β1‐receptor polymorphisms and junctional ectopic tachycardia in children after cardiac surgery

Junctional ectopic tachycardia (JET) is a potentially life‐threatening postoperative arrhythmia in children with specific congenital heart defects and can contribute significantly to postoperative morbidity for at‐risk populations. In adults, β1‐adrenergic receptor (ADRB1) and β2‐adrenergic receptor (ADRB2) genotypes have been associated with increased risk for arrhythmias. However, their association with arrhythmia risk in children is unknown. We aimed to test associations between ADRB1 and ADRB2 genotypes and postoperative JET in patients with congenital heart defects. Children who underwent cardiac surgery were genotyped for the ADRB1 p.Ser49Gly (rs1801252; c.145A>G), p.Arg389Gly (rs1801253; c.1165C>G), ADRB2 p.Arg16Gly (rs1042713; c.46A>G), and p.Glu27Gln (rs1042714; c.79G>C) polymorphisms. The occurrence of postoperative JET was assessed via cardiologist‐interpreted electrocardiograms. Genotype associations with JET were analyzed via logistic regression, adjusted for clinical variables associated with JET, with separate analysis in patients not on a β‐blocker. Of the 343 children included (median age 8 months, 53% boys, 69% European ancestry), 45 (13%) developed JET. The Arg389Arg genotype was not significantly associated with JET in the overall population (odds ratio [OR] = 1.96, 95% confidence interval [CI] = 0.96–4.03, p = 0.064), but was nominally associated in patients not taking a β‐blocker (n = 324, OR = 2.25, 95% CI = 1.05–4.80. p = 0.034). None of the other variants were associated with JET. These data suggest that the ADRB1 Arg389Arg genotype may predict risk for JET following cardiac surgery in pediatric patients in the absence of β‐blockade. Whether treatment with a β‐blocker ameliorates this association requires further research.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

ADRB variants have been associated with arrhythmias in an adult population; however, the contribution of these variants to postoperative arrhythmia risk in children with congenital heart disease is unknown.

• WHAT QUESTION DID THIS STUDY ADDRESS?

Is there an association among ADRB1 Ser49Gly, ADRB1 Arg389Gly, ADRB2 Arg16Gly, or ADRB2 Gln27Glu genotypes and postoperative junctional ectopic tachycardia (JET) occurrence in children undergoing cardiac surgery?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

ADRB1 Arg389Arg genotype may help predict risk for JET following cardiac surgery in pediatric patients in the absence of β‐blockade.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

These findings serve as a foundation for further study of postoperative JET risk and ADRB1 Arg389Arg genotype and suggest a potential role of β‐blockade in reducing genotype‐mediated risk for JET in ADRB1 Arg389Arg genotype patients.     

Restrictive dermopathy: a rare laminopathy

BACKGROUND: Restrictive dermopathy (RD) belongs to the laminopathies and mostly shows an autosomal recessive heredity pattern. This rare genetic disorder is lethal for the newborn in the neonatal period. Clinical and pathological findings are distinctive and allow for a specific diagnosis in most cases. Furthermore, polyhydramnios, decreased foetal movement, facial dysmorphisms and arthrogryposis are characteristic of RD. Respiratory insufficiency leads to an early neonatal death. METHODS: We present the case of an affected infant and a review of the previously reported cases in the literature. RESULTS: The infant showed thin, shiny skin with exfoliating desquamation, a small, round and open mouth, low-set ears, a small pinched nose, joint contractures at all four extremities and distinctive pulmonic atelectasis. It died 3 h and 20 min post-partum. Histologically, the skin showed the typical pattern of an RD with the epidermis covered by an exfoliated, hyperkeratotic horn layer, clearly hypoplastic hair follicles and a considerably reduced dermis thickness, although it had a massive subcutaneous adipose tissue. Electron microscopically, the diagnosis was confirmed. CONCLUSIONS: It is important to know about this disease and to distinguish it from others like keratinization malfunctions such as ichtyosis, congenital, developmental and akinesia disturbance, etc., to know the prognosis for the affected newborn and to provide sufficient (genetic) counselling to the families. This disorder is caused by dominant mutations of the LMNA (primary laminopathy) or recessive mutations of the ZMPSTE24 (FACE1) (secondary laminopathy) genes.     

Alkaloids from the mushroom Pseudobaeospora pyrifera, pyriferines A-C

Three novel alkaloids (1-3), named pyriferines A-C, were isolated from fruiting bodies of Pseudobaeospora pyrifera. They possess an unusual eight-membered N/O-acetal ring, derived from L-glutamic acid, that is connected to an enolized 1,3-diketo moiety. The structures were determined by spectroscopic methods, and the absolute configuration of the glutamic acid moiety was established using GC-MS after Mosher-type derivatization.     

