnadu, and visualised under light microscope and their histological features are noted. Results: Various histological features obtained are Syncytial knots, Fibrinoid necrosis, Calcification of Placenta, Placental infarction, Stromal fibrosis, Hypovascularity of Villous, Intervillous fibrin deposition and Basement membrane thickening. Conclusion: In our study, the histological features are more prominent and their areas in microscopic field is noted more in hypertensive placentae than normal placentae.Histtological features are mainly due to maternal vasospasm and vascular endothelial injury.The statistical analysis calculated for the histological features was found to be significant. KEY WORDS: Placenta, Hypertension, Histology, Syncytial knots, Calcification.

Correlation between Tumour Associated Macrophage (TAM) Infiltration and Mitotic Activity in Canine Soft Tissue Sarcomas

Tumour-associated macrophages (TAMs) are an important part of the tumour microenvironment but knowledge of their distribution in canine soft tissue sarcomas (STSs) is limited to absent. We analysed 38 STSs retrieved from the veterinary pathology archive; oral and visceral STSs, synovial cell sarcoma, tumours of histiocytic origin, haemangiosarcoma, carcinosarcomas, and undifferentiated tumours were excluded. Iba-1 positive, non-neoplastic tumour infiltrating cells (morphologically indicative of macrophages) were classified as TAMs and were counted in 10 consecutive tumours areas, where no necrosis or other inflammatory cells could be identified. Associations between numbers of TAMs and mitoses, differentiation, and necrosis scores or grade were investigated. TAMs were evident in all STSs and ranged between 6% to 62% of the cells in the microscopic field. The number of TAMs positively correlated with the STSs’ histologic grade. When the components of the grade were analysed separately, TAMs were statistically correlated with mitoses, but not with differentiation or necrosis score. The present findings suggest that TAMs are present in higher numbers when STS proliferation is the predominant feature that drives tumour grade. The abundant presence of TAMs in high-grade STSs may also increase the likelihood of a pathologist misdiagnosing STS for histiocytic sarcoma.

A New Expression Model of Classical Electromagnetic Theory at the Micro Level

Because Maxwell's classical electromagnetic theory is a macro-electromagnetic theory based on the cognition of the 19th century and before the 19th century, and because the physics of the 20th century has gained new cognition in the microscopic field, considering that it is now the 21st century. Therefore, this article attempts to establish a set of micro-expression theory of Maxwell's macro-electromagnetism theory based on the new cognitions obtained at the micro-level since the 20th century, in order to promote the further development of Maxwell's classical electromagnetism theory in accordance with the cognition of the times.