Silver and gold nanoparticles as a novel approach to fight Sarcoptic mange in rabbits.

Various kinds of pets have been known to contract the ectoparasite Sarcoptes scabiei. Current acaricides are becoming less effective because of the resistance developed by the mite besides their adverse effects on the general activity and reproductive performance of domestic pets. For this reason, the present study aims to discover a novel and safe approach using silver and gold nanoparticles to fight Sarcoptic mange in rabbits as well as to explain their mechanism of action. 15 pet rabbits with clinical signs of Sarcoptic mange that were confirmed by the microscopic examination were used in our study. All rabbits used in this study were assessed positive for the presence of different developing stages of S. scabiei. Three groups of rabbits (n = 5) were used as follows: group (1) didn't receive any treatment, and group (2 and 3) was treated with either AgNPs or GNPs, respectively. Both nanoparticles were applied daily on the affected skin areas via a dressing and injected subcutaneously once a week for 2 weeks at a dose of 0.5 mg/kg bwt. Our results revealed that all rabbits were severely infested and took a mean score = 3. The skin lesions in rabbits that didn't receive any treatments progressed extensively and took a mean score = of 4. On the other hand, all nanoparticle-treated groups displayed marked improvement in the skin lesion and took an average score of 0-1. All NPs treated groups showed remarkable improvement in the microscopic pictures along with mild iNOS, TNF-α, and Cox-2 expression. Both nanoparticles could downregulate the m-RNA levels of IL-6 and IFγ and upregulate IL-10 and TGF-1ß genes to promote skin healing. Dressing rabbits with both NPs didn't affect either liver and kidney biomarkers or serum Ig levels indicating their safety. Our residual analysis detected AgNPs in the liver of rabbits but did not detect any residues of GNPs in such organs. We recommend using GNPs as an alternative acaricide to fight rabbit mange.

Digital Pathology for Better Clinical Practice.

(1) Background: Digital pathology (DP) is transforming the landscape of clinical practice, offering a revolutionary approach to traditional pathology analysis and diagnosis. (2) Methods: This innovative technology involves the digitization of traditional glass slides which enables pathologists to access, analyze, and share high-resolution whole-slide images (WSI) of tissue specimens in a digital format. By integrating cutting-edge imaging technology with advanced software, DP promises to enhance clinical practice in numerous ways. DP not only improves quality assurance and standardization but also allows remote collaboration among experts for a more accurate diagnosis. Artificial intelligence (AI) in pathology significantly improves cancer diagnosis, classification, and prognosis by automating various tasks. It also enhances the spatial analysis of tumor microenvironment (TME) and enables the discovery of new biomarkers, advancing their translation for therapeutic applications. (3) Results: The AI-driven immune assays, Immunoscore (IS) and Immunoscore-Immune Checkpoint (IS-IC), have emerged as powerful tools for improving cancer diagnosis, prognosis, and treatment selection by assessing the tumor immune contexture in cancer patients. Digital IS quantitative assessment performed on hematoxylin-eosin (H&E) and CD3+/CD8+ stained slides from colon cancer patients has proven to be more reproducible, concordant, and reliable than expert pathologists' evaluation of immune response. Outperforming traditional staging systems, IS demonstrated robust potential to enhance treatment efficiency in clinical practice, ultimately advancing cancer patient care. Certainly, addressing the challenges DP has encountered is essential to ensure its successful integration into clinical guidelines and its implementation into clinical use. (4) Conclusion: The ongoing progress in DP holds the potential to revolutionize pathology practices, emphasizing the need to incorporate powerful AI technologies, including IS, into clinical settings to enhance personalized cancer therapy.

Association of miR-146a-5p and miR-21-5p with Prognostic Features in Melanomas.

