Cytopathology Research Articles

Diagnosis and treatment of Anaplasma centrale in a domestic cat at Animal Hospital of Hasanuddin University Makassar

Anaplasmosis is a disease caused by obligate gram-negative intracellular bacteria. Anaplasma in cats is generally infected by Anaplasma phagocytophilum, however there are very limited reports of Anaplasma bovis such as Anaplasma marginale and Anaplasma centrale being reported to infect cats. This is the first report of anaplasmosis caused by Anaplasma centrale in cats. The owner brought a one-year-old female domestic cat to the Animal Hospital of Hasanuddin University in Makassar with the condition of not wanting to eat, weak, lethargic, dehydrated, and not defaecating. Diagnosis is carried out through anamnesis, physical examination, clinical examination, and laboratory examination, in the form of haematology and blood smear tests. The results of the examination revealed flea infestation, a blood test identified Anaplasma centrale with characteristics such as the presence of morulae in the middle part of the erythrocytes, and routine blood work showed anaemia which was seen in the MCV parameters increasing and the MCHC values decreased. Treatment consists of administration of antibiotics, anti-inflammatory drugs, and supportive therapy. The cat showed good results, with symptoms starting to disappear and the animal appeared active.

Allergy as a potential aetiology of micturition disorders in children

Introduction: In the paediatric population, the co-occurrence of micturition disorders with allergic diseases is often observed. The aim of this study was to demonstrate whether allergic aetiology may be a potential cause of micturition disorders in children. Materials and methods: The study included 69 children who were divided into two main cohorts: patients with and without voiding disorders. Among them, subgroups of children with allergies and children without allergic reactions were distinguished. In all patients, the absolute and percentage content of eosinophils in the blood and selected immune parameters were assessed. The usefulness of minimally invasive diagnostic methods in the diagnosis of allergic aetiology of micturition disorders in children was also evaluated. Results: It was shown that in the cohort of patients with voiding disorders, monosymptomatic nocturnal enuresis occurred statistically more commonly in the group of children with atopy compared to the children without atopy. There were no statistically significant differences between the groups in terms of the percentage values of immune parameters. It was found that urine cytology and urethral swab were not helpful tools in assessing allergic reactions in the bladder. Conclusions: The results of the study indicate that monosymptomatic nocturnal enuresis co-occurs with allergy significantly more often than with other types of voiding disorders. The importance of urine cytology and urethral smear for the presence of eosinophils in demonstrating the allergic aetiology of micturition disorders in children was not confirmed.

DPD-Net: Dual-path Proposal Discriminative Network for abnormal cell detection in cervical cytology images

Cytology inspection is a basic examination for the prevention of cervical cancer, which is still done manually and is a labor-intensive and time-consuming process with high inter-observer variability. With the rapid development of deep learning, automatic cytology inspection methods have achieved gratifying results, but the research on the effective detection of abnormal cells remains insufficient. In this paper, we propose a novel Dual-path Proposal Discriminative detection Network (DPD-Net) for abnormal cell detection in cervical cytology images. Specifically, considering the distinctive characteristics of abnormal nuclei such as increased sizes and unclear boundaries, we first design a dual-path architecture, where the cell path acts as the primary detector and the nucleus path serves as the auxiliary detector to provide supplementary information. In addition, the proposal information isolation may result in ambiguous classification boundaries. To transcend individual features and delve deeper into cellular relationships as implicit features, the proposal relation modules are added to explore relation information and refine features adaptively. Finally, to tackle problems of intra-class variation and inter-class similarity, we calculate the proposal contrastive losses in two paths respectively to guide a better distinction between the features of normal and abnormal cells. The proposed method is evaluated on our in-house cervical liquid-based cytology dataset (CLBC) and a public pap smear cytology dataset (CRIC) and gains satisfactory results, outperforming other state-of-the-art methods. Comprehensive experiments demonstrate the superiority of the proposed DPD-Net and the effectiveness of each proposed component. Our code is available at https://github.com/chaisiyii/DPD-Net.

