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Immunity Feb 2024Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas...
Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas of the human tonsil composed of >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well as spatial transcriptomics. This census identified 121 cell types and states, defined developmental trajectories, and enabled an understanding of the functional units of the tonsil. Exemplarily, we stratified myeloid slan-like subtypes, established a BCL6 enhancer as locally active in follicle-associated T and B cells, and identified SIX5 as putative transcriptional regulator of plasma cell maturation. Analyses of a validation cohort confirmed the presence, annotation, and markers of tonsillar cell types and provided evidence of age-related compositional shifts. We demonstrate the value of this resource by annotating cells from B cell-derived mantle cell lymphomas, linking transcriptional heterogeneity to normal B cell differentiation states of the human tonsil.
Topics: Humans; Adult; Palatine Tonsil; B-Lymphocytes
PubMed: 38301653
DOI: 10.1016/j.immuni.2024.01.006 -
International Journal For Parasitology.... Apr 2024The ectoparasitic seal louse, infects harbour () and grey seals () in the North and Baltic Sea. The endoparasitic heartworm parasitizes the right heart and blood...
The ectoparasitic seal louse, infects harbour () and grey seals () in the North and Baltic Sea. The endoparasitic heartworm parasitizes the right heart and blood vessels of harbour seals. The complete lifecycle of the heartworm is not entirely understood although the seal louse is assumed to serve as vector for its transmission. Knowledge about the impact of both parasite species on host health are scarce. In this study, necropsy data and archived parasites of harbour and grey seals in German waters were analysed to determine long-term seal louse (SLP) and heartworm prevalence (HWP) from 2014 to 2021. Histology, microbiology and scanning electron microscopy (SEM) were applied on seal louse infected and uninfected skin to investigate associated lesions and the health impact. During the study period, HWP in harbour seals was 13%, the SLP in harbour seals was 4% and in grey seals 10%. HWP of harbour seals was significantly higher during the winter months compared to the summer. SLP in adults was significantly higher in comparison to juvenile harbour seals. SLP varied significantly between grey seals from the North and Baltic Sea. Filarial nematodes were detected in the haemocoel, pharynx, and intestine of highlighting the seal louse as vector for heartworms. Alopecia and folliculitis were associated with the attachment posture of and microbiological investigations isolated bacteria commonly associated with folliculitis.
PubMed: 38283886
DOI: 10.1016/j.ijppaw.2023.100898 -
Journal of Cytology 2024Cancer is a leading cause of death worldwide and is a major cause of morbidity. To deal with this magnitude of cancers and their diagnostic and prognostics, a multitude...
INTRODUCTION
Cancer is a leading cause of death worldwide and is a major cause of morbidity. To deal with this magnitude of cancers and their diagnostic and prognostics, a multitude of prognostic biomarkers for various cancers have been explored over the decades, with detection of circulating tumor cells (CTCs) in the peripheral blood being one of them. This study was undertaken to explore the routine procedure of cell block in the cytopathology lab to isolate and detect CTCs.
MATERIALS AND METHODS
In this cross-sectional study, 112 peripheral blood samples sent for routine blood investigations of various cancer patients were utilized for the preparation of cell block. The sections from the cell block were stained routinely and evaluated for the presence of CTCs. The statistical analysis was done using Mac Statplus software version 8.0.
RESULTS
The malignancies were tabulated as per the International Classification of Diseases for Oncology, third edition (ICD-O-3). The maximum number of cases were from C 50 (breast) - 41/112 (36.6%), followed by C15-C26 (Digestive organs) - 19/112 (16.9%), and C00-C14 (lip, oral cavity, and pharynx) - 18/112 (16.07%) cases. CTC was detected in six (5.35%) out of 112 cases, out of which three were from the breast and one each from category C6.9 (mouth), C32.0 (glottis), and C53.8 (cervix uteri).
CONCLUSION
Among various advanced and molecular techniques available for the detection of CTCs, the cell block technique proves to be one of the effective methods, especially in resource-limited settings as these can further be utilized for additional diagnostic techniques similar to the ones employed for routine paraffin blocks.
PubMed: 38282811
DOI: 10.4103/joc.joc_123_23 -
Scientific Reports Jan 2024CD4 T cells play a key role in Epstein Barr virus (EBV) infection, by modulating latent antigen expression, and exhibiting cytotoxic and regulatory properties. Our aim...
CD4 T cells play a key role in Epstein Barr virus (EBV) infection, by modulating latent antigen expression, and exhibiting cytotoxic and regulatory properties. Our aim was to evaluate the presence of Granzyme B (GZMB) and Foxp3 CD4 T cells at different EBV infection status and latency profiles. We examined CD4, GZMB, Foxp3, IL10, TGF-β, CD4-GZMB and CD4-Foxp3 expression at the tonsils of pediatric patients with different infective status and EBV latency profiles. CD4+, GZMB+, Foxp3+, CD4-GZMB+ and CD4-Foxp3+ cell counts were higher at the interfollicular region. Higher expression of CD4-GZMB was found in primary infected patients compared to healthy carriers. In patients that expressed latency III antigens, we demonstrated lower CD4+, CD4-GZMB+, CD4-Foxp3+ expression; a negative correlation between the immunoregulatory cytokine IL-10+ and GZMB+ as well as a positive correlation of IL-10+ and CD4+. In patients expressing the lytic protein BMRF1, a positive correlation of TGF-β+ with CD4-GZMB+ and CD4-Foxp3+ was observed. Our findings indicate that CD4-GZMB+ cells are involved in the restriction of primary EBV infection in pediatric patients, which could partially explain the lack of symptoms, whereas both CD4-GZMB+ and CD4-Foxp3+ cells could be involved in the modulation of latency.