Enhancement of tenogenic differentiation of human adipose stem cells by tendon-derived extracellular matrix

Mesenchymal stem cells (MSCs) have gained increasing research interest for their potential in improving healing and regeneration of injured tendon tissues. Developing functional three-dimensional (3D) scaffolds to promote MSC proliferation and differentiation is a critical requirement in tendon tissue engineering. Tendon extracellular matrix has been shown to maintain the tenogenic potential of tendon stem cells and stimulate tenogenesis of human adipose stem cells (hASCs) in 2D culture. This study aims at characterizing the biological composition of urea-extracted fraction of tendon ECM (tECM) and its tenogenic effect on hASCs cultured in a 3D collagen scaffold under uniaxial tension. The tECM obtained was cell-free and rich in ECM proteins. hASCs seeded in tECM-supplemented scaffold exhibited significantly increased proliferation and tenogenic differentiation. The presence of tECM also greatly suppressed the osteogenic differentiation of hASCs triggered by uniaxial tension. In addition, tECM-supplemented constructs displayed enhanced mechanical strength, accompanied by reduced expression and activity of MMPs in the seeded hASCs, indicating a regulatory activity of tECM in cell-mediated scaffold remodeling. These findings support the utility of tECM in creating bio-functional scaffolds for tendon tissue engineering.     

Text Messages to Curb Sugar-Sweetened Beverage Consumption among Pregnant Women and Mothers: A Mobile Health Randomized Controlled Trial

Racial, ethnic, and socioeconomic disparities in childhood obesity in the United States (U.S.) originate in early life. Maternal sugar-sweetened beverage (SSB) consumption is an early life risk factor for later offspring obesity. The goal of this study was to test the effects of policy-relevant messages delivered by text messages mobile devices (mHealth) on maternal SSB consumption. In this three-arm 1-month randomized controlled trial (RCT), pregnant women or mothers of infants in predominantly Hispanic/Latino New York City neighborhoods were randomized to receive one of three text message sets: graphic beverage health warning labels, beverage sugar content information, or attention control. The main outcome was change in maternal self-reporting of average daily SSB consumption from baseline to one month. Among 262 participants, maternal SSB consumption declined over the 1-month period in all three arms. No intervention effect was detected in primary analyses. In sensitivity analyses accounting for outliers, graphic health warning labels reduced maternal SSB consumption by 28 kcal daily (95% CI: −56, −1). In this mHealth RCT among pregnant women and mothers of infants, graphic health warning labels and beverage sugar content information did not reduce maternal SSB consumption.     

Study of mitochondrial DNA depletion in muscle by single-fiber polymerase chain reaction

We studied muscle biopsies from 3 children with a mitochondrial myopathy characterized histochemically by the presence of ragged-red fibers (RRF) and various numbers of cytochrome c oxidase (COX)-negative fibers. We quantitated the absolute amounts of total mitochondrial DNA (mtDNA) in isolated normal COX-positive muscle fibers and in COX-negative RRF. There was severe mtDNA depletion in all fibers from the two most severe cases. In the third case mtDNA depletion could not be established with conventional diagnostic tools, but it was documented in single COX-negative fibers; COX-positive fibers showed the same amounts of mtDNA as fibers from aged-matched controls. Our observations indicate that mtDNA single-fiber PCR quantitation is a highly sensitive and specific method for diagnosing cases with focal mtDNA depletion. This method also allows one to correlate amounts of mtDNA with histochemical phenotypes in individual fibers from patients and age-matched controls, thereby providing important information about the functional role of residual mtDNA. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1374–1381, 1998     

Repair of porcine articular cartilage defect with a biphasic osteochondral composite.

Autologous chondrocyte implantation (ACI) has been recently used to treat cartilage defects. Partly because of the success of mosaicplasty, a procedure that involves the implantation of native osteochondral plugs, it is of potential significance to consider the application of ACI in the form of biphasic osteochondral composites. To test the clinical applicability of such composite construct, we repaired osteochondral defect with ACI at low cell-seeding density on a biphasic scaffold, and combined graft harvest and implantation in a single surgery. We fabricated a biphasic cylindrical porous plug of DL-poly-lactide-co-glycolide, with its lower body impregnated with beta-tricalcium phosphate as the osseous phase. Osteochondral defects were surgically created at the weight-bearing surface of femoral condyles of Lee-Sung mini-pigs. Autologous chondrocytes isolated from the cartilage were seeded into the upper, chondral phase of the plug, which was inserted by press-fitting to fill the defect. Defects treated with cell-free plugs served as control. Outcome of repair was examined 6 months after surgery. In the osseous phase, the biomaterial retained in the center and cancellous bone formed in the periphery, integrating well with native subchondral bone with extensive remodeling, as depicted on X-ray roentgenography by higher radiolucency. In the chondral phase, collagen type II immunohistochemistry and Safranin O histological staining showed hyaline cartilage regeneration in the experimental group, whereas only fibrous tissue formed in the control group. On the International Cartilage Repair Society Scale, the experimental group had higher mean scores in surface, matrix, cell distribution, and cell viability than control, but was comparable with the control group in subchondral bone and mineralization. Tensile stress-relaxation behavior determined by uni-axial indentation test revealed similar creep property between the surface of the experimental specimen and native cartilage, but not the control specimen. Implanted autologous chondrocytes could survive and could yield hyaline-like cartilage in vivo in the biphasic biomaterial construct. Pre-seeding of osteogenic cells did not appear to be necessary to regenerate subchondral bone.