On the Lie ring of derivations of a semiprime ring

We prove that the Lie ring of derivations of a semiprime ring is either trivial or non-nilpotent

Cpd-1 Null Mice Display a Subtle Neurological Phenotype

CPD1 (also known as ANP32-E) belongs to a family of evolutionarily conserved acidic proteins with leucine rich repeats implicated in a variety of cellular processes regulating gene expression, vesicular trafficking, intracellular signaling and apoptosis. Because of its spatiotemporal expression pattern, CPD1 has been proposed to play an important role in brain morphogenesis and synaptic development.We have generated CPD1 knock-out mice that we have subsequently characterized. These mice are viable and fertile. However, they display a subtle neurological clasping phenotype and mild motor deficits.CPD1 is not essential for normal development; however, it appears to play a role in the regulation of fine motor functions. The minimal phenotype suggests compensatory biological mechanisms

IFSO (International Federation for Surgery of Obesity and Metabolic Disorders) Consensus Conference Statement on One-Anastomosis Gastric Bypass (OAGB-MGB): Results of a Modified Delphi Study

Background: One-anastomosis gastric bypass (OAGB-MGB) is currently the third performed primary bariatric surgical procedure worldwide. However, the procedure is hampered by numerous controversies and there is considerable variability in surgical technique, patient selection, and pre- and postoperative care among the surgeons performing this procedure. This paper reports the results of a modified Delphi consensus study organized by the International Federation for Surgery of Obesity and Metabolic Disorders (IFSO). Methods: Fifty-two internationally recognized bariatric experts from 28 countries convened for voting on 90 consensus statements over two rounds to identify those on which consensus could be reached. Inter-voter agreement of ≥ 70% was considered consensus, with voting participation ≥ 80% considered a robust vote. Results: At least 70% consensus was achieved for 65 of the 90 questions (72.2% of the items), 61 during the first round of voting and an additional four in the second round. Where consensus was reached on a binary agree/disagree or yes/no item, there was agreement with the statement presented in 53 of 56 instances (94.6%). Where consensus was reached on a statement where options favorable versus unfavorable to OAGB-MGB were provided, including statements in which OAGB-MGB was compared to another procedure, the response option favorable to OAGB-MGB was selected in 13 of 23 instances (56.5%). Conclusion: Although there is general agreement that the OAGB-MGB is an effective and usually safe option for the management of patients with obesity or severe obesity, numerous areas of non-consensus remain in its use. Further empirical data are needed

NOV/CCN3 attenuates inflammatory pain through regulation of matrix metalloproteinases-2 and -9

<p>Abstract</p> <p>Background</p> <p>Sustained neuroinflammation strongly contributes to the pathogenesis of pain. The clinical challenge of chronic pain relief led to the identification of molecules such as cytokines, chemokines and more recently matrix metalloproteinases (MMPs) as putative therapeutic targets. Evidence points to a founder member of the matricial CCN family, NOV/CCN3, as a modulator of these inflammatory mediators. We thus investigated the possible involvement of NOV in a preclinical model of persistent inflammatory pain.</p> <p>Methods</p> <p>We used the complete Freund's adjuvant (CFA)-induced model of persistent inflammatory pain and cultured primary sensory neurons for <it>in vitro </it>experiments. The mRNA expression of NOV and pro-inflammatory factors were measured with real-time quantitative PCR, CCL2 protein expression was assessed using ELISA, MMP-2 and -9 activities using zymography. The effect of drugs on tactile allodynia was evaluated by the von Frey test.</p> <p>Results</p> <p>NOV was expressed in neurons of both dorsal root ganglia (DRG) and dorsal horn of the spinal cord (DHSC). After intraplantar CFA injection, NOV levels were transiently and persistently down-regulated in the DRG and DHSC, respectively, occurring at the maintenance phase of pain (15 days). NOV-reduced expression was restored after treatment of CFA rats with dexamethasone. <it>In vitro</it>, results based on cultured DRG neurons showed that siRNA-mediated inhibition of NOV enhanced IL-1β- and TNF-α-induced MMP-2, MMP-9 and CCL2 expression whereas NOV addition inhibited TNF-α-induced MMP-9 expression through β₁integrin engagement. <it>In vivo</it>, the intrathecal delivery of MMP-9 inhibitor attenuated mechanical allodynia of CFA rats. Importantly, intrathecal administration of NOV siRNA specifically led to an up-regulation of MMP-9 in the DRG and MMP-2 in the DHSC concomitant with increased mechanical allodynia. Finally, NOV intrathecal treatment specifically abolished the induction of MMP-9 in the DRG and, MMP-9 and MMP-2 in the DHSC of CFA rats. This inhibitory effect on MMP is associated with reduced mechanical allodynia.</p> <p>Conclusions</p> <p>This study identifies NOV as a new actor against inflammatory pain through regulation of MMPs thus uncovering NOV as an attractive candidate for therapeutic improvement in pain relief.</p

