The prolonged survival of fibroblasts with forced lipid catabolism in visceral fat following encapsulation in alginate-poly-L-lysine

Although alginate-poly-L-lysine (AP(L)) encapsulation of cells producing bioactive peptides has been widely tested, it is unknown whether AP(L) supports lasting catabolic functions of encapsulated cells in adipose tissue, which are required for obesity reduction. We tested functions of AP(L)-encapsulated fibroblasts isolated from wild-type (WT) and aldehyde dehydrogenase 1a1 knockout mice (KO), which resist obesity on a high-fat (HF) diet, have a higher metabolic rate, and express increased levels of thermogenic uncoupling protein-1 (Ucp1) in their deleterious visceral fat depots compared to WT mice. To enable in vivo detection and quantification, fibroblasts were stably transfected with green-fluorescent protein. WT- or KO-containing microcapsules were injected into two visceral depots of WT mice fed an HF diet. Eighty days after transplantation, microcapsules were located in vivo using magnetic resonance imaging. KO microcapsules prevented weight gain in obese WT mice compared to a mock- and WT capsule-injected groups on an HF diet. The weight loss in KO-treated mice corresponded to lipid reduction and induction of thermogenesis in the injected visceral fat. The non-treated subcutaneous fat was not altered. Our data suggest that the AP(L) polymer supports long-term catabolic functions of genetically-modified fibroblasts, which can be potentially used for depot-specific obesity treatment.     

Differences in methylation patterns in the methylation boundary region of IDS gene in Hunter syndrome patients: implications for CpG hot spot mutations

Hunter syndrome, an X-linked disorder, results from deficiency of iduronate-2-sulfatase (IDS). Around 40% of independent point mutations at IDS were found at CpG sites as transitional events. The 15 CpG sites in the coding sequences of exons 1 and 2, which are normally hypomethylated, account for very few of transitional mutations. By contrast, the CpG sites in the coding sequences of exon 3, though also normally hypomethylated, account for much higher fraction of transitional mutations. To better understand relationship between methylation status and CpG transitional mutations in this region, the methylation patterns of 11 Hunter patients with transitional mutations at CpG sites were investigated using bisulfite genomic sequencing. The patient cohort mutation spectrum is composed of one mutation in exon 1 (one patient) and three different mutations in exon 3 (10 patients). We confirmed that in normal males, cytosines at the CpG sites from the promoter region to a portion of intron 3 were hypomethylated. However, specific CpG sites in this area were more highly methylated in patients. The patients with p.R8X (exon 1), p.P86L (exon 3), and p.R88H (exon 3) mutations had a hypermethylated condition in exon 2 to intron 3 but retained hypomethylation in exon 1. The same trend was found in four patients with p.A85T (exon 3), although the degree of hypermethylation was less. These findings suggest methylation patterns in the beginning of IDS genomic region are polymorphic in humans and that hypermethylation in this region in some individuals predisposes them to CpG mutations resulting in Hunter syndrome.     

A case report of solitary fibrous tumor of the pleura: ultrasound diagnostic features

Solitary fibrous tumor of the pleura is a rarely encountered clinical entity. Although the majority of these neoplasms have a benign course, the malignant form has also been reported. We describe the case of a 57-year-old male smoker with diabetes who was incidentally diagnosed on chest X-ray with a large solitary mass of the left hemithorax. The diagnostic tests included computed tomography, ultrasound, and contrast-enhanced ultrasound. Radical surgical resection was performed and histological examination confirmed a malignant solitary fibrous tumor of the pleura. The novelty of the case is the use of contrast-enhanced ultrasound in the diagnostic workup.     

Coatings Based on Phosphate Cements for Fire Protection of Steel Structures

Fire events in buildings can cause losses to human life and important material damage, therefore a great deal of attention is paid nowadays to fire prevention. Buildings based on steel structures are especially affected in the event of a fire, due to the important loss of load-bearing capability when steel is heated at temperatures higher than 500 °C. Therefore, one possible method to mitigate the deleterious effect of fire is to protect steel structures from direct heating by applying protective coatings. In this paper, the ability of magnesium phosphate cement (MPC), based on dead burned magnesite and calcium magnesium phosphate cement (CMPC) coatings, to protect a steel substrate was assessed. CMPCs were obtained by mixing partially calcined dolomite with a KH₂PO₄ (MKP) solution, and in some cases, with a setting retarder (borax). The main mineralogical compounds assessed by X-ray diffraction and electronic microscopy (SEM-EDS) in CMPC are MgO, CaCO₃, and K-struvite (KMgPO₄·6H₂O). The coatings based on MPC and CMPC, applied to steel plates, were tested in direct contact with a flame; the coatings of MPC and CMPC without the borax addition prevented the temperature increase of a metal substrate above 500 °C. No exfoliation of coatings (MPC and CMPC without borax addition) was noticed during the entire period of the test (45 min).     

Extracorporeal life support in cardiotoxicant poisoning—A narrative review

Extracorporeal life support (ECLS) improves circulation in life-threatening cardiac dysfunction or arrest patients. Its benefits in drug-induced cardiovascular complications are debated. Indications and outcomes are poorly established. We performed a narrative review discussing ECLS indications, timing and results in cardiotoxicant-poisoned patients. The review was focused on antiarrhythmic drugs and aluminium phosphide. Literature analysis was limited to the past 30 years in adults. Most reports were single cases and retrospective except one prospective case series of limited size, two of them controlled. ECLS indications and timing were at the discretion of physicians in charge but mostly included persistent cardiovascular failure despite elevated doses of inotropic/vasopressor support associated with elevated blood lactate concentrations (usually, >5 mmol/L) and collapsed left ventricular ejection fraction (LVEF; usually, ≤40%). Survival improved using ECLS versus standard care in one study. Survival was ~80% if ECLS was implemented in refractory cardiovascular failure and 25%–66% if implemented in cardiac arrest. In two controlled studies, survival of ECLS-treated aluminium phosphide-poisoned patients was improved versus standard care, if implemented in the presence of systolic blood pressure ≤80 mmHg despite inotropic/vasopressor treatment, arterial pH ≤ 7.0 and LVEF ≤ 40%. Despite low-to-moderate level of evidence, ECLS seems effective to improve survival in selected cardiotoxicant-poisoned patients. Selection criteria need clarification.