Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro

The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated dense single-cell and spatial reference maps of the human uterus and three-dimensional endometrial organoid cultures. We dissect the signaling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids reveals the pathways and cell states regulating differentiation of the secretory and ciliated lineages both in vivo and in vitro. In vitro downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. We utilize our cellular maps to deconvolute bulk data from endometrial cancers and endometriotic lesions, illuminating the cell types dominating in each of these disorders. These mechanistic insights provide a platform for future development of treatments for common conditions including endometriosis and endometrial carcinoma.

Therapeutic dilemma and clinical issues in management of the button battery ingestion: a case report and literature review

The incidence of button battery ingestion in children less than 6 years, from year 1985 to 2019 was 59,000 and it is still a clinical challenge for pediatricians. Objects which are commonly ingested are large amounts of food, coins, toy parts, jewels, batteries, sharp materials and non-metallic sharp objects. It is an increased incidence of mortality and morbidity due to button battery ingestion, compared to accidental ingestion of other objects, due to its small size, and because of its potent source of energy. A literature search was carried out to evaluate the challenges in diagnosing, treatment, and follow-up of button battery ingested cases in children. A total of 36 original articles were included for the review.Conclusions: Button batteries can quickly cause severe damage to the mucosal lining of the GI tract. Esophageal button batteries require emergency removal because they can cause serious complications leading to hemorrhage, and death. In children, where the button battery has passed the esophagus watchful management should be made. In the majority of cases, the button batteries with a diameter less than 2 cm lodged in the stomach will pass spontaneously with no complications. However, asymptomatic children may be followed up with X-rays to assess progression up to 10–14 days after ingestion. Endoscopic or surgical removal may be required to prevent intestinal perforation with peritonitis. Symptomatic children will always need a consultation with a pediatric surgeon for surgery no matter where the button battery is placed in the GI tract. Developing countries shall adopt surveillance and reporting systems for BBI ingestion and related complications and it is recommended as essential to have management protocols in place for button batteries ingestion.

Nasolabial Flap and Simultaneous Cartilage Graft for Nasal Alar Reconstruction- A Case Report

A case of full thickness defect involving left ala of nose reconstructed with nasolabial flap for the coverage of skin and mucosal lining, along with simultaneous insertion of septal cartilage, which completes the reconstruction. Bangladesh J Otorhinolaryngol 2021; 27(2): 184-187

Colon Innervating TRPA1 Positive Nociceptors Influence Mucosal Health In Mice

Introduction: Transient receptor potential ankyrin-1 positive (TRPA1+ve) nociceptors, primarily present as peptidergic neuronal afferents in the colon are sensors of disturbance in lower gastrointestinal tract including pain induced by different pathologies. Their therapeutic role in the alleviation of chronic pain (receptor antagonism and receptor desensitization) associated with inflammatory bowel diseases (IBD) is reported. However, there is limited literature available about their role in formation and sustenance of the mucosal layer, and its interaction with host physiology as well as luminal microbial community. The aim of this study focuses on the effects of nociceptive TRPA1 channel desensitization on colonic mucus production and gut health. Methods: TRPA1+ve nociceptors were desensitized by rectal administration of capsazepine. Ileum, colon was harvested and cecum content was collected. We performed morphological/histological analysis, gut permeability alteration, gene expression changes, colon metabolite profiling, and gut microbial abundance in these animals. Results: We found that presence of TRPA1-positive nociceptors is required for mucus layer integrity, using an intra-rectal capsazepine-induced TRPA1 desensitization model. Desensitization of TRPA1 positive nociceptors resulted in damaged mucosal lining, resultant increase in gut permeability and altered transcriptional profile of genes for goblet cell markers, mucus regulation, immune response and tight junction proteins. The damage to mucosal lining prevented its role in enterosyne (short chain fatty acids) actions. Conclusion: These results suggest that caution may need to be exercised before employing TRPA1 desensitization as a therapeutic option to alleviate pain caused due to IBD.

Our Experience with Inverted Papilloma: about 61 Patients

Introduction: Inverted papilloma (IP) is the most common type of Schneiderian papilloma originating from the mucosal lining of the nose and paranasal cavities. It is a semi benign tumor with a high tendency for recurrences and malignant transformation. Management consists of a complete tumoral resection. Objective: to analyze surgical results considering the techniques (open or endoscopic surgery), the rate and time of recurrence. Method: We present herein a cohort of 61 patients treated in the CHU-UCL Godinne between 1998 and 2019. We analyzed the demographic data, the origin of the tumor, the staging, the surgical approach and the outcomes. The patients were classified into two groups: the first one includes 48 patients operated de novo in CHU-UCL Godinne and the second group 13 patients referred to us for revision surgery. Results: We observed 8 recurrences, all groups confounded. The global success rate was 87%. The number of recurrences in the first group was 6 out of 48 and 2 out of 13 in the second group. Following these results we propose an algorithm of treatment depending on the site of attachment of the IP. Conclusion: We confirmed that more extended surgeries such as Caldwell Luc procedure, medial maxillectomy, Draf IIb/III frontal sinusotomy or type III sphenoidotomy give better outcomes than more “limited” and functional surgeries such as Draf I/IIa frontal sinusotomy or middle antrostomy. The latter should be done only for specific and limited extension of the IP in the maxillary sinus. A subperiosteal dissection is mandatory in all cases. Keywords: inverted papilloma; retrospective study; surgery; recurrence

Cecal epidermoid cyst: a neonatal case with clinicopathological consideration

Background Only 10 cases of cecal epidermoid cyst (CEC) have been reported in the literature. Furthermore, its pathogenesis remains unclear. We report a rare case of congenital CEC in neonate, and discuss its clinicopathological findings. Case presentation A cystic lesion was incidentally identified in the retroperitoneal area of the abdominal right lower quadrant during a routine prenatal ultrasonography (US), prompting an ileocolectomy 3 days after birth. This congenital cyst was composed of mucosal lining cells and submucosal connective tissues, and the inner lining mucosa was composed of stratified squamous epithelium and focally mucin-producing ciliated epithelium. Based on the macroscopic and microscopic findings, the cystic lesion was diagnosed as a congenital cecal epidermoid cyst. Conclusions The management of a fetal abdominal mass should be tailored individually, considering that epidermoid cysts can occur in the cecum during the perinatal period. We report the clinicopathological findings in this case, including its possible pathogenesis.

