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Price along with associated factors associated with refusal to perform immunochemical Faecal Occult Blood vessels Test (iFOBT) amongst semi-urban areas.
These studies suggest that in barrier sites such as the intestinal tract, where pathogen-associated molecular patterns are abundant, cytosolic surveillance systems such as STING are well positioned to detect pathogenic bacteria.Lung-resident macrophages are crucial to the maintenance of health and in the defence against lower respiratory tract infections. Macrophages adapt to local environmental cues that drive their appropriate function; however, this is often dysregulated in many inflammatory lung pathologies. In mucosal tissues, neuro-immune interactions enable quick and efficient inflammatory responses to pathogenic threats. Although a number of factors that influence the antimicrobial response of lung macrophages are known, the role of neuronal factors is less well understood. Here, we show an intricate circuit involving the neurotrophic factor, neurturin (NRTN) on human lung macrophages that dampens pro-inflammatory cytokine release and modulates the type of matrix metalloproteinases produced in response to viral stimuli. #link# This circuit involves type 1 interferon-induced up-regulation of RET that when combined with the glial cell line-derived neurotrophic factor (GDNF) receptor α2 (GFRα2) allows binding to epithelial-derived NRTN. Our research highlights a non-neuronal immunomodulatory role for NRTN and a novel process leading to a specific antimicrobial immune response by human lung-resident macrophages.
The enteric nervous system (ENS) plays a key role in controlling the gut-brain axis under normal and pathological conditions, such as type 2 diabetes. The discovery of intestinal actors, such as enterosynes, able to modulate the ENS-induced duodenal contraction is considered an innovative approach. Among all the intestinal factors, the understanding of the role of gut microbes in controlling glycaemia is still developed. We studied whether the modulation of gut microbiota by prebiotics could permit the identification of novel enterosynes.

We measured the effects of prebiotics on the production of bioactive lipids in the intestine and tested the identified lipid on ENS-induced contraction and glucose metabolism. Then, we studied the signalling pathways involved and compared the results obtained in mice to human.

We found that modulating the gut microbiota with prebiotics modifies the actions of enteric neurons, thereby controlling duodenal contraction and subsequently attenuating hyperglycaemia in diabetic mice. link2 We discovered that the signalling pathway involved in these effects depends on the synthesis of a bioactive lipid 12-hydroxyeicosatetraenoic acid (12-HETE) and the presence of mu-opioid receptors (MOR) on enteric neurons. Using pharmacological approaches, we demonstrated the key role of the MOR receptors and proliferator-activated receptor γ for the effects of 12-HETE. These findings are supported by human data showing a decreased expression of the proenkephalin and MOR messanger RNAs in the duodenum of patients with diabetic.

Using a prebiotic approach, we identified enkephalin and 12-HETE as new enterosynes with potential real beneficial and safety impact in diabetic human.
Using a prebiotic approach, we identified enkephalin and 12-HETE as new enterosynes with potential real beneficial and safety impact in diabetic human.
Blebs are important secondary structures of intracranial aneurysms associated with increased rupture risk and can affect local wall stress and hemodynamics. Mechanisms of bleb development and evolution are not clearly understood. We investigate the relationship between blebs with different wall characteristics and local hemodynamics and rupture sites.

Blebs with different wall appearances in intra-operative videos were analyzed with image-based computational fluid dynamics. Thin red blebs were compared against thick atherosclerotic/hyperplastic white/yellow blebs. Rupture points were identified in videos of ruptured aneurysms harboring blebs.

Thin blebs tended to be closer to the inflow than atherosclerotic blebs of the same aneurysm (P=0.0234). Blebs near the inflow had higher velocity (P=0.0213), vorticity (P=0.0057), shear strain rate (P=0.0084), wall shear stress (WSS) (P=0.0085), and WSS gradient (P=0.0151) than blebs far from the inflow. In a subset of 12 ruptured aneurysms harboring blebs, rupturthin blebs, atherosclerotic blebs, and even away from blebs. Further study of wall failure in aneurysms with different bleb types is needed.
To investigate in situ decellularization of a large animal model of saccular aneurysm as a strategy for achieving aneurysmal growth and lasting inflammation.

18 New Zealand White rabbits were randomized 21 to receive endoluminal sodium dodecyl sulfate infusion (SDS, 1% solution, 45 min) following elastase or elastase-only treatment (control). All aneurysms were measured by digital subtraction angiography every 2 weeks. Every 2 weeks, three of the rabbits (two elastase + SDS, one control) underwent MRI, followed by contrast injection with myeloperoxidase (MPO)-sensing contrast agent. MRI was repeated 3 hours after contrast injection and the enhancement ratio (ER) was calculated. Following MRI, aneurysms were explanted and subjected to immunohistopathology.

During follow-up MRI, the average ER for SDS-treated animals was 1.63±0.20, compared with 1.01±0.06 for controls (p<0.001). The width of SDS-treated aneurysms increased significantly in comparison with the elastase aneurysms (47% vs 20%, p<0.001). Image analysis of thin sections showed infiltration of MPO-positive cells in decellularized aneurysms and surroundings through the 12-week observation period while control tissue had 5-6 times fewer cells present 2 weeks after aneurysm creation. Immunohistochemistry demonstrated the presence of MPO-positive cells surrounding decellularized lesions at early time points. MPO-positive cells were found in the adventitia and in the thrombi adherent to the aneurysm wall at later time points.