Вплив вживання психоактивних речовин та інфекцій, що передаються статевим шляхом, на цитологічний стан шийки матки

The introduction addresses the societal stigma surrounding psychoactive substance abuse and its implications for women’s health, particularly concerning cervical health. It sets the context for the study by highlighting the need to understand the impact of substance abuse and sexually transmitted infections (STIs) on cervical health. Purpose - to investigate the effects of psychoactive substance abuse and concurrent STIs on the health of the cervix in women. The study seeks to identify correlations between substance abuse, STIs, and cervical pathologies, providing valuable insights for healthcare strategies. Materials and methods. The study involved a sample of 160 women divided into groups based on their use of psychoactive substances and the presence of STIs. Cervical cytological smears were collected and analysed using Romanowsky-Giemsa and Papanicolaou staining methods. This approach aimed to detect and categorize any cellular abnormalities in the cervical epithelium. Results. The findings revealed a significant correlation between the abuse of psychoactive substances and the frequency of squamous cell abnormalities in the cervix, especially in those with concurrent STIs. Conditions like koilocytosis and low-grade squamous intraepithelial lesions (LSIL) were notably prevalent among substance abusers, indicating an increased risk for cervical dysplasia and potential progression to cervical cancer. Conclusions. The study concludes that psychoactive substance abuse, particularly in combination with STIs, significantly increases the risk of cervical pathologies in women. This underscores the necessity for enhanced cervical cancer screening and prevention strategies targeted at women who abuse psychoactive substances. The findings highlight the importance of addressing substance abuse and STIs in women’s health programs and public health initiatives, especially in high-risk groups. The study protocol was approved by the Local ethics committees of the institutions mentioned in the paper. An informed parental consent was obtained for the study in women. No conflict of interests was declared by the authors.

Autoimmune hemolytic anemia in a preoperative patient: a case report and literature review

Background: In patients undergoing elective surgery, it is known that as many as one-third have preoperative anemia. Preoperative anemia is associated with an almost five-fold increase in the likelihood of postoperative mortality. So, it is essential to know the cause of anemia so that the management is appropriate so that surgery can be performed safely and prevent patients from dying on the operating table or postoperatively. This case report aims to describe the pathogenesis of the laboratory findings in a patient with autoimmune hemolytic anemia (AIHA) who was accidentally diagnosed during preoperative screening and the management performed. Case: A 65-year-old man with an enlarged prostate was scheduled for elective surgery. Preoperative examination revealed anemic right and left conjunctiva, decreased erythrocytes, hemoglobin, hematocrit, and increased MCV, MCH, and MCHC, peripheral blood smear dominated by red cell agglutination and positive direct Coomb's test. The patient was given methylprednisolone 62.5 mg intravenously before transfusion and given a transfusion of 2 units of slow drip packed red cells (PRC) under close supervision. There were no transfusion reactions during and after transfusion. There was an increase in Hb after transfusion so that the patient could be operated on. Conclusion: The patient in this case was diagnosed with AIHA based on preoperative laboratory findings. Laboratory results showed evidence of autoimmune hemolytic anemia with decreased erythrocytes, hemoglobin, hematocrits, spherocytes, and agglutination on peripheral blood smear and positive Coomb's test. Rapid identification and treatment of anemia help improve preoperative conditions.

Metagenomic next-generation sequencing for detecting Aspergillosis pneumonia in immunocompromised patients: a retrospective study.

The identification of Aspergillus by metagenomic next-generation sequencing (mNGS) remains a challenging task due to the difficulty of nucleic acid extraction. The objective of this study was to determine whether mNGS could provide an accurate and efficient method for detecting invasive pulmonary aspergillosis (IPA) in immunocompromised patients (ICP). A total of 133 ICP admitted to the ICU between January 2020 and September 2022 were enrolled in the study, of which 46 were diagnosed with IPA and 87 were non-IPA cases. The bronchoalveolar lavage fluid (BALF) was analyzed for the presence of Aspergillosis and other co-pathogens using mNGS, and its diagnostic performance was compared to conventional microbial tests (CMTs) that included smear, cultures, serum and BALF galactomannan (GM) test. Clinical composite diagnosis was used as the reference standard. mNGS had a sensitivity, specificity, and accuracy of 82.6%, 97.7%, and 92.5%, respectively, in diagnosing IPA. These findings were comparable to those of the combination of multiple CMTs. Interestingly, the sensitivity of mNGS was superior to that of any single CMT method, as demonstrated by comparisons with smears (8.7%, P < 0.001), culture (39.1%, P < 0.001), serum GM (23.9%, P < 0.001) and BALF GM (69.6%, P = 0.031). mNGS was capable of accurately distinguish strains of Aspergillus genus, with a consistency of 77.8% with culture. Furthermore, mNGS also identified A. fumigatus, A. flavus, A. terrestris, A. oryzae and Mucor spp. in culture-negative cases. The sequencing reads of Aspergillus by mNGS exhibited extensive variation, ranging from 11 to1702. A positive correlation was observed between the optical density index of BALF GM and unique reads by mNGS (r = 0.607, P = 0.001) in BALF-GM positive patients. Notably, mNGS was able to diagnose 35 out of 37 cases with mixed infection, with P. jirovecii and cytomegalovirus being the most common co-pathogens. mNGS presents a feasible and remarkably sensitive approach for detecting Aspergillus in ICP, thereby serving as a valuable adjunctive tool to CMT. Furthermore, mNGS's ability to accurately identify fungal species and co-pathogens can assist in guiding appropriate antimicrobial therapy.