BACKGROUND: Cutaneous melanoma (CM) is one of the most lethal tumors among skin cancers and its incidence is rising worldwide. Recent data support the role of microRNAs (miRNAs) in melanoma carcinogenesis and their potential use as disease biomarkers. METHODS: We quantified the expression of miR-146a-5p and miR-21-5p in 170 formalin-fixed paraffin embedded (FFPE) samples of CM, namely 116 superficial spreading melanoma (SSM), 26 nodular melanoma (NM), and 28 lentigo maligna melanoma (LMM). We correlated miRNA expression with specific histopathologic features including Breslow thickness (BT), histological subtype, ulceration and regression status, and mitotic index. RESULTS: miR-146a-5p and miR-21-5p were significantly higher in NM compared to SSM and LMM. The positive correlation between miR-146a-5p and miR-21-5p expression and BT was confirmed for both miRNAs in SSM. Considering the ulceration status, we assessed that individual miR-21-5p expression was significantly higher in ulcerated CMs. The increased combined expression of the two miRNAs was strongly associated with ulceration (p = 0.0093) and higher mitotic rate (≥1/mm2) (p = 0.0005). We demonstrated that the combination of two-miRNA expression and prognostic features (BT and ulceration) can better differentiate cutaneous melanoma prognostic groups, considering overall survival and time-to-relapse clinical outcomes. Specifically, miRNA expression can further stratify prognostic groups among patients with BT ≥ 0.8 mm but without ulceration. Our findings provide further insights into the characterization of CM with specific prognostic features. The graphical abstract was created with BioRender.com.

Reproductive and endocrine-disrupting toxicity of pyrogallol in catfish (Clariasgariepinus).

Endocrine disruptors are synthetic or natural chemicals that can agonize/antagonize hormone receptors or can interfere with the production and secretion of hormones, leading to altered tissue histology and physiology. Pyrogallol is a contaminant widely distributed in aquatic environments that presents health risks to both humans and animals. However, the potential for endocrine disruption by pyrogallol, particularly in fish, are lacking. The purpose of this study was to shed light on how pyrogallol may affect hormone signalling, histopathology, and reproductive outcomes in African catfish Clarias gariepinus. To investigate this, African catfish were exposed to one sublethal concentration of pyrogallol at either 0, 1, 5 or 10 mg/L for 15 days. We then assessed the effects of pyrogallol on the thyroid gland as well as the reproductive system by measuring sex hormone, seminal quality, gonadal histopathology, and histochemistry. Thyroid stimulating hormone and thyroxine showed notable decreases in catfish, and triiodothyronine was decreased with 10 mg/L pyrogallol. Unlike luteinizing hormone, follicle-stimulating hormone was significantly reduced in fish following exposure to pyrogallol relative to controls. Testosterone was also decreased in fish following pyrogallol exposure, whereas 17ß-estradiol increased in catfish exposed to pyrogallol. Additionally, in response to pyrogallol toxicity, sperm quality indices, including count, spermatocrit, motility, and sperm viability were adversely affected in a concentration-dependent manner. Pyrogallol exposure also induced several changes in the gonad following exposure to 1, 5, or 10 mg/L. Deformed tubular structures, vacuolation, thickening of the basement membrane, hypertrophy of the seminiferous tubules, intense melanomacrophage localization, spermatozoa loss, and necrosis were all observed in the testes. In the ovary, atretic follicles, deteriorated mature oocytes, degenerated yolk globules, and an increase in perinucleolar oocytes were observed in catfish exposed to pyrogallol. These findings suggest that pyrogallol may act as endocrine disrupting substance in aquatic environments. Further research on the mechanisms by which pyrogallol impairs endocrine systems, particularly in fish, is recommended.

Correlation of Hysteroscopy With Histopathological Findings of the Endometrium in Women With Polycystic Ovary Syndrome (PCOS)-Related Infertility.

Introduction There have been numerous studies on the anovulatory factor, leading to infertility in women with polycystic ovary syndrome (PCOS); however, studies on the endometrium factor causing infertility in PCOS women are scarce. While hysteroscopy can accurately diagnose endometrial disorders such as endometrial polyps, it may be ineffective in detecting probable endometrial pathologies due to different hormonal habitats in these patients. Materials and methods Sixty patients with PCOS-related infertility were included in the study. All participants underwent hysteroscopic examination followed by endometrial biopsy and histopathological examination. The clinical and hormonal profiles of two main subgroups, that is, (a) normal endometrium (N), which included proliferative endometrium and secretory endometrium on histology, and (b) disordered endometrium (D), which included disordered endometrium on histology, were compared. Results There was no correlation between hysteroscopic and histopathological findings of PCOS infertile women. In the subgroup analysis of the two main histological types, that is, normal (proliferative and secretory) and disordered (disordered endometrium), age (28.70±4.66 vs. 32.9±5.61, p=0.012) and duration of amenorrhea (5.49±2.43 vs. 7.82±2.93, p=0.008) were significantly higher in the disordered group. There was a statistically nonsignificant higher BMI in the patients of the disordered endometrium group. Conclusion These findings suggest that endometrial biopsy and histopathological evaluation along with hysteroscopy should be desired in women with PCOS-related infertility, especially if they are in the late reproductive age group and have a longer duration of amenorrhea, regardless of endometrial thickening. This approach is essential to diagnose and treat endometrial disorder, which can be an additional cause of infertility, recurrent implantation failure, and recurrent pregnancy loss, in addition to ovulatory dysfunction.

