Enteric glia regulate Paneth cell secretion and intestinal microbial ecology.

Glial cells of the enteric nervous system (ENS) interact closely with the intestinal epithelium and secrete signals that influence epithelial cell proliferation and barrier formation in vitro. Whether these interactions are important in vivo, however, is unclear because previous studies reached conflicting conclusions [1]. To better define the roles of enteric glia in steady state regulation of the intestinal epithelium, we characterized the glia in closest proximity to epithelial cells and found that the majority express PLP1 in both mice and humans. To test their functions using an unbiased approach, we genetically depleted PLP1+ cells in mice and transcriptionally profiled the small and large intestines. Surprisingly, glial loss had minimal effects on transcriptional programs and the few identified changes varied along the gastrointestinal tract. In the ileum, where enteric glia had been considered most essential for epithelial integrity, glial depletion did not drastically alter epithelial gene expression but caused a modest enrichment in signatures of Paneth cells, a secretory cell type important for innate immunity. In the absence of PLP1+ glia, Paneth cell number was intact, but a subset appeared abnormal with irregular and heterogenous cytoplasmic granules, suggesting a secretory deficit. Consistent with this possibility, ileal explants from glial-depleted mice secreted less functional lysozyme than controls with corresponding effects on fecal microbial composition. Collectively, these data suggest that enteric glia do not exert broad effects on the intestinal epithelium but have an essential role in regulating Paneth cell function and gut microbial ecology.

Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and CXCL10.

The interplay among different cells in a tissue is essential for maintaining homeostasis. Although disease states have been traditionally attributed to individual cell types, increasing evidence and new therapeutic options have demonstrated the primary role of multicellular functions to understand health and disease, opening new avenues to understand pathogenesis and develop new treatment strategies. We recently described the cellular composition and dynamics of the human oral mucosa; however, the spatial arrangement of cells is needed to better understand a morphologically complex tissue. Here, we link single-cell RNA sequencing, spatial transcriptomics, and high-resolution multiplex fluorescence in situ hybridisation to characterise human oral mucosa in health and oral chronic inflammatory disease. We deconvolved expression for resolution enhancement of spatial transcriptomic data and defined highly specialised epithelial and stromal compartments describing location-specific immune programs. Furthermore, we spatially mapped a rare pathogenic fibroblast population localised in a highly immunogenic region, responsible for lymphocyte recruitment through CXCL8 and CXCL10 and with a possible role in pathological angiogenesis through ALOX5AP. Collectively, our study provides a comprehensive reference for the study of oral chronic disease pathogenesis.

Divergent Schwannoma-Like Phenotype in a Pleomorphic Adenoma.

The schwannoma-like pleomorphic adenoma is a rare histopathological variant of the pleomorphic adenoma. Five previous reports with seven cases exist in English language literature. These tumors present in the parotid gland most commonly. Intraparotid schwannomas of the facial nerve and schwannomas with glandular differentiation have also been reported. A 60-year-old male presented with an asymptomatic swelling over the left angle of the mandible. The swelling had been present for about 12 years with a recent increase in size. CT imaging showed a hyperdense circumscribed mass of the superficial lobe of the parotid. The working diagnosis was that of a benign tumor of salivary gland or soft tissue origin. The mass was excised with careful preservation of the facial nerve. The 3.5 cm mass was submitted for histopathological examination. The well-circumscribed, encapsulated mass showed a predominant sheet-like proliferation of Antoni type A-like tissue, Foci of glandular differentiation with duct-like structures were also seen. Cytological atypia or mitotic activity were not seen. Nuclei of lesional cells diffusely and strongly expressed reactivity to p63. The final diagnosis was a schwannoma-like pleomorphic adenoma. No recurrence has been reported in the 15 months since the removal. Facial nerve function is unimpaired with a House Brackmann facial nerve function score of one. The potential for misdiagnosis in fine needle aspirate and incisional biopsies is real in cases of schwannoma-like pleomorphic adenoma. The diagnostic pitfalls include the schwannoma and leiomyoma. Schwannomas with glandular differentiation have also been reported and therefore a misdiagnosis may potentially occur in excised specimens. Careful application of immunohistochemistry may help in the differentiation of these lesions.

Maternal morbidity in emergency versus elective caesarean section at a tertiary care hospital.

BACKGROUND: In the past 30 years the rate of caesarean section (C/S) has steadily increased from 5% to more than 20% for many avoidable and unavoidable indications. The objective of this study was to compare maternal morbidity and determine its cause in elective and emergency caesarean section. METHOD: It was a cross-sectional comparative study conducted in Civil Hospital Karachi at Obs/Gyn Unit III. All mothers admitted through OPD or emergency during the study period, of any age or parity undergoing C/S were recruited in the study. Patients having previous myomectomy, hysterotomy or classical C/S were excluded from the study. Patients undergoing emergency C/S were placed in group A, and those delivered by elective C/S were included in group B. Study variables were general and obstetric parameters and complications observed intra-operatively. Any postoperative complications were recorded from recovery room till patient was discharged from the ward. RESULTS: There were 50 patients in each group. In group A, 11 (22%) were booked and 33 (66%) were referred cases. In group B, 48 (96%) were booked. The mean age in both groups was 28 years. In both groups, multigravida compared to primigravida were 78% vs 22% in group A, and 92% vs 8% in group B. Indication for C/S was previous C/S in 10 (20%) patients in group A, and 39 (78%) patients in group B, placenta previa, chorioamionitis, obstructed labour (6, 12% each); pregnancy induced hypertension and eclampsia in 5 (10%) cases in group A only. Intra-operative complications in group A were 48 (96%) vs 15 (30%) in group B (p = 0.000). Postoperative morbidity in group A was 50 (100%) and 26 (52%) in group B (p = 0.000). Intra-operative complication was haemorrhage in 46 (92%) cases in group A and 11 (22%) in group B. Anaesthetic complications were 40 (80%); prolonged intubation 25 (50%), aspiration of gastric contents 8 (16%), and difficult intubation 7 (14%) in group A. Ten (20%) cases had anaesthetic complications in group B. Commonest postoperative complication in both groups was anaemia in 41 (82%) and 11 (22%) cases respectively. CONCLUSION: Maternal morbidity is significantly higher in emergency C/S. Haemorrhage is a frequent complication in C/S, emergency or elective.