Immunocytochemistry on frozen-embedded cell block for the diagnosis of hematolymphoid cytology specimen: a straightforward alternative to the conventional cell block.

Agarose-based cell block (CB) technique can be modified to be combined with the frozen section technique for the preparation of a high-quality frozen-embedded CB (F-CB) from an effusion or fine-needle aspiration (FNA) cytology sample. This combined technique can be effectively used for the immunocharacterization of the hematolymphoid cells on F-CB. To demonstrate the applicability of performing diagnostic ICC on F-CB, we have analyzed the immunophenotype of the hematolymphoid cells in a series of eight cases of effusions and eight cases of FNA cytology specimens by using CB-ICC on sections cut from frozen-embedded CBs. The SurePathTM residue or cytologic material scraped off from the FNA cytology smear that was diagnostic for or suspicious of hematolymphoid malignancy was pelleted and pre-embedded in agarose. Half of the agarose-embedded pellet was frozen-embedded in OCT compound for the preparation of F-CB, while the other half was processed for the preparation of paraffin-embedded CB. Sections cut from the F-CB and P-CB were used for CB-ICC. Panels of ICC on the F-CBs could enable the immunocytochemical differential diagnosis of large cell hematologic malignancies that encompass anaplastic large cell lymphoma and other forms of large-cell hematolymphoid malignancies such as large B-cell lymphomas, anaplastic plasma cell myeloma, myeloid sarcoma, and T-lymphoblastic lymphoma. It also appeared that the small B-cell lymphomas in the effusions or FNAs could be differentially diagnosed with the aid of CB-ICC on the F-CB. A modified agarose-based CB technique can be combined with the frozen-embedded CB method for the preparation of F-CB that can be directly used for the immunocytochemical differential diagnosis of hematolymphoid cytology samples.

Cytomorphological study of pap smear and its efficacy to detect various cervical lesions

: Cervical lesions require screening for early diagnosis to differentiate between non-neoplastic and neoplastic lesions of cervix. The present research aimed to evaluate the prevalence of various cervical lesions and detect the efficacy as a screening test of pap smear for early diagnosis of cervical lesions. : The current retrospective study was conducted in the Department of Pathology, SSMC, Rewa, M.P. Total 658 cervical pap smears were retrieved, re-examined and re-classified according to the revised Bethesda system for reporting of cervical cytology, 2014. Out of 658 pap smears, 234 biopsies were available, which were re-examined histopathologically and correlation was done with their corresponding cytological findings.: Out of 658 pap smears, negative for intraepithelial lesion or malignancy (NILM) was found in 74.47% smears, while the prevalence of epithelial cell abnormalities (ECA) was 24.32%. Amongst ECA, most common (11.86%) cervical lesion was low-grade squamous intraepithelial lesion (LSIL). Diagnostic sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for the diagnosis of pre-invasive and invasive cervical lesions was found 70.54%, 81.9%, 82.72%, 69.35% and 75.6% respectively.: The current study showed that pap smear cytology is able to detect various cervical lesions with a diagnostic accuracy of 75.6%. So, women belonging to reproductive or postmenopausal age-group should be routinely screened for cervical lesions by non-invasive pap smear method. Conclusively, early diagnosis of cervical lesions is possible, thus reducing the incidence of invasive cervical carcinoma.