Anti-Ulcer Activities of Methanolic Extract of Musa Paradisiaca

Musa paradisiaca (plantain peel) is useful in prevention and control of numerous health problems in Ayurveda, an ancient system of medicine. The anti-ulcer activity and effects of varied dosages of its methanolic extract on gastrointestinal motility were investigated in this study. Fifteen (15) Wistar rats of 150 and 200 g were deprived of food for 24 hours; then divided into five groups (Groups I through V) of three rats each; while group I (control) received 5ml/kg of distilled water, groups II, III and IV received 100 mg/kg of indomethacin (ulceric), 5mg/kg of omeprazole (after inducing ulcer), and 200 mg/kg of M. paradisiaca respectively. After inducing ulcers with indomethacin, Group V animals were fed (orally) with 400mg/kg of extract. Oral administration of ethanol injured the mucosal lining, resulting in gastrointestinal bleeding with ulcer indexes of 13.30, 10.57, 10.62, and 9.01 in groups II to V respectively, after some time of administration of test substances. In addition, the test statistic (using ANOVA and Tukey post-hoc) on the Omeprazole and 400mg/kg extract treated groups showed a substantial protection of 8.60% and 21.27 % respectively; whereas, the Omeprazole and 400mg/kg extract treated groups had a substantial protection of 8.60% and 21.27%, respectively. Between the omeprazole, 200mg/kg and 400mg/kg of extract treated groups, there was a statistically insignificant increase (p 0.05) in gastro-protective activity. However, gastro-protective effect was statistically significant (p 0.05) at larger doses of the extract. The ulcer index decreased significantly (p 0.05) between the negative control and treatment groups, according to the findings. However, with 400mg/kg body weight of the extract, the percentage gastro-protective action was higher than in the omeprazole-treated group. We advocate using a similar extract on other platforms to back up this study's efforts.

Maternal natural killer cells at the intersection between reproduction and mucosal immunity

Many maternal immune cells populate the decidua, which is the mucosal lining of the uterus transformed during pregnancy. Here, abundant natural killer (NK) cells and macrophages help the uterine vasculature adapt to fetal demands for gas and nutrients, thereby supporting fetal growth. Fetal trophoblast cells budding off the forming placenta and invading deep into maternal tissues come into contact with these and other immune cells. Besides their homeostatic functions, decidual NK cells can respond to pathogens during infection, but in doing so, they may become conflicted between destroying the invader and sustaining fetoplacental growth. We review how maternal NK cells balance their double duty both in the local microenvironment of the uterus and systemically, during toxoplasmosis, influenza, cytomegalovirus, malaria and other infections that threat pregnancy. We also discuss recent developments in the understanding of NK-cell responses to SARS-Cov-2 infection and the possible dangers of COVID-19 during pregnancy.

Hereditary Haemorrhagic Telangiectasia, an Inherited Vascular Disorder in Need of Improved Evidence-Based Pharmaceutical Interventions

Hereditary haemorrhagic telangiectasia (HHT) is characterised by arteriovenous malformations (AVMs). These vascular abnormalities form when arteries and veins directly connect, bypassing the local capillary system. Large AVMs may occur in the lungs, liver and brain, increasing the risk of morbidity and mortality. Smaller AVMs, known as telangiectases, are prevalent on the skin and mucosal lining of the nose, mouth and gastrointestinal tract and are prone to haemorrhage. HHT is primarily associated with a reduction in endoglin (ENG) or ACVRL1 activity due to loss-of-function mutations. ENG and ACVRL1 transmembrane receptors are expressed on endothelial cells (ECs) and bind to circulating ligands BMP9 and BMP10 with high affinity. Ligand binding to the receptor complex leads to activation of the SMAD1/5/8 signalling pathway to regulate downstream gene expression. Various genetic animal models demonstrate that disruption of this pathway in ECs results in AVMs. The vascular abnormalities underlying AVM formation result from abnormal EC responses to angiogenic and haemodynamic cues, and include increased proliferation, reduced migration against the direction of blood flow and an increased EC footprint. There is growing evidence that targeting VEGF signalling has beneficial outcomes in HHT patients and in animal models of this disease. The anti-VEGF inhibitor bevacizumab reduces epistaxis and has a normalising effect on high cardiac output in HHT patients with hepatic AVMs. Blocking VEGF signalling also reduces vascular malformations in mouse models of HHT1 and HHT2. However, VEGF signalling is complex and drives numerous downstream pathways, and it is not yet clear which pathway (or combination of pathways) is critical to target. This review will consider the recent evidence gained from HHT clinical and preclinical studies that are increasing our understanding of HHT pathobiology and informing therapeutic strategies.

Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro

The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated single-cell and spatial reference maps of the human uterus and 3D endometrial organoid cultures. We dissect the signalling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids highlights common pathways regulating the differentiation of secretory and ciliated lineage in vivo and in vitro. We show in vitro that downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. These mechanistic insights provide a platform for future development of treatments for a range of common endometrial disorders including endometriosis and carcinoma.