Reproduction toxicity study with the synthetic amorphous silica SYLOID® AL-1 FP, HDK® N20, LUDOX® P T-40F and SYLOID® MX 107 in the earthworm species Eisenia fetida.

Ecotoxicology studies were performed in the earthworm Eisenia fetida with four different synthetic amorphous silica (SAS) (SYLOID® AL-1 FP, SYLOID® MX 107, LUDOX® P T-40F, and HDK® N20) mixed into artificial soil to determine a NOEC/LOEC for effects on reproduction (56 days after application), mortality and biomass development (28 days after application) using a standardized artificial soil with 10% peat. The LC50 for test-item effects on adult mortality, and an EC10 and EC50 for reproduction were also determined. Furthermore, earthworms underwent histopathology evaluation, and the amount of silica in different organs from these organisms was evaluated using EDX (Energy Dispersive X-ray Spectroscopy). Histopathology revealed no findings in any organ of the earthworms, except for desiccated dissepiments in evaluated decedents at extremely high SAS doses. To measure SAS uptake into the organs, a fully quantitative method for silica was established and validated using standards containing known concentrations of silica to ensure the accuracy of the analyses undertaken. Results from EDX analysis demonstrated the negligible presence of silicon within the brain ganglia and gonads of adult earthworms comparable to controls. Therefore, any deposition of the test items within these two organs was excluded. In contrast, traces of silicon higher than in controls were found in the intestinal lumina of the earthworms due to ingestion of SAS with soil and feed, but not in other organs.

Clinical, Morphological and Molecular Features of Spitz tumors.

Spitz tumors represent a heterogeneous group of challenging melanocytic neoplasms, displaying a range of biological behaviors, spanning from benign lesions, Spitz nevi (SN) to Spitz melanomas (SM), with intermediate lesions in between known as atypical Spitz tumors (AST). They are histologically characterized by large epithelioid and/or spindled melanocytes arranged in fascicles or nests, often associated with characteristic epidermal hyperplasia and fibrovascular stromal changes. In the last decade, the detection of mutually exclusive structural rearrangements involving receptor tyrosine kinases ROS1, ALK, NTRK1, NTRK2, NTRK3, RET, MET, serine threonine kinases BRAF and MAP3K8, or HRAS mutation, led to a clinical, morphological and molecular based classification of Spitz tumors. The recognition of some reproducible histological features can help dermatopathologist in assessing these lesions and can provide clues to predict the underlying molecular driver. In this review, we will focus on clinical and morphological findings in molecular Spitz tumor subgroups.

Histopathology of skin melanocytic lesions.

Melanocytic lesions are instable tumors, the genome of which and its changes determinate their morphology and biological properties. Intermediate lesions share histomorphological features of both, nevi and melanoma. Melanocytomas represent a group of them separated on the basis of recent molecular-biological studies. The article summarizes benign, intermediate, malignant and combined melanocytic skin lesions and offers practical recommendations for diagnosis.

Pathological Assessment of the Appendix in Appendectomies Performed in Children.

