Background: Aneurysmal bone cyst (ABC) is a benign but locally aggressive bone lesion. USP6 gene rearrangements have been proposed as a key diagnostic marker, detectable via fluorescence in situ hybridization (FISH). However, its clinical utility and correlation with recurrence remains unclear. This study evaluates USP6 FISH as a diagnostic tool and investigates whether USP6 positivity is associated with an increased recurrence risk. Materials & methods: This retrospective study analyzed 87 patients with primary ABC at Klinikum rechts der Isar, Technical University of Munich (1991–2021). Histopathological and radiological criteria were used for diagnosis, with USP6 FISH testing performed on available specimens. Statistical analyses, including Kaplan–Meier recurrence estimates and Cox regression were conducted to assess the association between USP6 status and recurrence. Conclusion: USP6 FISH is a highly specific but moderately sensitive tool for diagnosing primary ABC. While a positive USP6 result supports the diagnosis, clinical and histopathological correlation remains essential. Importantly, USP6 positivity showed no significant correlation with recurrence, suggesting that surgical factors play a larger role. These findings confirm the diagnostic relevance of USP6 FISH but indicate that recurrence risk should be assessed independently of molecular status.
In this study, the rectus sheath and amniotic membrane were utilized to repair tunica albuginea damage in rabbits. Ten male New Zealand white rabbits were included in the study. Group 1 consisted of 5 rabbits in which the tunica albuginea injury was repaired using amniotic membrane from pregnant rabbits. Group 2 consisted of 5 rabbits in which their rectus sheath was used to repair the tunica albuginea injury. Our results showed that both the use of amniotic membrane and rectus sheath are effective in repairing tunica albuginea damage in rabbits. Based on our macroscopic and microscopic findings, there was no statistically significant difference between the effectiveness of amniotic membrane and rectus sheath in repairing tunica albuginea damage. Both the amniotic membrane and the rectus sheath were equally effective in repairing tunica albuginea damage.
The pancreatic islets of Langerhans contain a minority of endocrine cells that contain more than one hormone: predominantly combinations of glucagon, insulin and somatostatin. A recent paper from our laboratory examined the ontogeny of such cells in the human pancreas and found that they persisted throughout the lifespan but altered in relative abundance with age. Glucagon/insulin bi-hormonal cell number significantly increased with age whilst insulin/somatostatin and glucagon/somatostatin cells significantly decreased. Building on that study here we explore the possible origins and physiological role of bi-hormonal cells within the endocrine pancreas. During pancreas development in utero mono-hormonal endocrine cell lineages are defined by distinct signatures of transcription factor expression. Insufficient or inappropriately timed expression in sub-populations of endocrine cell progenitors may fail to suppress genes normally restricted to other endocrine cell types, resulting in residual populations of bi-hormonal cells. These have been identified postnatally by single cell transcriptomic or proteomic analysis and do not appear to have a metabolic role distinct from that of mono-hormonal cells. However, during hyperglycemic stress bi-hormonal cell sub-populations can proliferate and transdifferentiate into new beta-cells capable of glucose-stimulated insulin release. Transdifferentiation is reversible and in both type 1 and 2 diabetes some beta-cells can dedifferentiate to form hormone-null cells or alpha-cells. Thus, current evidence suggests that diverse phenotypic pools of endocrine cell phenotypes are retained within the islets into adult life that can undergo lineage changes in response to metabolic demand. There is preliminary evidence that these pathways can be therapeutically manipulated.
Aquatic prokaryotic cyanobacteria (algal blooms) produce cyanotoxins (CTs), significant pollutants in aquatic ecosystems. Direct exposure to high-concentration CTs through inhalation, skin contact, or ingestion of contaminated water can lead to hepatotoxicity and neurotoxicity. However, the effect of exposure to CTs at low concentrations remains unclear. Given that CTs can cross the blood-brain barrier via organic anion transporting polypeptides (OATPs), we investigated the effect of acute exposure to low concentrations (10 nM and 50 nM) of CTs, namely microcystin-LR (MC-LR), nodularin (NOD), cylindrospermopsin (CYN), and known neurotoxin β-N-methylamino-l-alanine (BMAA) in neuroblastoma SH-SY5Y cells. Using MTT assays, we found that all tested CTs increased cell survival at low concentrations. MC-LR, NOD, and CYN regulated the expression of metabolic CYP1A1, CYP1A2, CYP2D6, CYP2E1, CYP3A4, and VEGFA expression differentially, whereas BMAA downregulates metabolic gene expression. CT exposure downregulates mitochondrial oxygen consumption rate in neuroblastoma SH-SY5Y cells, increases IL-6, SOD1, and TNFα expression, and enhances cell apoptosis. CTs also downregulated unfolded protein response-associated gene expression and increased Tau phosphorylation. Collectively, these findings suggest that acute exposure to low concentrations of CTs modulates neuroblastoma cell metabolism, Inflammatory signaling, and AD-related markers, highlighting a potential link between environmental toxin exposure and neurotoxicity.
