First follow-up of a breakable stent for implantation in infants dedicated for a life-long stay.

OBJECTIVE AND METHODS: The use of conventional metal stents in infants is severely limited by subsequent somatic growth. The use of a breakable balloon expandable stent (BS) designed for initial implant at small diameters but with properties that allow unlimited dilation in line with growth has potential advantages in this patient group. This study reports our experience with this stent between 2010 and 2014. A total of 17 BS were implanted in 14 infants (mean age 4.8 months). All but one stent was placed into the aorta to treat coarctation. RESULTS: All implantations were successful and initial gradients dropped from a mean of 25-6 mm Hg (range from 1-50 down to 0-24 mm Hg). Mean follow-up was 3.3 years (range 5 days to 7 years) with a total cumulative follow-up of 46.7 patient years. Stent redilation was performed a median of 2.5 times (range 0-5). Sixteen stents in 13 patients remain in place. Following redilation beyond 10 mm, circumferential integrity of the BS was lost in 10 patients. No further stent implantation or related surgery was necessary. A 3 mm dissection occurred in one patient after redilation. CONCLUSIONS: The BS performed well in terms of relief of stenosis and could be successfully dilated during the phase of the infants' most rapid growth. Mild intimal proliferation occurred in some patients early after implantation. In the course of the stepwise redilations and growth adjustments, both, planned longitudinal and transverse fractures occurred without allowing a collapse of the stented area.

New class of gene-termini-associated human RNAs suggests a novel RNA copying mechanism.

Small (<200 nucleotide) RNA (sRNA) profiling of human cells using various technologies demonstrates unexpected complexity of sRNAs with hundreds of thousands of sRNA species present. Genetic and in vitro studies show that these RNAs are not merely degradation products of longer transcripts but could indeed have a function. Furthermore, profiling of RNAs, including the sRNAs, can reveal not only novel transcripts, but also make clear predictions about the existence and properties of novel biochemical pathways operating in a cell. For example, sRNA profiling in human cells indicated the existence of an unknown capping mechanism operating on cleaved RNA, a biochemical component of which was later identified. Here we show that human cells contain a novel type of sRNA that has non-genomically encoded 5' poly(U) tails. The presence of these RNAs at the termini of genes, specifically at the very 3' ends of known mRNAs, strongly argues for the presence of a yet uncharacterized endogenous biochemical pathway in cells that can copy RNA. We show that this pathway can operate on multiple genes, with specific enrichment towards transcript-encoding components of the translational machinery. Finally, we show that genes are also flanked by sense, 3' polyadenylated sRNAs that are likely to be capped.

Prosthesis loading after temporomandibular joint replacement surgery: a musculoskeletal modeling study.

One of the most widely reported complications associated with temporomandibular joint (TMJ) prosthetic total joint replacement (TJR) surgery is condylar component screw loosening and instability. The objective of this study was to develop a musculoskeletal model of the human jaw to assess the influence of prosthetic condylar component orientation and screw placement on condylar component loading during mastication. A three-dimensional model of the jaw comprising the maxilla, mandible, masticatory muscles, articular cartilage, and articular disks was developed. Simulations of mastication and a maximum force bite were performed for the natural TMJ and the TMJ after prosthetic TJR surgery, including cases for mastication where the condylar component was rotated anteriorly by 0 deg, 5 deg, 10 deg, and 15 deg. Three clinically significant screw configurations were investigated: a complete, posterior, and minimal-posterior screw (MPS) configuration. Increases in condylar anterior rotation led to an increase in prosthetic condylar component contact stresses and substantial increases in condylar component screw stresses. The use of more screws in condylar fixation reduced screw stress magnitudes and maximum condylar component stresses. Screws placed superiorly experienced higher stresses than those of all other condylar fixation screws. The results of the present study have important implication for the way in which prosthetic components are placed during TMJ prosthetic TJR surgery.

Chromatin profiling by directly sequencing small quantities of immunoprecipitated DNA.

Chromatin structure and transcription factor localization can be assayed genome-wide by sequencing genomic DNA fractionated by protein occupancy or other properties, but current technologies involve multiple steps that introduce bias and inefficiency. Here we apply a single-molecule approach to directly sequence chromatin immunoprecipitated DNA with minimal sample manipulation. This method is compatible with just 50 pg of DNA and should thus facilitate charting chromatin maps from limited cell populations.

Appropriation of the MinD protein-interaction motif by the dimeric interface of the bacterial cell division regulator MinE.