BACKGROUND: Acute appendicitis is known as the most common diagnosis of acute abdomen leading to surgery. Therefore, timely diagnosis is of special importance. This study was conducted with the aim of pathological assessment of the appendix in appendectomies performed in children to determine the rate of negative appendectomies and the predictors of negative appendectomy and to evaluate the paraclinical tools used in the diagnosis of acute appendicitis. METHODS: This is a cross-sectional descriptive study. All children who underwent appendectomy at Shahid Motahari Hospital in Urmia from March 2021 to March 2022 were examined. The required data including demographic, paraclinical, and final pathology characteristics were collected and recorded. The investigated cases were classified into positive and negative appendectomy categories for comparison. RESULTS: Among 234 pathology samples of the appendix, 22 cases were related to accidental appendectomy. In addition, 11.3% of cases were negative appendectomy and 88.7% were positive appendectomy. The age range of 8 to 14 years and male gender were associated with a lower negative appendectomy rate (both P<0.001). Inflammatory (49.5%) and gangrenous appendicitis (30.2%) were the most commonly reported histopathologies. Sonography had a sensitivity of 84%, a specificity of 79%, and an overall diagnostic accuracy of 83%. CONCLUSION: A relatively significant number of accidental and negative appendectomies are performed. More careful investigation and the use of expectant and medical treatment instead of surgery, especially in females and young children, can be effective in improving diagnostic accuracy and preventing negative appendectomies.

Non-gastrointestinal stromal tumor, mesenchymal neoplasms of the gastrointestinal tract: a review of tumor genetics, pathology, and cross-sectional imaging findings.

There is a diverse group of non-gastrointestinal stromal tumor (GIST), mesenchymal neoplasms of the gastrointestinal (GI) tract that demonstrate characteristic pathology and histogenesis as well as variable imaging findings and biological behavior. Recent advancements in tumor genetics have unveiled specific abnormalities associated with certain tumors, influencing their molecular pathogenesis, biology, response to treatment, and prognosis. Notably, giant fibrovascular polyps of the esophagus, identified through MDM2 gene amplifications, are now classified as liposarcomas. Some tumors exhibit distinctive patterns of disease distribution. Glomus tumors and plexiform fibromyxomas exhibit a pronounced affinity for the gastric antrum. In contrast, smooth muscle tumors within the GI tract are predominantly found in the esophagus and colorectum, surpassing the incidence of GISTs in these locations. Surgical resection suffices for symptomatic benign tumors; multimodality treatment may be necessary for frank sarcomas. This article aims to elucidate the cross-sectional imaging findings associated with a wide spectrum of these tumors, providing insights that align with their histopathological features.

Plasmodium falciparum alters the trophoblastic barrier and stroma villi organization of human placental villi explants.

BACKGROUND: The sequestration of Plasmodium falciparum infected erythrocytes in the placenta, and the resulting inflammatory response affects maternal and child health. Despite existing information, little is known about the direct impact of P. falciparum on the placental barrier formed by trophoblast and villous stroma. This study aimed to assess placental tissue damage caused by P. falciparum in human placental explants (HPEs). METHODS: HPEs from chorionic villi obtained of human term placentas (n = 9) from normal pregnancies were exposed to P. falciparum-infected erythrocytes (IE) for 24 h. HPEs were embedded in paraffin blocks and used to study tissue damage through histopathological and histochemical analysis and apoptosis using TUNEL staining. Culture supernatants were collected to measure cytokine and angiogenic factors and to determine LDH activity as a marker of cytotoxicity. A subset of archived human term placenta paraffin-embedded blocks from pregnant women with malaria were used to confirm ex vivo findings. RESULTS: Plasmodium falciparum-IE significantly damages the trophoblast layer and the villous stroma of the chorionic villi. The increased LDH activity and pathological findings such as syncytial knots, fibrin deposits, infarction, trophoblast detachment, and collagen disorganization supported these findings. The specific damage to the trophoblast and the thickening of the subjacent basal lamina were more pronounced in the ex vivo infection. In contrast, apoptosis was higher in the in vivo infection. This disparity could be attributed to the duration of exposure to the infection, which significantly varied between individuals naturally exposed over time and the 24-h exposure in the ex vivo HPE model. CONCLUSION: Exposure to P. falciparum-IE induces a detachment of the syncytiotrophoblast, disorganization of the stroma villi, and an increase in apoptosis, alterations that may be associated with adverse results such as intrauterine growth restriction and low birth weight.

Histopathological correlation of brain tumor recurrence vs. radiation effect post-radiosurgery as detected by MRI contrast clearance analysis: a validation study.