The pathological evaluation of ovaries is a critical endpoint in reproductive toxicology assessments. Currently, there is no standardized method for the quantification of oocytes and follicles in preclinical drug safety evaluations. This study developed a simplified quantitative method based on stereological principles to efficiently assess the number of oocytes in experimental rabbits. The quantitative results obtained with this method are consistent with those from traditional counting methods. This innovative approach reduces the time of slide preparation and cell quantification, making it efficient for evaluating oocyte quality in large scale of toxicity studies.
Congenital melanocytic nevi (CMN) are benign melanocytic neoplasms that vary in genetic drivers leading to the formation of pigmented lesions. Activation of Mitogen-Activated Protein Kinase (MAPK) pathway members through oncogenic mutations of NRAS or BRAF and more rarely by gene fusions allow expansion of nevomelanocytes to form CMN. Pre-clinical approaches to CMN therapy are expanding with the use of small-molecular inhibitors to mitogen-activated protein kinase kinase (MEK), RNA-based therapeutic approaches, and leveraging topical immunotherapy to regress nevi using in vitro and in vivo models and select case reports. Continued identification of CMN drivers combined with emerging therapeutic strategies will help improve CMN patient response and outcomes in the future.
Background: Brain tumors exhibit significant molecular heterogeneity, complicating diagnosis, prognosis, and treatment. Traditional tissue biopsies are invasive and often fail to capture the full tumor landscape due to intratumoral heterogeneity. Liquid biopsy, which analyzes cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA), offers a minimally invasive alternative for tumor profiling. Nanopore sequencing, a novel long-read sequencing technology, is emerging as a valuable tool in this context. Purpose: This review explores the application of nanopore sequencing in molecular profiling of brain tumors using liquid biopsy, focusing on its ability to detect both genetic and epigenetic alterations with clinical relevance. Main body: Brain tumors, such as gliomas and medulloblastomas, are characterized by diverse molecular profiles, which influence patient outcomes and treatment strategies. Nanopore sequencing offers unique advantages for profiling cfDNA from biofluids like cerebrospinal fluid (CSF) and plasma, including the ability to generate long reads and detect structural variants, copy number alterations, and methylation patterns. Several studies have demonstrated its potential to identify key mutations (e.g., IDH1/2, H3K27 M) and track tumor evolution through serial cfDNA monitoring. However, challenges remain, including low ctDNA fractions in biofluids and bioinformatic complexities. Conclusion: Nanopore sequencing holds significant promise for advancing non-invasive molecular profiling of brain tumors, offering real-time insights into tumor genomics and evolution. This technology could revolutionize personalized brain tumor management, but further validation and optimization are needed before it can be routinely applied in clinical practice.
With the increasing need for targeted therapies in non-small cell lung carcinoma (NSCLC), preserving sufficient biopsy material has become essential. As most lung cancer cases are advanced or inoperable at the time of diagnosis, small biopsies, including cytology specimens, often serve as the only source of diagnostic material. Accurate subclassification of adenocarcinoma and squamous cell carcinoma in NSCLC using a limited panel including TTF1 and p63/p40 immunohistochemical (IHC) staining, as well as confirming small cell carcinoma using essential IHC markers, is critical for precise diagnosis, cost-effective treatment, and optimal patient care. This review highlights common challenges in applying IHC to small lung biopsies, focusing on diagnostic pitfalls from real-world cases, including adenocarcinoma, squamous cell carcinoma, and the use of IHC markers to support neuroendocrine carcinoma diagnosis. Together, these entities account for over 94% of all lung cancers, according to 2024 cancer statistics. Relevant clinical information, epidemiology, and molecular mechanisms will also be discussed for comprehensive practice considerations. The goal is to raise awareness among practicing pathologists about the critical role of IHC applications in small lung biopsies, with the aim of improving patient care by minimizing unnecessary IHC use while ensuring accurate diagnoses.