Patient Selection in One Anastomosis/Mini Gastric Bypass—an Expert Modified Delphi Consensus

Purpose: One anastomosis/mini gastric bypass (OAGB/MGB) is up to date the third most performed obesity and metabolic procedure worldwide, which recently has been endorsed by ASMBS. The main criticisms are the risk of bile reflux, esophageal cancer, and malnutrition. Although IFSO has recognized this procedure, guidance is needed regarding selection criteria. To give clinicians a daily support in performing the right patient selection in OAGB/MGB, the aim of this paper is to generate clinical guidelines based on an expert modified Delphi consensus. Methods: A committee of 57 recognized bariatric surgeons from 24 countries created 69 statements. Modified Delphi consensus voting was performed in two rounds. An agreement/disagreement among ≥ 70.0% of the experts was considered to indicate a consensus. Results: Consensus was achieved for 56 statements. Remarkably, ≥ 90.0% of the experts felt that OAGB/MGB is an acceptable and suitable option "in patients with Body mass index (BMI) > 70, BMI > 60, BMI > 50 kg/m2 as a one-stage procedure," "as the second stage of a two-stage bariatric surgery after Sleeve Gastrectomy for BMI > 50 kg/m2 (instead of BPD/DS)," and "in patients with weight regain after restrictive procedures. No consensus was reached on the statement that OAGB/MGB is a suitable option in case of resistant Helicobacter pylori. This is likely as there is a concern that this procedure is associated with reflux and its related long-term complications including risk of cancer in the esophagus or stomach. Also no consensus reached on OAGB/MGB as conversional surgery in patients with GERD after restrictive procedures. Consensus for disagreement was predominantly achieved "in case of intestinal metaplasia of the stomach" (74.55%), "in patients with severe Gastro Esophageal Reflux Disease (GERD)(C,D)" (75.44%), "in patients with Barrett's metaplasia" (89.29%), and "in documented insulinoma" (89.47%). Conclusion: Patient selection in OAGB/MGB is still a point of discussion among experts. There was consensus that OAGB/MGB is a suitable option in elderly patients, patients with low BMI (30-35 kg/m2) with associated metabolic problems, and patients with BMIs more than 50 kg/m2 as one-stage procedure. OAGB/MGB can also be a safe procedure in vegetarian and vegan patients. Although OAGB/MGB can be a suitable procedure in patients with large hiatal hernia with concurrent hiatal hernia, it should not be offered to patients with grade C or D esophagitis or Barrett's metaplasia.info:eu-repo/semantics/publishedVersio

Defining the Earliest Transcriptional Steps of Chondrogenic Progenitor Specification during the Formation of the Digits in the Embryonic Limb

The characterization of genes involved in the formation of cartilage is of key importance to improve cell-based cartilage regenerative therapies. Here, we have developed a suitable experimental model to identify precocious chondrogenic events in vivo by inducing an ectopic digit in the developing embryo. In this model, only 12 hr after the implantation of a Tgfβ bead, in the absence of increased cell proliferation, cartilage forms in undifferentiated interdigital mesoderm and in the course of development, becomes a structurally and morphologically normal digit. Systematic quantitative PCR expression analysis, together with other experimental approaches allowed us to establish 3 successive periods preceding the formation of cartilage. The “pre-condensation stage”, occurring within the first 3 hr of treatment, is characterized by the activation of connective tissue identity transcriptional factors (such as Sox9 and Scleraxis) and secreted factors (such as Activin A and the matricellular proteins CCN-1 and CCN-2) and the downregulation of the galectin CG-8. Next, the “condensation stage” is characterized by intense activation of Smad 1/5/8 BMP-signaling and increased expression of extracellular matrix components. During this period, the CCN matricellular proteins promote the expression of extracellular matrix and cell adhesion components. The third period, designated the “pre-cartilage period”, precedes the formation of molecularly identifiable cartilage by 2–3 hr and is characterized by the intensification of Sox 9 gene expression, along with the stimulation of other pro-chondrogenic transcription factors, such as HifIa. In summary, this work establishes a temporal hierarchy in the regulation of pro-chondrogenic genes preceding cartilage differentiation and provides new insights into the relative roles of secreted factors and cytoskeletal regulators that direct the first steps of this process in vivo

Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK

Background Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting.Methods 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey.Results 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD.Conclusion We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting