Role of sialidase Neu3 and ganglioside GM3 in cardiac fibroblasts activation.

Cardiac fibrosis is a key physiological response to cardiac tissue injury to protect the heart from wall rupture. However, its progression increases heart stiffness, eventually causing a decrease in heart contractility. Unfortunately, to date, no efficient antifibrotic therapies are available to the clinic. This is primarily due to the complexity of the process, which involves several cell types and signaling pathways. For instance, the transforming growth factor beta (TGF-β) signaling pathway has been recognized to be vital for myofibroblasts activation and fibrosis progression. In this context, complex sphingolipids, such as ganglioside GM3, have been shown to be directly involved in TGF-β receptor 1 (TGF-R1) activation. In this work, we report that an induced up-regulation of sialidase Neu3, a glycohydrolytic enzyme involved in ganglioside cell homeostasis, can significantly reduce cardiac fibrosis in primary cultures of human cardiac fibroblasts by inhibiting the TGF-β signaling pathway, ultimately decreasing collagen I deposition. These results support the notion that modulating ganglioside GM3 cell content could represent a novel therapeutic approach for cardiac fibrosis, warranting for further investigations

Case report: Complex arterial findings in vascular ehlers-danlos syndrome with a novel COL3A1 variant and death at young age

Vascular Ehlers-Danlos syndrome (vEDS) is a genetic disease caused by a pathogenic mutation in the COL3A1 gene. Despite its severe course, the rarity and extreme clinical variability of the disease can pose significant obstacles to a timely diagnosis. Early and accurate diagnosis may lead to improved patient outcomes by providing access to targeted pharmacological treatments like celiprolol and enhancing the management of vEDS-related complications. Herein, we report a patient harboring a novel de novo COL3A1 missense variant, in which the diagnosis was only possible belatedly due to delayed referral for genetic evaluation. The patient developed pulmonary complications, aneurysms, and vascular malformations, and died at the age of 26 years due to massive pulmonary bleeding

SCN5A Nonsense Mutation and NF1 Frameshift Mutation in a Family With Brugada Syndrome and Neurofibromatosis

In this case series, we report for the first time a family in which the inherited nonsense mutation [c. 3946C > T (p.Arg1316*)] in the SCN5A gene segregates in association with Brugada syndrome (BrS). Moreover, we also report, for the first time, the frameshift mutation [c.7686delG (p.Ile2563fsX40)] in the NF1 gene, as well as its association with type 1 neurofibromatosis (NF1), characterized by pigmentary lesions (café au lait spots, Lisch nodules, freckling) and cutaneous neurofibromas. Both of these mutations and associated phenotypes were discovered in the same family. This genetic association may identify a subset of patients at higher risk of sudden cardiac death who require the appropriate electrophysiological evaluation. This case series highlights the importance of genetic testing not only to molecularly confirm the pathology but also to identify asymptomatic family members who need clinical examinations and preventive interventions, as well as to advise about the possibility of avoiding recurrence risk with medically assisted reproduction

The Supreme Laryngeal Mask Airway\u2122 (LMA): a new neonatal supraglottic device: comparison with Classic and ProSeal LMA in a manikin.

none6noAim: The study aims to compare the performances (ease of insertion, time to establish effective ventilation and maximal inflation pressure) of classic™ (cLMA), ProSeal™ (PLMA) and Supreme™ (SLMA) Laryngeal Mask Airway when used in a neonatal airway management manikin by inexperienced delivery room trainees. The quality of the three devices, as perceived by participants, was also evaluated. Methods: Health-care professional trainees were given a brief supervised training with the three devices. Every trainee was then observed positioning each of the three different LMAs in a single occasion. Success rate, time (IT) and maximal inflation pressure (PI max) were recorded by a single unblinded observer. A 4-point scale was used to rate participants' perceived quality. Results: A total of 40 health-care professional trainees participated in the study.There were five, three and one failed insertions at the first attempt with the cLMA, PLMA and SLMA, respectively. No failures to establish an effective airway within three attempts were recorded. The success rate at first attempt was comparable among the three devices. The mean IT was significantly lower with the SLMA as compared with PLMA (p<0.01), but not to cLMA. The mean PI max was higher with SLMA than with cLMA and PLMA (p<0.01). The ease of insertion as well as the effectiveness of ventilation were perceived by the participants as superior with SLMA as compared with cLMA and PLMA (p<0.01). Conclusions: Neonatal SLMA is superior to PLMA in terms of time to establish effective ventilation; furthermore, maximal inflation pressure and quality perceived by the operator are higher with neonatal SLMA than with cLMA and PLMA. These manikin data could provide a useful guide for planning potential future clinical research involving the newly developed supraglottic device in neonates. © 2011 Elsevier Ireland Ltd.noneTrevisanuto D.; Parotto M.; Doglioni N.; Ori C.; Zanardo V.; Micaglio M.Trevisanuto, D.; Parotto, M.; Doglioni, N.; Ori, C.; Zanardo, V.; Micaglio, M

Maternal Oxygen Administration during Labor: A Controversial Practice

Oxygen administration to the mother is commonly performed during labor, especially in the case of a non-reassuring fetal heart rate, aiming to increase oxygen diffusion through the placenta to fetal tissues. The benefits and potential risks are controversial, especially when the mother is not hypoxemic. Its impact on placental gas exchange and the fetal acid–base equilibrium is not fully understood and it probably affects the sensible placental oxygen equilibrium causing a time-dependent vasoconstriction of umbilical and placental vessels. Hyperoxia might also cause the generation of radical oxygen species, raising concerns for the developing fetal cells. Moreover, this practice affects the maternal cardiovascular system, causing alterations of the cardiac index, heart rate and vascular resistance, and unclear effects on uterine blood flow. In conclusion, there is no evidence that maternal oxygen administration can provide any benefit in the case of a non-reassuring fetal heart rate pattern, while possible collateral effects warn of its utilization. Oxygen administration during labor should be reserved for cases of maternal hypoxia

Tracheal Intubation with Aura-i and aScope-2: How to Minimize Apnea Time in an Unpredicted Difficult Airway

The supraglottic airway’s usefulness as a dedicated airway is the subject of continuing development. We report the case of an obese patient with unpredicted difficult airway management in which a new “continuous ventilation technique” was used with the Aura-i laryngeal mask and the aScope-2 devices. The aScope-2/Aura-i system implemented airway devices for the management of predictable/unpredictable difficult airway. The original technique required the disconnection of the mount catheter from Aura-i, the introduction of the aScope-2 into the laryngeal mask used as a conduit for video assisted intubation and then towards the trachea, followed by a railroading of the tracheal tube over the aScope-2. This variation in the technique guarantees mechanical ventilation during the entire procedure and could prevent the risk of hypoventilation and/or hypoxia