Preserving the integrity of the auditory system is crucial for language development, learning, and social interaction. Any interruption in these processes during development can result in significant functional impairments. The objective was to carry out a longitudinal analysis of audiological data from children who underwent an initial assessment at SASA in 2018 and were followed up for 4 years at the outpatient's annual consultations. This is a retrospective cross-sectional study with children who underwent initial assessment for hearing loss and follow-up at a reference service for the Unified Health System (SUS), from January 2018 to December 2022. Children aged 0 to 12 years old who underwent an initial assessment for hearing loss and follow-up in the service's database, where secondary data analyses will be carried out. Data from 127 subjects with an average age of 20 months were analyzed. 60.62% of the subjects were diagnosed with some degree of hearing loss, and the etiology of the change remained unknown in 29.90% of the cases. A considerable percentage of subjects remained under follow-up during annual consultations. There was good adherence to annual returns and follow-ups at the outpatient clinic, indicating a high attendance rate.
Cell competition is a conserved phenomenon spanning from arthropods to humans. It involves the elimination of viable yet suboptimal "loser" cells when juxtaposed with their fitter "winner" counterparts. This process has received increased attention for its implications in cancer initiation and progression, neurodegeneration, and ageing. This study investigates the presence of the loser fitness fingerprint Flower LoseB (Fwe LB) and the fitness checkpoint Azot in the optic lobes over a period of 28 days. Notably, the absence of Azot is conventionally linked to the accumulation of loser cells over time. However, our investigation reveals that this accumulation is not perpetual and, intriguingly, Azot is not required for loser cell elimination in this context because loser cells are still eliminated by apoptosis in its absence. Furthermore, we wanted to clarify the percentage of loser cells that are eliminated, and the percentage of dying cells identified as loser during cell competition. We estimate that fewer than 50% of Fwe LB-expressing cells also express Azot and undergo apoptosis. Remarkably, our calculations also demonstrate that over 50% of cells undergoing apoptosis at any given time point are positive for the loser markers Fwe LB and Azot, stressing the relevant role of cell competition in promoting the elimination of suboptimal cells. This comprehensive analysis of fitness marker dynamics over a 28-day timeframe sheds new light on the intricate mechanisms governing Flower-dependent cell competition.
As pure science, pathology has always been the backbone of every aspect of diagnosis in medical practice. Although the main focus has been on the classification of the disease entities and their association with the prognosis of the condition
OBJECTIVE:To verify the frequency of risk factors for hearing loss in newborns and their possible associations with universal neonatal hearing screening results before and during the COVID-19 pandemic. METHODS:Historical cohort study with data analysis of newborns attended in a reference hearing health service of the Unified Health System (SUS) between January 2017 and December 2021. RESULTS:Those born in 2020 and 2021 were 91% less likely to fail the screening than those born in 2017, 2018, and 2019; therefore, they had a lower percentage of referrals for a retest. There was a decrease in congenital syphilis (1.00%), decrease in HIV (0.95%), and an increase in toxoplasmosis (0.58%) and increase in rubella cases in 2021 in relation to 2017. Syphilis had lower frequency rates during the COVID-19 pandemic (2020-2021). CONCLUSION:Newborns born in the pandemic year compared to those born pre-pandemic showed a reduction in the presence of two risk indicators for hearing loss and, consequently, a lower chance of failing the UNHS and a lower percentage of referral for retest.
