NETosis in Parasitic Infections: A Puzzle That Remains Unsolved.

Neutrophils are the key players in the innate immune system, being weaponized with numerous strategies to eliminate pathogens. The production of extracellular traps is one of the effector mechanisms operated by neutrophils in a process called NETosis. Neutrophil extracellular traps (NETs) are complex webs of extracellular DNA studded with histones and cytoplasmic granular proteins. Since their first description in 2004, NETs have been widely investigated in different infectious processes. Bacteria, viruses, and fungi have been shown to induce the generation of NETs. Knowledge is only beginning to emerge about the participation of DNA webs in the host's battle against parasitic infections. Referring to helminthic infections, we ought to look beyond the scope of confining the roles of NETs solely to parasitic ensnarement or immobilization. Hence, this review provides detailed insights into the less-explored activities of NETs against invading helminths. In addition, most of the studies that have addressed the implications of NETs in protozoan infections have chiefly focused on their protective side, either through trapping or killing. Challenging this belief, we propose several limitations regarding protozoan-NETs interaction. One of many is the duality in the functional responses of NETs, in which both the positive and pathological aspects seem to be closely intertwined.

Nitric oxide in parasitic infections: a friend or foe?

The complex interaction between the host and the parasite remains a puzzling question. Control of parasitic infections requires an efficient immune response that must be balanced against destructive pathological consequences. Nitric oxide is a nitrogenous free radical which has many molecular targets and serves diverse functions. Apart from being a signaling messenger, nitric oxide is critical for controlling numerous infections. There is still controversy surrounding the exact role of nitric oxide in the immune response against different parasitic species. It proved protective against intracellular protozoa, as well as extracellular helminths. At the same time, it plays a pivotal role in stimulating detrimental pathological changes in the infected hosts. Several reports have discussed the anti-parasitic and immunoregulatory functions of nitric oxide, which could directly influence the control of the infection. Nevertheless, there is scarce literature addressing the harmful cytotoxic impacts of this mediator. Thus, this review provides insights into the most updated concepts and controversies regarding the dual nature and opposing sides of nitric oxide during the course of different parasitic infections.

The Clinical and Pathologic Features of Intracholecystic Papillary-Tubular Neoplasms of the Gallbladder.

Intracholecystic papillary-tubular neoplasm denotes a discrete mucosal-based neoplastic proliferation into the gallbladder lumen. It is diagnosed incidentally during cholecystectomy or radiologically during a workup for abdominal pain. The majority of polypoid lesions in the gallbladder are non-neoplastic; therefore, pathologic examination is the gold standard to establish this diagnosis. Intracholecystic papillary-tubular neoplasm is considered as premalignant, although associated invasive carcinomas may be present in the specimen. Invasive carcinoma arising from intracholecystic papillary-tubular neoplasm have a better prognosis than de novo gallbladder carcinomas. The pathology of intracholecystic papillary-tubular neoplasm, including the challenges involved in the diagnosis of this entity, is discussed.

Current status of intestinal parasitosis among patients attending teaching hospitals in Zagazig district, Northeastern Egypt.

Almost 80% of health problems in the developing world are due to malnutrition and infectious diseases, which are mainly parasitic. Updated records on the prevalence of parasitic infections and the potential risk factors are essential to enhancing control strategies. Therefore, this study was conducted to evaluate the current situation of intestinal parasitism among patients attending teaching hospitals in Zagazig district, Northeastern Egypt. The study involved five hundred cases. They were all subjected to faecal examination using direct smear measure and two commercial faecal concentrators: Mini-Parasep® solvent-free and Mini-FLOTAC procedures. Mini-FLOTAC was performed with two solutions (FS2: saturated sodium chloride and FS7: zinc sulphate). The overall prevalence of intestinal parasitic infections was 56%. Different species were identified, like Giardia lamblia (12.6%), Entamoeba histolytica/dispar (10%), Ascaris lumbricoides (8.8%) and Hymenolepis nana (8.6%). Data analyses revealed a significant association of intestinal parasitism with different socio-demographic features of the participants. Our results showed a better diagnostic performance of Mini-Parasep® in the overall recovery of intestinal parasites. It was more accurate than Mini-FLOTAC in diagnosing both helminths and protozoan infections. Mini-FLOTAC (FS2) exhibited a higher sensitivity than FS7 for helminth recovery (74.6% vs 53.4%), while FS7 was more sensitive for protozoan infections (50.6% vs 43.8%). Intestinal parasitosis remains a challenging health problem in Zagazig city, wherever reliable diagnostic approaches are limited. Thus, our study has proposed the value of the commercial concentrators (Mini-Parasep® and Mini-FLOTAC) as alternative techniques for diagnosing a large variety of parasite species in resource-constrained settings.