PURPOSE: The differentiation between adverse radiation effects (ARE) and tumor recurrence or progression (TRP) is a major decision-making point in the follow-up of patients with brain tumors. The advent of immunotherapy, targeted therapy and radiosurgery has made this distinction difficult to achieve in several clinical situations. Contrast clearance analysis (CCA) is a useful technique that can inform clinical decisions but has so far only been histologically validated in the context of high-grade gliomas. METHODS: This is a series of 7 patients, treated between 2018 and 2023, for various brain pathologies including brain metastasis, atypical meningioma, and high-grade glioma. MRI with contrast clearance analysis was used to inform clinical decisions and patients underwent surgical resection as indicated. The histopathology findings were compared with the CCA findings in all cases. RESULTS: All seven patients had been treated with gamma knife radiosurgery and were followed up with periodic MR imaging. All patients underwent CCA when the necessity to distinguish tumor recurrence from radiation necrosis arose, and subsequently underwent surgery as indicated. Concordance of CCA findings with histological findings was found in all cases (100%). CONCLUSIONS: Based on prior studies on GBM and the surgical findings in our series, delayed contrast extravasation MRI findings correlate well with histopathology across a wide spectrum of brain tumor pathologies. CCA can provide a quick diagnosis and have a direct impact on patients' treatment and outcomes.

Stroma AReactive Invasion Front Areas (SARIFA) predict poor survival in adenocarcinomas of the stomach and gastrooesophageal junction: a validation study.

Recently, the presence of "Stroma AReactive Invasion Front Areas" (SARIFA) has been described as a promising adverse prognostic factor in gastric cancer. However, the validity of this approach still needs to be tested. The aim of this study was to independently assess the utility of the proposed method in a well-characterised cohort of primary resected adenocarcinomas of stomach and gastrooesophageal junction (n = 392). SARIFA status was analysed on routine slides of resection specimens. Cases were divided into SARIFA-positive and negative groups and analysed in relation to clinicopathological and survival data. SARIFA positivity was found in 15.1% (n = 59) cases and was significantly associated with Lauren phenotype (p < 0.001), pT (p = 0.001), pN (p = 0.018), UICC stage (p = 0.031), tumour budding (p = 0.002), overall survival (p < 0.001) and cancer-specific survival (p < 0.001). SARIFA-positive tumours had a worse prognosis in the multivariate setting (HR = 1.847, 95% CI: 1.300-2.624, p = 0.001). SARIFA status is an independent prognostic factor in gastric cancer, in particular in locally advanced tumours.

Evaluation of Possible Toxic Effects of Boric Acid in Palourde Clam (Ruditapes decussatus) Through Histological Changes and Oxidative Responses.

The extensive utilization of boric acid, particularly in industrial and agricultural sectors, also engenders concerns regarding the toxicity of boron and its derivatives. Particularly, the behavior of boric acid at increasing concentrations in aquatic ecosystems remains poorly understood. In light of these concerns, this study aimed to investigate the toxicity of boric acid in bivalves, which occupy a critical position in the food chain. Specimens of Ruditapes decussatus, which had not been previously exposed to any pollutants and were cultivated under controlled conditions, were subjected to three different concentrations of boric acid (0.05 mg/L, 0.5 mg/L, and 5 mg/L) in vitro for 96 h. Following the exposure period, the specimens were assessed for histological changes (the mantle, gill, and digestive gland) and specific oxidative parameters (the gill and digestive gland), including superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase, and lipid peroxidation (LPO). The research findings indicated that boric acid primarily induced oxidative damage at the applied concentrations and increased antioxidant levels (p < 0.05). Moreover, although no significant histopathological abnormalities were observed in the examined histological sections, subtle changes were noted. This study evaluated the potential adverse effects of boric acid on bivalves, which are crucial components of the aquatic food chain, utilizing histological and specific physiological parameters following its introduction into aquatic environments. It is anticipated that the findings of this study will contribute to the development of new insights and perspectives regarding the extensive use of boric acid.

Histopathological Analysis of Brains from Dogs Infected with Canine Distemper Virus.

