Commentary: Be selective when you wedge Linden, Philip A.
The Journal of thoracic and cardiovascular surgery,
October 2021, 2021-10-00, 20211001, Letnik:
162, Številka:
4
Journal Article
We examine the relationship between the general factor of personality (GFP) and emotional intelligence (EI) and specifically test the hypothesis that the GFP is a social effectiveness factor ...overlapping conceptually with EI. Presented is an extensive meta-analysis in which the associations between the GFP, extracted from the Big Five dimensions, with various EI measures is examined. Based on a total sample of k = 142 data sources (N = 36,268) the 2 major findings from the meta-analysis were (a) a large overlap between the GFP and trait EI (r ≈ .85); and (b) a positive, but more moderate, correlation with ability EI (r ≈ .28). These findings show that high-GFP individuals score higher on trait and ability EI, supporting the notion that the GFP is a social effectiveness factor. The findings also suggest that the GFP is very similar, perhaps even synonymous, to trait EI.
Key points
The gastrointestinal epithelial enterochromaffin (EC) cell synthesizes the vast majority of the body's serotonin. As a specialized mechanosensor, the EC cell releases this serotonin in ...response to mechanical forces. However, the molecular mechanism of EC cell mechanotransduction is unknown.
In the present study, we show, for the first time, that the mechanosensitive ion channel Piezo2 is specifically expressed by the human and mouse EC cells.
Activation of Piezo2 by mechanical forces results in a characteristic ionic current, the release of serotonin and stimulation of gastrointestinal secretion.
Piezo2 inhibition by drugs or molecular knockdown decreases mechanosensitive currents, serotonin release and downstream physiological effects.
The results of the present study suggest that the mechanosensitive ion channel Piezo2 is specifically expressed by the EC cells of the human and mouse small bowel and that it is important for EC cell mechanotransduction.
The enterochromaffin (EC) cell in the gastrointestinal (GI) epithelium is the source of nearly all systemic serotonin (5‐hydroxytryptamine; 5‐HT), which is an important neurotransmitter and endocrine, autocrine and paracrine hormone. The EC cell is a specialized mechanosensor, and it is well known that it releases 5‐HT in response to mechanical forces. However, the EC cell mechanotransduction mechanism is unknown. The present study aimed to determine whether Piezo2 is involved in EC cell mechanosensation. Piezo2 mRNA was expressed in human jejunum and mouse mucosa from all segments of the small bowel. Piezo2 immunoreactivity localized specifically within EC cells of human and mouse small bowel epithelium. The EC cell model released 5‐HT in response to stretch, and had Piezo2 mRNA and protein, as well as a mechanically‐sensitive inward non‐selective cation current characteristic of Piezo2. Both inward currents and 5‐HT release were inhibited by Piezo2 small interfering RNA and antagonists (Gd3+ and D‐GsMTx4). Jejunum mucosal pressure increased 5‐HT release and short‐circuit current via submucosal 5‐HT3 and 5‐HT4 receptors. Pressure‐induced secretion was inhibited by the mechanosensitive ion channel antagonists gadolinium, ruthenium red and D‐GsMTx4. We conclude that the EC cells in the human and mouse small bowel GI epithelium selectively express the mechanosensitive ion channel Piezo2, and also that activation of Piezo2 by force leads to inward currents, 5‐HT release and an increase in mucosal secretion. Therefore, Piezo2 is critical to EC cell mechanosensitivity and downstream physiological effects.
Key points
The gastrointestinal epithelial enterochromaffin (EC) cell synthesizes the vast majority of the body's serotonin. As a specialized mechanosensor, the EC cell releases this serotonin in response to mechanical forces. However, the molecular mechanism of EC cell mechanotransduction is unknown.
In the present study, we show, for the first time, that the mechanosensitive ion channel Piezo2 is specifically expressed by the human and mouse EC cells.
Activation of Piezo2 by mechanical forces results in a characteristic ionic current, the release of serotonin and stimulation of gastrointestinal secretion.
Piezo2 inhibition by drugs or molecular knockdown decreases mechanosensitive currents, serotonin release and downstream physiological effects.
The results of the present study suggest that the mechanosensitive ion channel Piezo2 is specifically expressed by the EC cells of the human and mouse small bowel and that it is important for EC cell mechanotransduction.