Correlation of intraoperative squash smear and histopathology in central nervous system lesions: A 6-year retrospective study in a tertiary care hospital in Kerala

Intraoperative squash smear cytology is considered to be of great value in intraoperative consultation of CNS pathology. It is a simple and reliable tool for rapid intraoperative diagnosis of CNS tumors. The study was undertaken to assess the accuracy of intraoperative squash smear in the diagnosis of CNS lesions and to correlate the squash cytology diagnosis with histopathological diagnosis taking the latter as the gold standard. A retrospective study of 38 cases of CNS lesions from which samples were collected by surgery or biopsy for intraoperative consultations and histopathological diagnosis. Radiologically confirmed cases were only included in the study. Smears were prepared from the biopsy sample obtained at the time of operation and were stained with hematoxylin and eosin. Remaining tissue submitted for histopathology was later correlated with intraoperative cytology diagnosis. Out of 38 cases, histopathological diagnosis was compatible with cytological diagnosis in 36 cases, two cases showed discrepancies. The diagnostic accuracy of squash cytology was 94.73%. Even though two cases were diagnosed differently in cytology, it was proved to be a malignant tumor both in squash cytology and histopathological diagnosis. Hence sensitivity, specificity, positive predictive value and negative predictive value in detecting the neoplastic condition on cytology was 100% respectively. Squash smear is a rapid, self-sufficient and cost effective method for the intraoperative diagnosis of CNS tumors. It can be considered as a mirror image to histopathological diagnosis and is of great value in intraoperative consultation of CNS pathology.

Dipping contacts - a novel type of contact site at the interface between membraneless organelles and membranes.

Liquid-liquid phase separation is a major mechanism for organizing macromolecules, particularly proteins with intrinsically disordered regions, in compartments not limited by a membrane or a scaffold. The cell can therefore be perceived as a complex emulsion containing many of these membraneless organelles, also referred to as biomolecular condensates, together with numerous membrane-bound organelles. It is currently unclear how such a complex concoction operates to allow for intracellular trafficking, signaling and metabolic processes to occur with high spatiotemporal precision. Based on experimental observations of synaptic vesicle condensates - a membraneless organelle that is in fact packed with membranes - we present here the framework of dipping contacts: a novel type of contact site between membraneless organelles and membranes. In this Hypothesis, we propose that our framework of dipping contacts can serve as a foundation to investigate the interface that couples the diffusion and material properties of condensates to biochemical processes occurring in membranes. The identity and regulation of this interface is especially critical in the case of neurodegenerative diseases, where aberrant inclusions of misfolded proteins and damaged organelles underlie cellular pathology.

The urgency of Burkitt lymphoma diagnosis in fluid cytology-A tertiary care experience.

Burkitt lymphoma (BL) is an aggressive high-grade B-cell non-Hodgkin lymphoma commonly diagnosed in young age and is known to involve extra nodal sites. But the involvement of body fluids by BL is an uncommon presentation. Rapid diagnosis of BL is vital to prevent complications like tumour lysis syndrome. Cytological examination of body fluids continues to be an indispensable tool for rapid diagnosis of BL. In this study, we aim to study the clinical, cytomorphological and immunophenotypic characteristics of BL involving serous effusions and other fluids. In this retrospective study, 17 cases reported as BL in fluid cytology from 2016 to 2022 were collected and reviewed. We performed a comprehensive analysis of the clinical data, cytomorphological features, immunophenotyping data along with the haematological workup of these cases. We have also compared with the histopathological diagnosis for those cases where biopsy was available. BL more commonly involved ascitic fluid (52%), followed by pleural fluid (4 cases) and cerebrospinal fluid (CSF; 4 cases). Primary diagnosis of BL in fluid was done in 88% of the cases. Bone marrow involvement was noted in two cases. Cytological smears showed discrete monomorphous population of medium-sized atypical lymphoid cells with frequent apoptotic bodies. Classic cytoplasmic punched out vacuoles were observed in 88% of the cases. Immunophenotyping data was available for 12 cases in which tumour cells showed positivity for CD20 (100%), CD10 (4 of 7 cases), BCL6 (3 of 5 cases) and cMYC (7 of 7 cases-100%) and were negative for Terminal deoxynucleotidyl transferase (TdT) (11 of 11 cases). Mean Ki67 labelling index was 95%. Histopathological diagnosis was available for 9 cases, and there was 100% agreement between cytological and histopathological diagnosis in 7 cases. Precise diagnosis of BL can be rendered in body fluids by identification of classic cytomorphological features and by performing supportive ancillary tests in fluids for immunophenotyping.