We describe the use of conventional histology and immunohistochemistry against canine distemper virus (CDV) to examine the brains of domestic dogs with a confirmed diagnosis of CDV infection. Histologically, to identify the main typical lesions, we used conventional H&E stain; to evaluate the progressive demyelination, we used Luxol Fast Blue stain; and to identify the presence of viral particles in these affected regions, we used immunohistochemistry against CDV. We confirm that the histopathological analysis of brains of distemper-infected dogs is a powerful tool to evaluate the typical brain lesions and could be used as an interesting natural model to continue studying the pathogenesis of canine distemper in different species and/or other morbillivirus infections, like measles.

Mistakes in utilising histopathology for the management of liver disease.

INTRODUCTION: Liver biopsy has become selective due to its invasiveness, potential adverse effects, patient acceptance and cost. Furthermore, the emergence of noninvasive tests (NITs) has challenged the necessity of liver biopsies in specific clinical situations. However, liver biopsy continues to play a crucial role in disease diagnosis, prognosis, and evaluating treatment compliance and response in selected patients. AREAS COVERED: In this narrative review, we discuss the errors and the shortcomings that can occur at various stages, from the initial patient selection for a liver biopsy to the final reporting phase, and strategies to address them. Clinicians and pathologists must take all necessary precautions to mitigate potential shortcomings that could compromise the value of liver biopsies. EXPERT OPINION: The increasing sophistication of NITs offers a safer, more convenient, and potentially more cost-effective approach to diagnosing chronic liver disease, especially for assessing the degree of liver fibrosis. As NITs continue to evolve, liver biopsy will likely transition to a more targeted role, ensuring optimal patient care in the ever-changing field of hepatology. However, liver biopsy will continue to have a pivotal role in assessing acute liver disease where the diagnostic yield of the liver biopsy still outweighs that of NITs.

Diagnostic Value of Combined-Diagnostic Methods of Brain Tuberculoma Tissue Specimens: A Case Series.

Background: The diagnosis of brain tuberculoma (BT) is sometimes challenging. Herein, we presented a case series to evaluate the combined-diagnostic methods, including acid-fast bacilli (AFB) stain, polymerase chain reaction (PCR), Gene Xpert, and histopathology, of tuberculoma tissue specimens (TTSs). Patients and Methods: A total of 16 patients (11 human immunodeficiency virus [HIV]-positive, 5 HIV-negative) with BT confirmed by combined-diagnostic methods of TTS were included in this study. Clinical data, including clinical symptoms, laboratory tests, neuroimaging features, histopathology, treatment, and prognosis, were assessed in all patients. Results: There were 10 male and 6 female patients (range, 18-73 years). Acid-fast bacilli stain and PCR of TTSs were positive in 11 and 10 patients, respectively. The sensitivity of Gene Xpert of TTSs was (80.0%; 8/10). Nine (56.3%; 9/16) patients were diagnosed with BT by histopathology. After receiving antituberculosis treatment, 12 (75.0%; 12/16) patients improved clinically to a considerable extent. Conclusions: The combined-diagnostic methods of TTS may improve the diagnostic efficiency of BT.

Electrocautery-Assisted Management of Unilateral Pyogenic Granuloma: A Case Report.

Pyogenic granuloma (PG) refers to an acquired benign proliferation most commonly seen within the oral cavity involving lips, palate, and gingiva. The term is misleading since it is a type of lobular capillary haemangioma but not an infection. It frequently recurs but lacks the capacity for malignant alteration. Depending on where the PG is located, one may experience discomfort or irritation. PGs often lead to differential diagnoses by clinicians, which include capillary hemangioma, neurofibroma, melanoma, and hyperplasia. Therefore, one must confirm a PG by diagnosing and analysing it by clinical and histopathological examinations, and treatment options should be formulated according to the evaluation. Sometimes, a biopsy of the lesion can be taken for final diagnosis. Various treatment approaches are available, including conventional scalpel excision, laser, electrocautery, and cryotherapy. Surgical excision is preferable due to the likelihood of malignancy, as it provides the best cosmetic appearance and produces a specimen for pathologic assessment. After confirming all the clinical evaluatory parameters and routine haematological examinations, which proved satisfactory and within normal ranges, this case of a 45-year-old female with soft tissue growth of the gingival origin was managed by electrocautery, and the PG was confirmed by a clinical-histopathological examination.