Itraconazole (ITZ) is a well-known antifungal agent that also has anticancer activity. In this study, we identify ITZ as a broad-spectrum inhibitor of enteroviruses (e.g., poliovirus, coxsackievirus, ...enterovirus-71, rhinovirus). We demonstrate that ITZ inhibits viral RNA replication by targeting oxysterol-binding protein (OSBP) and OSBP-related protein 4 (ORP4). Consistently, OSW-1, a specific OSBP/ORP4 antagonist, also inhibits enterovirus replication. Knockdown of OSBP inhibits virus replication, whereas overexpression of OSBP or ORP4 counteracts the antiviral effects of ITZ and OSW-1. ITZ binds OSBP and inhibits its function, i.e., shuttling of cholesterol and phosphatidylinositol-4-phosphate between membranes, thereby likely perturbing the virus-induced membrane alterations essential for viral replication organelle formation. ITZ also inhibits hepatitis C virus replication, which also relies on OSBP. Together, these data implicate OSBP/ORP4 as molecular targets of ITZ and point to an essential role of OSBP/ORP4-mediated lipid exchange in virus replication that can be targeted by antiviral drugs.
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•ITZ, an antifungal and anticancer agent, is a broad-spectrum enterovirus inhibitor•OSBP and ORP4 are identified as novel targets of ITZ•ITZ binds OSBP and inhibits OSBP-mediated lipid exchange at membrane contact sites•ITZ also inhibits hepatitis C virus replication
Strating et al. present the antifungal drug itraconazole as a novel inhibitor of a broad range of viruses, including poliovirus and hepatitis C virus. Itraconazole acted on a novel target, the oxysterol-binding protein (OSBP), a protein that has an essential role in lipid transfer.
Objectives CyberKnife stereotactic body radiosurgery is a potentially curative option for medically inoperable Stage I lung cancer. Fiducial marker placement in or near the tumor is required. ...Transthoracic placement using computed tomography guidance has been associated with a high risk of iatrogenic pneumothorax. Electromagnetic navigation bronchoscopy offers a safer method of placing markers; however, previous studies using linear markers have shown at least a 10% dislocation rate. We describe the use of coil-spring fiducial markers placed under moderate sedation in an outpatient bronchoscopy suite. Methods A total of 52 consecutive nonoperative patients with isolated lung tumors underwent fiducial placement using electromagnetic navigation bronchoscopy. Of the 52 patients, 4 received 17 linear fiducial markers, and 49 patients with 56 tumors received 217 coil-spring fiducial markers. The procedures were considered successful if the fiducial markers had been placed in or near the tumors and had remained in place without migration, allowing radiosurgery without the need for additional fiducial markers. Results A total of 234 fiducial markers were successfully deployed in 52 patients with 60 tumors (mean diameter 23.7 mm). Of these 60 tumors, 35 (58%) were adjacent to the pleura. At CyberKnife planning, 8 (47%) of 17 linear fiducial markers and 215 (99%) of 217 coil-spring fiducial markers ( P = .0001) were still in place. Of the 4 patients with linear fiducial markers, 2 required additional fiducial placements; none of the patients with coil fiducial markers required additional procedures. Three pneumothoraces (5.8%) occurred in peripheral lesions (2 were treated with a pig-tail chest tube and 1 with observation only). Conclusions Deployment of coil spring fiducial markers using navigation bronchoscopy can safely be performed with the patient under moderate sedation with almost no migration and a 5.8% rate of pneumothorax.
Anastomotic leaks after esophagectomy are a significant cause of postoperative morbidity and death. Barium esophagram and esophagogastroduodenoscopy are commonly used to survey for leaks; however, ...each has inherent risks and limitations. We sought to evaluate the effectiveness of daily drain amylase levels in detecting anastomotic leaks after esophagectomy.
We retrospectively reviewed 146 consecutive patients who underwent esophagectomy with cervical and intrathoracic anastomosis using gastric conduit. We collected daily drain amylase levels and obtained postoperative barium esophagrams routinely. Receiver operating characteristic analysis was performed to evaluate the ability of drain amylase to detect anastomotic leaks and to determine the sensitivity and specificity at various cutoff values.
There were no in-hospital or outpatient deaths within 30 days of operation in this consecutive series of patients. A leak occurred in 22 of 146 esophagectomy patients (15%) that required postoperative intervention. An additional 13 patients (9%) had a leak requiring only alteration of diet or antibiotics. The sensitivity and specificity for barium esophagram was 36.9% and 95%, respectively. For drain amylase obtained on postoperative day 4, a cutoff of 38 IU/L yielded a sensitivity of 100% and a specificity of 52.0%, and a cutoff of 250 IU/L yielded a sensitivity of 66.7% and a specificity of 95.9% in detecting leaks eventually requiring intervention.
Drain amylase levels recorded on day 4 after esophagectomy are more accurate for the detection of esophageal anastomotic leak than barium esophagram. Drain amylase levels represent a noninvasive test that may facilitate safe, early discharge after esophagectomy.
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