MinE is required for the dynamic oscillation of Min proteins that restricts formation of the cytokinetic septum to the midpoint of the cell in gram negative bacteria. Critical for this oscillation is MinD-binding by MinE to stimulate MinD ATP hydrolysis, a function that had been assigned to the first ∼30 residues in MinE. Previous models based on the structure of an autonomously folded dimeric C-terminal fragment suggested that the N-terminal domain is freely accessible for interactions with MinD. We report here the solution NMR structure of the full-length MinE dimer from Neisseria gonorrhoeae, with two parts of the N-terminal domain forming an integral part of the dimerization interface. Unexpectedly, solvent accessibility is highly restricted for residues that were previously hypothesized to directly interact with MinD. To delineate the true MinD-binding region, in vitro assays for MinE-stimulated MinD activity were performed. The relative MinD-binding affinities obtained for full-length and N-terminal peptides from MinE demonstrated that residues that are buried in the dimeric interface nonetheless participate in direct interactions with MinD. According to results from NMR spin relaxation experiments, access to these buried residues may be facilitated by the presence of conformational exchange. We suggest that this concealment of MinD-binding residues by the MinE dimeric interface provides a mechanism for prevention of nonspecific interactions, particularly with the lipid membrane, to allow the free diffusion of MinE that is critical for Min protein oscillation.

Improved MRI of the neonatal heart: feasibility study using a knee coil.

As a first step towards the development of a neonatal cardiac MRI (CMRI) coil, we investigated the utilization, handling and image quality of a knee coil for CMRI in infants at 3 Tesla. Scout imaging and cine imaging with optimized pulse sequence parameters were performed in two neonates and the resulting images were evaluated for diagnostic purposes. All images were of high diagnostic quality. Complete examinations took less than five minutes. The excellent signal-to-noise ratio provided by this coil allowed all cine studies to be acquired with only three averages. In conclusion, a knee coil can be successfully applied in neonates for CMRI, but the coil design could be improved further to facilitate routine clinical use.

Early implant placement with simultaneous guided bone regeneration following single-tooth extraction in the esthetic zone: 12-month results of a prospective study with 20 consecutive patients.

BACKGROUND: Early implant placement is one of the treatment options in postextraction sites in the anterior maxilla. Implant placement is performed after a soft tissue healing period of 4 to 8 weeks. Implant placement is combined with a simultaneous guided bone regeneration (GBR) procedure to rebuild esthetic facial hard and soft tissue contours. METHODS: In this prospective case-series study, 20 consecutive patients treated with an implant-borne single crown were prospectively followed for 12 months. Clinical, radiologic, and esthetic parameters were recorded to assess treatment outcomes. RESULTS: At the 12-month examination, all 20 implants were successfully integrated, demonstrating ankylotic stability and healthy peri-implant soft tissues as documented by standard parameters. The esthetic outcomes assessed by a pink esthetic score (PES) and a white esthetic score (WES) demonstrated pleasing results overall. The WES values were slightly superior to the PES values. The periapical radiographs showed minimal crestal bone loss around the used bone level implants, with mean bone loss of 0.18 mm at 12 months. Only one implant showed >0.5 mm bone loss, combined with minor mucosal recession of 0.5 to 1.0 mm. CONCLUSIONS: This prospective case series study evaluating the concept of early implant placement demonstrated successful tissue integration for all 20 implants. The short-term follow-up of 12 months revealed pleasing esthetic outcomes overall, as assessed by objective parameters. The risk for mucosal recession was low; only one patient showed minor recession of the facial mucosa. These encouraging results need to be confirmed with 3- and 5-year follow-up examinations.

Promising Outcome of Anatomic Correction of Corrected Transposition of the Great Arteries.

BACKGROUND: Anatomic correction of corrected transposition of the great arteries with associated lesions, utilizing the morphologic left ventricle as a systemic pumping chamber, is the preferred method in many centers. The purpose of this study was to analyze functional outcome after anatomic correction. METHODS: Between Jan 1997 and May 2016, 63 patients with corrected transposition of the great arteries and associated lesions underwent anatomic correction. Forty-two patients (67%) underwent palliation before correction, including 14 patients (22%) who required training of systemic ventricle. The double switch procedure was performed in 37 patients; 25 patients underwent the Senning-Rastelli operation, and 1 patient underwent the Senning-Nikaidoh procedure. The median age at correction was 1.6 ± 3.7(SD) years (range, 0.2 to 17.8 years). RESULTS: The survival and freedom from any event was 95% and 71%, respectively, at 15-year follow-up. The combined freedom from death, failure of systemic ventricle, or heart transplant was 93% at 15-year follow-up regardless of procedure type. Sinus rhythm was present in 49 patients, with 14 patients requiring pacemaker (22%)-8 preoperatively, 4 early postoperatively, and 2 late postoperatively. Neurological development is normal in all patients. Fifty-four percent of the patients are not on medication. CONCLUSIONS: Anatomic correction of corrected transposition of the great arteries is a safe procedure that provides encouraging survival and functional benefits. Ninety-three percent preservation of morphological left ventricle function in 15 years of follow-up supports the concept of anatomic correction. Longer follow-up is needed to confirm superiority of this approach over other management strategies.