WATS 3D : An Interobserver Study of Barrett's Esophagus-Associated Dysplasia Among Gastrointestinal Pathologists.

Wide-area transepithelial sampling with 3-dimensional computer-assisted analysis (WATS 3D ) has been shown to increase the detection rate of dysplasia (and intestinal metaplasia) in patients with Barrett's esophagus (BE). The purpose of this study was to evaluate the interobserver variability and accuracy of diagnosing BE-associated dysplasia in WATS 3D specimens among gastrointestinal (GI) pathologists without prior experience with this technology. Five GI pathologists underwent a 4-hour in-person (at microscope) and virtual training session and then evaluated digital images of discrete cellular foci from 60 WATS 3D cases with BE (20 nondysplastic BE [NDBE], 20 low-grade dysplasia [LGD], and 20 high-grade dysplasia/esophageal adenocarcinoma [HGD/EAC]). Each case consisted of 1 hematoxylin and eosin-stained image (cell block), and 1 liquid cytology or papanicolaou-stained smear image (120 images in total). The overall kappa value among the 5 study pathologists was excellent (overall kappa = 0.93; kappa = 0.93 and 0.97 for cell block and smear specimens, respectively). There were no significant differences noted in kappa values in interpretation of the cell block vs smear specimens or in any of the individual diagnostic categories when the latter were evaluated separately. Furthermore, agreement was perfect (100%) regarding detection of neoplasia (either LGD, HGD, or EAC). Diagnoses were made with complete confidence in 91% of instances. We conclude that GI pathologists, without any prior experience in interpretation of WATS 3D specimens, can undergo a short training session and then diagnose these specimens with a very high level of accuracy and reproducibility.

The use of urine lipoarabinomannan for establishing pulmonary TB in HIV patient: case report and systematic review

Introduction: Indonesia is still the country that provides the second-largest estimated number of TB cases worldwide. Several patients had TB with HIV-positive. HIV-positive patients with symptoms suggestive of pulmonary tuberculosis often difficult to produce sputum of sufficient quality. Lateral flow lipoarabinomannan examination with urine specimens is expected to be easy, inexpensive, fast, and accurate point-of-care testing. The aim of this research was to assess the sensitivity and specificity of the lateral flow method in detecting lipoarabinomannan (LAM) from urine specimens in HIV-positive patients with suspected pulmonary tuberculosis. Sputum cultures were utilised as a reference standard. Case Description: A 21-year-old male patient came to the clinic complaining of a cough that had not subsided since the previous month. Cough felt throughout the day with a little white phlegm. The patient admitted to having high-risk sexual behavior and had been tested positive for HIV but had not started antiretroviral therapy. The laboratory examination results showed that the leukocyte count was 3600/mm3 and the radiological examination revealed a chest X-ray within normal limits. The patient had been tested for sputum smears with negative results but was still advised to start TB treatment. The patient has not started treatment because he feels that his sputum smear test results are negative. Currently, the patient is not willing to have his sputum checked again. The polyclinic doctor knows the lipoarabinomannan (LAM) examination that uses urine specimens to diagnose TB but does not yet know its effectiveness for this patient. Conclusion: In this case report, the patient was unwilling to do a diagnostic test related to the TB. The systematic review was that the Alere Determine™ TB LAM Ag may not be clinically applicable for diagnosing tuberculosis infection in patients living with HIV at this time. However, Fujifilm SILVAMP TB LAM® could be regarded as a supplementary tool to the established diagnostic protocol for tuberculosis in HIV-positive patients.