Topics: Humans; Child; Epstein-Barr Virus Infections; Herpesvirus 4, Human; CD4-Positive T-Lymphocytes; Interleukin-10; Palatine Tonsil; Transforming Growth Factor beta; Forkhead Transcription Factors
PubMed: 38273012
DOI: 10.1038/s41598-024-52666-4 -
Scientific Reports Jan 2024There are few pertinent studies about the application of laryngeal mask airways (LMAs) in lateral decubitus surgery. Therefore, the aim of our study was to evaluate the... (Randomized Controlled Trial)
Randomized Controlled Trial
There are few pertinent studies about the application of laryngeal mask airways (LMAs) in lateral decubitus surgery. Therefore, the aim of our study was to evaluate the effects of lateral position and pneumoperitoneum on oropharyngeal leak pressure (OLP) and ventilation efficiency for the LMA SaCoVLM. Patients undergoing elective retroperitoneal laparoscopic urological surgery were randomized 1:1 to the Supreme group or SaCoVLM group. The primary outcome was the OLP with LMA insertion. The secondary outcomes were the first-attempt success rate, insertion time, adjustment times, gastric tube success rate, LMA alignment accuracy, LMA removal time, regurgitation or aspiration, LMA blood staining, and incidence of adverse events 24 h after surgery. We recruited 70 patients to complete the study. Regardless of lateral position and pneumoperitoneum, the OLP was greater in the SaCoVLM group (n = 35) than in the Supreme group (n = 35), with a median difference of 4-7 cmHO. The first-attempt success rate of the SaCoVLM group was higher than that of the Supreme group (91.4% vs. 77.1%, risk ratio (RR): 1.19; 95% CI 0.96 to 1.46, P = 0.188). Thus, in the lateral position with pneumoperitoneum, although the new video LMA SaCoVLM has a higher OLP than the LMA Supreme, both devices provide sufficient ventilation efficiency.
Topics: Humans; Laparoscopy; Laryngeal Masks; Oropharynx; Pneumoperitoneum; Pressure
PubMed: 38272937
DOI: 10.1038/s41598-024-51856-4 -
BMC Anesthesiology Jan 2024Dyclonine hydrochloride mucilage is a topical anaesthetic formulated for mucosal surfaces. It is employed frequently for topical anaesthesia of the pharynx prior to...
BACKGROUND
Dyclonine hydrochloride mucilage is a topical anaesthetic formulated for mucosal surfaces. It is employed frequently for topical anaesthesia of the pharynx prior to endoscopic examinations such as electronic gastroscopy, and few adverse reactions have been reported. This article describes a patient who experienced a transient but severe disturbance of consciousness following oral dyclonine hydrochloride mucilage administration.
CASE PRESENTATION
A 75-year-old female presenting with gastrointestinal bleeding was examined by electronic gastroscopy. Six minutes after oral dyclonine hydrochloride mucilage administration, the patient entered a comatose-like state accompanied by loss of limb muscle tone and profuse perspiration. This response was not accompanied by changes in cardiac rhythm, blood pressure, or respiration rate, suggesting an effect on higher brain centres. After ten minutes, the patient's symptoms were alleviated.
CONCLUSION
We suggest that sites of dyclonine hydrochloride mucilage use be equipped with appropriate rescue devices for these rare events.
Topics: Female; Humans; Aged; Consciousness; Brain; Administration, Oral; Anesthesia, Local; Propiophenones
PubMed: 38254013
DOI: 10.1186/s12871-024-02407-x -
Saudi Medical Journal Jan 2024To study the mechanisms of injury, clinical manifestations, radiological findings, management, and outcomes of traumatic retropharyngeal hematoma (RH).
OBJECTIVES
To study the mechanisms of injury, clinical manifestations, radiological findings, management, and outcomes of traumatic retropharyngeal hematoma (RH).
METHODS
We used the Preferred Reporting Items of Systematic Reviews guidelines to carry out a systematic literature review to identify all published cases of traumatic RH by searching the PubMed database. Articles published between 1988 and 2022 that reported traumatic RH were included. However, articles that reported non-traumatic RHs and non-English articles were excluded from this study.