In situ decellularization of a large animal model of saccular aneurysms reproduces features of unstable aneurysms, such as chronic inflammation (up to 12 weeks) and active aneurysm wall remodeling, leading to continued growth over 8 weeks.
In situ decellularization of a large animal model of saccular aneurysms reproduces features of unstable aneurysms, such as chronic inflammation (up to 12 weeks) and active aneurysm wall remodeling, leading to continued growth over 8 weeks.Histone H3 lysine 36 methylation (H3K36me) is a conserved histone modification associated with transcription and DNA repair. Although the effects of H3K36 methylation have been studied, the genome-wide dynamics of H3K36me deposition and removal are not known. link3 We established rapid and reversible optogenetic control for Set2, the sole H3K36 methyltransferase in yeast, by fusing the enzyme with the light-activated nuclear shuttle (LANS) domain. Light activation resulted in efficient Set2-LANS nuclear localization followed by H3K36me3 deposition in vivo, with total H3K36me3 levels correlating with RNA abundance. Although genes showed disparate levels of H3K36 methylation, relative rates of H3K36me3 accumulation were largely linear and consistent across genes, suggesting that H3K36me3 deposition occurs in a directed fashion on all transcribed genes regardless of their overall transcription frequency. Removal of H3K36me3 was highly dependent on the demethylase Rph1. However, the per-gene rate of H3K36me3 loss weakly correlated with RNA abundance and followed exponential decay, suggesting H3K36 demethylases act in a global, stochastic manner. Altogether, these data provide a detailed temporal view of H3K36 methylation and demethylation that suggests transcription-dependent and -independent mechanisms for H3K36me deposition and removal, respectively.The SARS-CoV-2 (COVID-19) pandemic has significantly impacted the management of patients with gynecologic cancers. Many centers have reduced access to routine visits to avoid crowded waiting areas and specially to reduce the infection risk for oncologic patients. The goal of this review is to propose a surveillance algorithm for patients with gynecologic cancers during the COVID-19 pandemic based on existing evidence and established guidelines. It is time to consider strategies based on telemedicine and to adapt protocols in this new era. We hereby propose a strategy for routine surveillance both during and beyond the pandemic.
Overexpression of the epidermal growth factor receptor (EGFR) found in common subtypes of endometrial cancer has been associated with advanced stage disease and a poor prognosis. The purpose of this phase 2 study was to evaluate the efficacy and safety of cetuximab in patients with recurrent endometrial cancer.

The study was an open-label phase 2 clinical trial conducted at two institutions. Patients with recurrent or progressive endometrial cancer of any histologic type with the exception of uterine sarcoma received cetuximab at an initial dose of 400 mg/m
IV followed by weekly doses of 250 mg/m
. One cycle was considered 4 weeks of treatment. The primary efficacy endpoint was clinical benefit response, defined as a complete or partial response or prolonged stable disease (>8 weeks) by RECIST 1.0 criteria.

A total of 30 patients were enrolled with a median age of 64 years (range 42-83). Of the 20 evaluable patients, three (15%) had clinical benefit response (one complete response, two stable disease). The patient with a clinical benefit response received a total of 27 cycles and the two patients with stable disease were taken off the study due to progression after four and six cycles, respectively. Of click here , nine received ≤1 cycle due to clinical deterioration and one had an anaphylactic reaction. One patient had a grade 3 rash which resolved after a delay in treatment. No dose reduction was reported.

In this cohort, single agent therapy with cetuximab was well tolerated and had a 15% clinical benefit response. Further studies are required to better identify patients who may respond to this treatment.
In this cohort, single agent therapy with cetuximab was well tolerated and had a 15% clinical benefit response. Further studies are required to better identify patients who may respond to this treatment.The lysyl hydroxylases (procollagen-lysine 5-dioxygenases) PLOD1, PLOD2, and PLOD3 have been proposed as pathogenic mediators of stunted lung development in bronchopulmonary dysplasia (BPD), a common complication of preterm birth. In affected infants, pulmonary oxygen toxicity stunts lung development. Mice lacking Plod1 exhibit 15% mortality, and mice lacking Plod2 or Plod3 exhibit embryonic lethality. Therefore, to address any pathogenic role of lysyl hydroxylases in stunted lung development associated with BPD, minoxidil was administered to newborn mice in an oxygen toxicity-based BPD animal model. Minoxidil, which has attracted much interest in the management of systemic hypertension and androgenetic alopecia, can also be used to reduce lysyl hydroxylase activity in cultured cells. An in vivo pilot dosing study established 50 mg⋅kg-1⋅day-1 as the maximum possible minoxidil dose for intraperitoneal administration in newborn mouse pups. When administered at 50 mg⋅kg-1⋅day-1 to newborn mouse pups, minoxidil was detected in the lungs but did not impact lysine hydroxylation, collagen crosslinking, or lysyl hydroxylase expression in the lungs.
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