Is the Lecompte technique the last word on transposition of the great arteries repair for all patients? A magnetic resonance imaging study including a spiral technique two decades postoperatively.

OBJECTIVES: To compare the Lecompte technique and the spiral anastomosis (complete anatomic correction) two decades after arterial switch operation (ASO). METHODS: Nine patients after primary ASO with Lecompte and 6 selected patients after spiral anastomosis were evaluated 20.8 ± 2.1 years after ASO versus matched controls. Blood flow dynamics and flow profiles (e.g. vorticity, helicity) in the great arteries were quantified from time-resolved 3D magnetic resonance imaging (MRI) phase contrast flow measurements (4D flow MR) in addition to a comprehensive anatomical and functional cardiovascular MRI analysis. RESULTS: Compared with spiral reconstruction, patients with Lecompte showed more vortex formation, supranatural helical blood flow (relative helicity in aorta: 0.036 vs 0.089; P < 0.01), a reduced indexed cross-sectional area of the left pulmonary artery (155 vs 85 mm²/m²; P < 0.001) and more semilunar valve dysfunctions (n = 5 vs 1). There was no difference in elastic aortic wall properties, ventricular function, myocardial perfusion and myocardial fibrosis between the two groups. Cross-sectional area of the aortic sinus was larger in patients than in controls (669 vs 411 mm²/m²; P < 0.01). In the spiral group, the pulmonary root was rotated after ASO more towards the normal left position (P < 0.01). CONCLUSIONS: In this study, selected patients with spiral anastomoses showed, two decades after ASO, better physiologically adapted blood flow dynamics, and attained a closer to normal anatomical position of their great arteries, as well as less valve dysfunction. Considering the limitations related to the small number of patients and the novel MRI imaging techniques, these data may provoke reconsidering the optimal surgical approaches to transposition of the great arteries repair.

The use of psychosocial interventions.

It has been recognised that the management of severe mental illness should not only involve medication, but psychosocial interventions (PSI). These interventions draw techniques from cognitive behavioural therapies (CBT) and educational theories. They assume that there is a complex interplay between biological, environmental and sociological factors and that ambient stress together with certain life events may trigger an onset or relapse of mental health problems in some people (Neuchterlein and Dawson, 1984; Zubin and Spring, 1977).

A high isoflavone diet decreases 5' adenosine monophosphate-activated protein kinase activation and does not correct selenium-induced elevations in fasting blood glucose in mice.

Selenium (Se) has been implicated as a micronutrient that decreases adenosine monophosphate-activated protein kinase (AMPK) signaling and may increase diabetes risk by reducing insulin sensitivity. Soy isoflavones (IF) are estrogen-like compounds that have been shown to attenuate insulin resistance, hyperglycemia, adiposity, and increased AMPK activation. We hypothesized that a high IF (HIF) diet would prevent the poor metabolic profile associated with high Se intake. The purpose of this study was to examine changes in basal glucose metabolism and AMPK signaling in response to an HIF diet and/or supplemental Se in a mouse model. Male FVB mice were divided into groups receiving either a control diet with minimal IF (low IF) or an HIF diet. Each dietary group was further subdivided into groups receiving either water or Se at a dose of 3 mg Se/kg body weight daily, as Se-methylselenocysteine (SMSC). After 5 months, mice receiving SMSC had elevated fasting glucose (P < .05) and a tendency for glucose intolerance (P = .08). The increase in dietary IF did not result in improved fasting blood glucose. Interestingly, after 6 months, HIF-fed mice had decreased basal AMPK activation in liver and skeletal muscle tissue (P < .05). Basal glucose metabolism was changed by SMSC supplementation as evidenced by increased fasting blood glucose and glucose intolerance. High dietary IF levels did not protect against aberrant blood glucose. In FVB mice, decreased basal AMPK activation is not the mechanism through which Se exerts its effect. These results suggest that more research must be done to elucidate the role of Se and IF in glucose metabolism.

Error tolerant indexing and alignment of short reads with covering template families.

The rapid adoption of high-throughput next generation sequence data in biological research is presenting a major challenge for sequence alignment tools­specifically, the efficient alignment of vast amounts of short reads to large references in the presence of differences arising from sequencing errors and biological sequence variations. To address this challenge, we developed a short read aligner for high-throughput sequencer data that is tolerant of errors or mutations of all types­namely, substitutions, deletions, and insertions. The aligner utilizes a multi-stage approach in which template-based indexing is used to identify candidate regions for alignment with dynamic programming. A template is a pair of gapped seeds, with one used with the read and one used with the reference. In this article, we focus on the development of template families that yield error-tolerant indexing up to a given error-budget. A general algorithm for finding those families is presented, and a recursive construction that creates families with higher error tolerance from ones with a lower error tolerance is developed.