Real-time colorectal cancer diagnosis using PR-OCT with deep learning.

Prior reports have shown optical coherence tomography (OCT) can differentiate normal colonic mucosa from neoplasia, potentially offering an alternative technique to endoscopic biopsy - the current gold-standard colorectal cancer screening and surveillance modality. To help clinical translation limited by processing the large volume of generated data, we designed a deep learning-based pattern recognition (PR) OCT system that automates image processing and provides accurate diagnosis potentially in real-time. Method: OCT is an emerging imaging technique to obtain 3-dimensional (3D) "optical biopsies" of biological samples with high resolution. We designed a convolutional neural network to capture the structure patterns in human colon OCT images. The network is trained and tested using around 26,000 OCT images acquired from 20 tumor areas, 16 benign areas, and 6 other abnormal areas. Results: The trained network successfully detected patterns that identify normal and neoplastic colorectal tissue. Experimental diagnoses predicted by the PR-OCT system were compared to the known histologic findings and quantitatively evaluated. A sensitivity of 100% and specificity of 99.7% can be reached. Further, the area under the receiver operating characteristic (ROC) curves (AUC) of 0.998 is achieved. Conclusions: Our results demonstrate that PR-OCT can be used to give an accurate real-time computer-aided diagnosis of colonic neoplastic mucosa. Future development of this system as an "optical biopsy" tool to assist doctors in real-time for early mucosal neoplasms screening and treatment evaluation following initial oncologic therapy is planned.

Clinical Decision Support for Ovarian Carcinoma Subtype Classification: A Pilot Observer Study With Pathology Trainees.

CONTEXT.­: Clinical decision support (CDS) systems could assist less experienced pathologists with certain diagnostic tasks for which subspecialty training or extensive experience is typically needed. The effect of decision support on pathologist performance for such diagnostic tasks has not been examined. OBJECTIVE.­: To examine the impact of a CDS tool for the classification of ovarian carcinoma subtypes by pathology trainees in a pilot observer study using digital pathology. DESIGN.­: Histologic review on 90 whole slide images from 75 ovarian cancer patients was conducted by 6 pathology residents using: (1) unaided review of whole slide images, and (2) aided review, where in addition to whole slide images observers used a CDS tool that provided information about the presence of 8 histologic features important for subtype classification that were identified previously by an expert in gynecologic pathology. The reference standard of ovarian subtype consisted of majority consensus from a panel of 3 gynecologic pathology experts. RESULTS.­: Aided review improved pairwise concordance with the reference standard for 5 of 6 observers by 3.3% to 17.8% (for 2 observers, increase was statistically significant) and mean interobserver agreement by 9.2% (not statistically significant). Observers benefited the most when the CDS tool prompted them to look for missed histologic features that were definitive for a certain subtype. Observer performance varied widely across cases with unanimous and nonunanimous reference classification, supporting the need for balancing data sets in terms of case difficulty. CONCLUSIONS.­: Findings showed the potential of CDS systems to close the knowledge gap between pathologists for complex diagnostic tasks.

Co-registered photoacoustic and ultrasound imaging of human colorectal cancer.

Colorectal cancer is the second most common malignancy diagnosed globally. Critical gaps exist in diagnostic and surveillance imaging modalities for colorectal neoplasia. Although prior studies have demonstrated the capability of photoacoustic imaging techniques to differentiate normal from neoplastic tissue in the gastrointestinal tract, evaluation of deep tissue with a fast speed and a large field of view remains limited. To investigate the ability of photoacoustic technology to image deeper tissue, we conducted a pilot study using a real-time co-registered photoacoustic tomography (PAT) and ultrasound (US) system. A total of 23 ex vivo human colorectal tissue samples were imaged immediately after surgical resection. Co-registered photoacoustic images of malignancies showed significantly increased PAT signal compared to normal regions of the same sample. The quantitative relative total hemoglobin (rHbT) concentration computed from four optical wavelengths, the spectral features, such as the mean spectral slope, and 0.5-MHz intercept extracted from PAT and US spectral data, and image features, such as the first- and second-order statistics along with the standard deviation of the mean radon transform of PAT images, have shown statistical significance between untreated colorectal tumors and the normal tissue. Using either a logistic regression model or a support vector machine, the best set of parameters of rHbT and PAT intercept has achieved area-under-the-curve (AUC) values of 0.97 and 0.95 for both training and testing data sets, respectively, for prediction of histologically confirmed invasive carcinoma.