Conventional PAP Smear or Liquid-Based Cytology, The Better Screening Tool for Cervical Cancer: a Comparative Study at a Tertiary Care Center in North-East India

Conventional PAP Smear or Liquid-Based Cytology, The Better Screening Tool for Cervical Cancer: a Comparative Study at a Tertiary Care Center in North-East India

Self-supervised learning-based cervical cytology for the triage of HPV-positive women in resource-limited settings and low-data regime

Screening Papanicolaou test samples has proven to be highly effective in reducing cervical cancer-related mortality. However, the lack of trained cytopathologists hinders its widespread implementation in low-resource settings. Deep learning-assisted telecytology diagnosis emerges as an appealing alternative, but it requires the collection of large annotated training datasets, which is costly and time-consuming. In this paper, we demonstrate that the abundance of unlabeled images that can be extracted from Pap smear test whole slide images presents a fertile ground for self-supervised learning methods, yielding performance improvements compared to off-the-shelf pre-trained models for various downstream tasks. In particular, we propose Cervical Cell Copy-Pasting (C3P) as an effective augmentation method, which enables knowledge transfer from public and labeled single-cell datasets to unlabeled tiles. Not only does C3P outperforms naive transfer from single-cell images, but we also demonstrate its advantageous integration into multiple instance learning methods. Importantly, all our experiments are conducted on our introduced in-house dataset comprising liquid-based cytology Pap smear images obtained using low-cost technologies. This aligns with our long-term objective of deep learning-assisted telecytology for diagnosis in low-resource settings.

Active screening for tuberculosis among high-risk populations in high-burden areas in Zhejiang province, China

ObjectivesTuberculosis (TB) is a major global public health concern. Although the incidence of TB in China is declining, the country continues to face many challenges regarding TB control. This study aimed to develop an active case finding (ACF) strategy for high-risk populations in areas with high TB burden and evaluate the effectiveness of the ACF strategy for early TB detection in patients to reduce TB transmission. Study designThis was a descriptive study. MethodsFrom May to October 2019, active TB screening was conducted in Zhejiang Province, China. Overall, 24 high-burden townships were chosen as study sites. Residents aged ≥65 years, suffering from diabetes, diagnosed with HIV/AIDS, or with a history of TB were mobilized for screening. Chest radiography was performed for all participants in the community. Sputum specimens were collected for sputum smear tests and cultures at county-level TB-designed hospitals. A professional medical team performed the final diagnoses. ResultsOverall, 130,643 residents were included, accounting for 8.85% of the total population in the selected areas. After screening, 89 confirmed cases and 419 suspected cases were identified. The detection rates for suspected and confirmed cases were 320.72/100,000 and 68.12/100,000, respectively. Individuals with a history of TB accounted for a large proportion of detected cases, and the detection rate was higher among males than in females. This study identified 10.5% of reported cases in the selected areas in 2019. In Zhejiang province, compared with the previous year, the rates of TB notification in 2019 and 2020 declined by 7.0% and 7.4%, respectively, compared with the previous year. However, the TB notification rate in 2019 was almost the same as that in 2018 (a decline of 2.5%) but sharply declined in 2020 (14.4%) in the screened areas. ConclusionsOur findings suggest that the ACF strategy may have helped to maintain the downward trends in TB notification rates by detecting patients with TB and suspected cases in the short term.

Two cases of vitamin B12 deficiency in patients with beta-thalassemia trait: lessons in diagnosis

BackgroundCoexisting pathologies is not a new phenomenon and can cause diagnostic difficulties when they overshadow one another. They may alter the cytomorphology of cells and the machine readings to an extent that the actual diagnosis is missed. One such scenario is created by coexisting megaloblastic anemia and beta-thalassemia trait where the RBC indices and the hemoglobin chromatogram findings conform to neither of the two. Case presentationWe present two cases of anemia presenting with normocytic normochromic indices, increased red cell distribution width (RDW), elevated HbA2 levels and moderately high HbF levels in both of them and an additional low HbA1c in case 2. Upon evaluation of peripheral smear and biochemical tests, a non-immune hemolytic component was also identified with deficient Vit B12 levels in case 1 and highly elevated levels post-supplementation in case 2. ConclusionsTaking together the peripheral smear, erythrogram, chromatogram and biochemical findings, it was deduced that the alterations were caused by coexisting beta-thalassemia trait and megaloblastic anemia. Vit B12 deficiency was the cause behind hemolysis owing to intramedullary destruction of abnormal precursors. Upon supplementation in case 2, the immediate reticulocyte response was the reason behind spuriously low HbA1c.