Introduction: Fine needle aspiration cytology (FNAC) is a first-line investigation for palpable lumps and is a highly cost-effective and accurate investigative technique. It is a safe, simple, rapid, minimally invasive technique. Liquid-based cytology (LBC) has been used in gynecologic-cytology for over three decades. Many laboratories have adopted LBC technique for exfoliative and FNA samples. We undertook the present study to compare the advantages and disadvantages of conventional and liquid based cytology preparations. Aim of the study: To evaluate the diagnostic accuracy of LBC and Conventional smears in fine needle aspiration cytology samples from breast, lymph nodes, and thyroid tissue. Materials and methods: FNA material from accessible sites such as palpable breast lumps, thyroid, and lymph nodes were collected from 100 patients and was processed by two different methods, i.e., Conventional smears and by LBC. Various parameters on the slides were considered and compared for both the preparations. Out of 100 FNA samples, 51% were of Thyroid, 34% were of lymph node and 15% were of breast lumps. Observations and results: Adequate cellularity and better architecture was present in conventional smears than LBC preparations. Background material was less, and monolayers were better in the LBC preparations. Informative background material (i.e. Colloid, lymphoglandular bodies, etc) was more in cases of Conventional smears. The nuclear and cytoplasmic details were nearly equally good in both the preparations. Conclusion: Both these methods have their own advantages and disadvantages. Before incorporating LBC as a routine method, pathologists should familiarize themselves with all the aspects of LBC.
From last few decades, microbes gained special attention residing inside plant tissues, now called endophyte. Studies proved that these microbes are able to produce biologically active metabolites and effective candidates against various pathogens. Endophytic fungi are a source of natural therapeutic products. Therefore, endophytic Fusarium species are isolated from different plants. These endophytic Fusarium species showed a potential against common laboratory bacteria (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhimurium and Bacillus subtilis). Fusarium moniliforme and Cephalosporium sp., were further selected to isolate compounds by GC-MS techniques. The mycelial extract of Cephalosporium sp., and oily fraction of filtrates of F. moniliforme revealed the presence of several therapeutic compounds based on the peak areas, molecular weights, Rt (retention times) and m/z (mass fragmentations). The major bioactive metabolites identified from these fungi are Cholest-22-ene-21-ol, 3,5-dehydro-6-methoxy-pivalate, Salicylamide, 1,2-Benzenedicarboxylic acid, Geranyl isovalerate, and diisooctyl ester, and reported to possess antibacterial, antioxidant, nematicidal, and antifungal potential. These results will lead to further in-depth research into the potential cause of plants endophytes interactions. The wide application of fungal origin bio products offers an effective prospect for discovering novel therapeutic agents in order to combat infectious agents as well as agricultural pests.
Chlamydia trachomatis is a bacterial infection that most frequently causes sexually transmitted infection in the world, therefore, it is considered a serious public health problem. The objective of this commentary is to describe in a condensed but sufficient manner what has been reported by researchers on the subject based on the documentary review available in digital repositories on aspects of the infection. The information obtained was grouped into 7 categories as a result of the analysis of relevant ideas. There are many aspects to be revealed in terms of pathogenesis, biology of the microbial agent, and treatment, hence the need to generate new knowledge in this regard and to carry out thematic consolidations such as the one presented here.
Our previous research demonstrated that TERT and concurrent PIK3CA mutations predict worse overall survival in patients with poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma. However, the molecular mechanism underlying the synergistic oncogenic operations of the two oncogenes is unclear. This study aimed to explore further the effect of TERT and PIK3CA co-mutation on the malignant biological phenotype of thyroid carcinoma and its possible mechanism. PIK3CA E545K mutation plasmid was transfected into thyroid anaplastic cancer cell line (C643) with TERT promoter mutation, then CCK-8 and transwell invasion assays were used to investigate the ability of cell proliferation and invasion, respectively. RT-qPCR and western blot were performed to detect the expression of PIK3CA, TERT, GABPA and GABPB1. GABPA/GABPB1 siRNA plasmid was transfected with C643 cells, then the ability of cell proliferation and invasion were identified. We also detected the expression of PIK3CA and TERT. C643 cells carry TERT promoter mutation C228T. Concurrent PIK3CA E545K and TERT mutation markedly enhanced the proliferation and invasion of C643 cell in vitro, with significantly increased mRNA/protein expression of PIK3CA, TERT, GABPA and GABPB1. Knocking down GABPA markedly inhibited cell proliferation. Knocking down of GABPB1 significantly decreased the proliferation and invasion of C643 cells, with much lower expression of PIK3CA and TERT. TERT and PIK3CA co-mutations promote the proliferation and invasion of thyroid anaplastic carcinoma cells and may be caused by up-regulating the expression of GABPA and GABPB1.