RESULTS
Of the 62 articles screened, 56 were included. Most patients (55%) were above the mean age of 61.7. The majority of patients were male (69.7%). The main symptom was dyspnea (66.6%) and symptoms usually presented within 24 hours. Among the patients, 90.9% did not take anticoagulants or have coagulation disorders, and the main injury mechanism was falling (54.5%). Most of the computed tomography findings reported retropharyngeal (38%) and prevertebral (15%) hematoma. Meanwhile, magnetic resonance imaging revealed 2 masses in the retropharyngeal space and 2 RHs. With several treatment modalities, more than 50% of the cases were only observed (44 cases), and endotracheal intubation was the most commonly used airway management method (n=35).
CONCLUSION
Traumatic RH is often caused by falls, particularly in elderly patients. Dyspnea is the primary symptom, usually appearing within 24 hours. Cervical vertebral fractures are the leading cause, and observation is the most common treatment approach..
Topics: Aged; Female; Humans; Male; Middle Aged; Dyspnea; Hematoma; Pharyngeal Diseases; Spinal Fractures; Systematic Reviews as Topic
PubMed: 38220242
DOI: 10.15537/smj.2024.45.1.20230565 -
Cell Reports Methods Jan 2024The molecular and immunological properties of tissue-resident resting CD4 T cells are understudied due to the lack of suitable gene editing methods. Here, we describe...
The molecular and immunological properties of tissue-resident resting CD4 T cells are understudied due to the lack of suitable gene editing methods. Here, we describe the ex vivo culture and gene editing methodology ediTONSIL for CD4 T cells from human tonsils. Optimized CRISPR-Cas9 RNP nucleofection results in knockout efficacies of over 90% without requiring exogenous activation. Editing can be performed on multiple cell types in bulk cultures or on isolated CD4 T cells that can be labeled and reintroduced into their tissue environment. Importantly, CD4 T cells maintain their tissue-specific properties such as viability, activation state, or immunocompetence following reassembly into lymphoid aggregates. This highly efficient and versatile gene editing workflow for tonsillar CD4 T cells enables the dissection of molecular mechanisms in ex vivo cultures of human lymphoid tissue and can be adapted to other tonsil-resident cell types.
Topics: Humans; CD4-Positive T-Lymphocytes; Palatine Tonsil; Gene Editing; Lymphoid Tissue
PubMed: 38211593
DOI: 10.1016/j.crmeth.2023.100685 -
Animals : An Open Access Journal From... Dec 2023Osteoarthritis is a degenerative articular disease affecting mainly aging animals and people. The extracellular matrix protein Efemp1 was previously shown to have higher...
Osteoarthritis is a degenerative articular disease affecting mainly aging animals and people. The extracellular matrix protein Efemp1 was previously shown to have higher turn-over and increased secretion in the blood serum, urine, and subchondral bone of knee joints in osteoarthritic patients. Here, we use the zebrafish as a model system to investigate the function of Efemp1 in vertebrate skeletal development and homeostasis. Using in situ hybridization, we show that the gene is expressed in the brain, the pharyngeal arches, and in the chordoblasts surrounding the notochord at 48 hours post-fertilization. We generated an mutant line, using the CRISPR/Cas9 method, that produces a severely truncated Efemp1 protein. These mutant larvae presented a medially narrower chondrocranium at 5 days, which normalized later at day 10. At age 1.5 years, µCT analysis revealed an increased tissue mineral density and thickness of the vertebral bodies, as well as a decreased distance between individual vertebrae and ruffled borders of the vertebral centra. This novel defect, which has, to our knowledge, never been described before, suggests that the mutant represents the first zebrafish model for spinal osteoarthritis.
PubMed: 38200805
DOI: 10.3390/ani14010074 -
Journal of Neurosurgery. Case Lessons Jan 2024Extracranial internal carotid artery aneurysms (EICAs) are rare. Although a high mortality risk has been reported in nonoperated cases, the optimal treatment for EICAs...
Recurrence of an extracranial internal carotid artery aneurysm treated with STA-MCA bypass and trapping due to neovascularization from an ascending pharyngeal artery: illustrative case.
BACKGROUND
Extracranial internal carotid artery aneurysms (EICAs) are rare. Although a high mortality risk has been reported in nonoperated cases, the optimal treatment for EICAs remains unknown.
OBSERVATIONS
A 79-year-old female presented with painless swelling in the right neck. Imaging revealed a giant EICA with a maximum diameter of 3.2 cm. Superficial temporal artery-middle cerebral artery bypass and internal carotid artery (ICA) trapping were performed. Because the distal aneurysm edge was at the C1 level, the distal portion of the aneurysm was occluded by endovascular coiling, and the proximal portion was surgically ligated. Blood flow into the aneurysm disappeared after the operation. Three years postsurgery, enlargement of the aneurysm with blood flow from the ascending pharyngeal artery (APA) was detected. The EICA was resected after coiling the APA and ligating both ends of the aneurysm. Pathologically, neovascularization within the aneurysm wall was observed.
LESSONS
Even if blood flow into an EICA disappears after ICA trapping, the EICAs can enlarge due to neovascularization from the neighboring artery. From the outset, removal of the aneurysm should be considered as a radical treatment strategy for giant EICAs.
PubMed: 38190660
DOI: 10.3171/CASE23617