PI3K signaling promotes formation of lipid-laden foamy macrophages at the spinal cord injury site

After spinal cord injury (SCI), infiltrating macrophages undergo excessive phagocytosis of myelin and cellular debris, forming lipid-laden foamy macrophages. To understand their role in the cellular pathology of SCI, investigation of the foamy macrophage phenotype in vitro revealed a pro-inflammatory profile, increased reactive oxygen species (ROS) production, and mitochondrial dysfunction. Bioinformatic analysis identified PI3K as a regulator of inflammation in foamy macrophages, and inhibition of this pathway decreased their lipid content, inflammatory cytokines, and ROS production. Macrophage-specific inhibition of PI3K using liposomes significantly decreased foamy macrophages at the injury site after a mid-thoracic contusive SCI in mice. RNA sequencing and in vitro analysis of foamy macrophages revealed increased autophagy and decreased phagocytosis after PI3K inhibition as potential mechanisms for reduced lipid accumulation. Together, our data suggest that the formation of pro-inflammatory foamy macrophages after SCI is due to the activation of PI3K signaling, which increases phagocytosis and decreases autophagy.

The evolving role of intraneuronal amyloid‐β in Alzheimer’s disease

AbstractBackgroundIn 1998 at the Alzheimer’s Association conference in Amsterdam, I first presented on the accumulation of Alzheimer’s disease (AD)‐linked amyloid‐β42 (Aβ42) in cultured neurons and human brains with early AD pathology (later published in Gouras GK et al., 2000). Despite much skepticism, this early work led to a revision of the role of Aβ in AD that for the past 2.5 decades has been at the center of our group’s attempt to better define the earliest cellular stages of AD. Our current scenario, including with new data, will be presented for the role of intraneuronal Aβ in the early endosomal and synaptic alterations that initiate the disease process.MethodAD transgenic (overexpression and knock‐in) mouse models at different ages and postmortem human brains are analyzed using amongst others, microscopy and biochemical approaches for APP metabolites, and other AD‐linked, endosome and synapse proteins, with a focus on the earliest detectable alterations within AD vulnerable neurons. Brain injections of prion‐like Aβ and tract tracing methods are used to model early anatomical and cellular progression of pathology. Further, primary brain cultures from AD mice are used to model early AD cellular alterations.ResultPrior to classical amyloid plaques, smaller accumulations of Aβ develop within the endosome‐lysosome system of AD vulnerable neurons, with preferential aggregation near axonal and dendritic synaptic terminals with AD pathogenesis. Ongoing work is centered on elucidating the early alterations of different pools of APP metabolites, ApoE and Tau in the early biological pathways that impact synapses.ConclusionOur understanding of the early cellular dysfunction and pathology has evolved significantly over the past few decades, with a better appreciation for the importance of other cell types (e.g. astrocytes, microglia) and factors in AD, and recent, albeit modest, success in therapy targeting Aβ. We see aging, along with genes and lifestyle, as promoting the earliest Aβ‐related dysfunction in endosomal biology at synapses and are working to piece together the links between key AD‐related proteins in the disease process.

Human Papillomavirus among Women Undergoing Papanicolaou Smear Test in the Department of Gynaecologic Oncology of a Tertiary Care Centre.

In invasive cervical specimens or precursors, high-risk human papillomavirus Deoxyribonucleic acid may be detected to identify females at risk of developing cervical cancer. This study aimed to find out the prevalence of human papillomavirus among women undergoing Papanicolaou smear tests in a tertiary care centre. A descriptive cross-sectional study was conducted among women undergoing the Papanicolaou smear test in the Department of Gynaecologic Oncology, Nepal Armed Police Force Hospital, between 1 June 2022 and 15 November 2022. Ethical approval was obtained from the Ethical Review Board. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Among the 199 women, 6 (3.02%) (0.64-5.40, 95% Confidence Interval) had human papillomavirus infection. The mean age of the infected females was 31.17±5.57 years. Human papillomavirus DNA for 16 and 18 were detected in 4 (66.67%) and 2 (33.33%) females, respectively. The prevalence of human papillomavirus in females was found to be lower than other studies done in similar settings. cytology; histology; human papillomavirus; Nepal; prevalence.