Slowly fading super-luminous supernovae that are not pair-instability explosions.

Super-luminous supernovae that radiate more than 10(44) ergs per second at their peak luminosity have recently been discovered in faint galaxies at redshifts of 0.1-4. Some evolve slowly, resembling models of 'pair-instability' supernovae. Such models involve stars with original masses 140-260 times that of the Sun that now have carbon-oxygen cores of 65-130 solar masses. In these stars, the photons that prevent gravitational collapse are converted to electron-positron pairs, causing rapid contraction and thermonuclear explosions. Many solar masses of (56)Ni are synthesized; this isotope decays to (56)Fe via (56)Co, powering bright light curves. Such massive progenitors are expected to have formed from metal-poor gas in the early Universe. Recently, supernova 2007bi in a galaxy at redshift 0.127 (about 12 billion years after the Big Bang) with a metallicity one-third that of the Sun was observed to look like a fading pair-instability supernova. Here we report observations of two slow-to-fade super-luminous supernovae that show relatively fast rise times and blue colours, which are incompatible with pair-instability models. Their late-time light-curve and spectral similarities to supernova 2007bi call the nature of that event into question. Our early spectra closely resemble typical fast-declining super-luminous supernovae, which are not powered by radioactivity. Modelling our observations with 10-16 solar masses of magnetar-energized ejecta demonstrates the possibility of a common explosion mechanism. The lack of unambiguous nearby pair-instability events suggests that their local rate of occurrence is less than 6 × 10(-6) times that of the core-collapse rate.

GPT2 mutations cause developmental encephalopathy with microcephaly and features of complicated hereditary spastic paraplegia.

Various genetic defects can cause intellectual and developmental disabilities (IDDs). Often IDD is a symptom of a more complex neurodevelopmental or neurodegenerative syndrome. Identifying syndromic patterns is substantive for diagnostics and for understanding the pathomechanism of a disease. Recessive glutamate pyruvate transaminase (GPT2) mutations have recently been associated with IDD in 4 families. Here, we report a novel recessive GPT2 stop mutation p.Gln24* causing a complex IDD phenotype in a homozygous state in 5 patients from 2 consanguineous Arab families. By compiling clinical information of these individuals and previously described GPT2 patients a recognizable neurodevelopmental and potentially neurodegenerative phenotype can be assigned consisting of intellectual disability, pyramidal tract affection with spastic paraplegia, microcephaly and frequently epilepsy. Because of the consistent presence of pyramidal tract affection in GPT2 patients, we further suggest that GPT2 mutations should be considered in cases with complex hereditary spastic paraplegia.

An ultraviolet-optical flare from the tidal disruption of a helium-rich stellar core.

The flare of radiation from the tidal disruption and accretion of a star can be used as a marker for supermassive black holes that otherwise lie dormant and undetected in the centres of distant galaxies. Previous candidate flares have had declining light curves in good agreement with expectations, but with poor constraints on the time of disruption and the type of star disrupted, because the rising emission was not observed. Recently, two 'relativistic' candidate tidal disruption events were discovered, each of whose extreme X-ray luminosity and synchrotron radio emission were interpreted as the onset of emission from a relativistic jet. Here we report a luminous ultraviolet-optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696. The observed continuum is cooler than expected for a simple accreting debris disk, but the well-sampled rise and decay of the light curve follow the predicted mass accretion rate and can be modelled to determine the time of disruption to an accuracy of two days. The black hole has a mass of about two million solar masses, modulo a factor dependent on the mass and radius of the star disrupted. On the basis of the spectroscopic signature of ionized helium from the unbound debris, we determine that the disrupted star was a helium-rich stellar core.

PIK3R1 mutations in SHORT syndrome.

SHORT syndrome (OMIM 269880) is a rare autosomal-dominant disorder characterized by short stature, hyperextensibility of joints, hernias, ocular depression, ophthalmic anomalies (Rieger anomaly, posterior embryotoxon, glaucoma), teething delay, partial lipodystrophy, insulin resistance and facial dysmorphic signs. Heterozygous mutations in PIK3R1 were recently identified in 14 families with SHORT syndrome. Eight of these families had a recurrent missense mutation (c.1945C>T; p.Arg649Trp). We report on two unrelated patients with typical clinical features of SHORT syndrome and additional problems such as pulmonary stenosis and ectopic kidney. Analysis of PIK3R1 revealed the mutation c.1945C>T; p.Arg649Trp de novo in both patients. These two patients not only provide additional evidence that PIK3R1 mutations cause SHORT syndrome, but also broaden the clinical spectrum of this syndrome and further confirm that the amino acid exchange c.1945C>T; p.Arg649Trp is a hotspot mutation in this gene.

Macrocephaly, obesity, mental (intellectual) disability, and ocular abnormalities: alternative definition and further delineation of MOMO syndrome.

MOMO syndrome, previously defined as Macrosomia, Obesity, Macrocephaly, and Ocular abnormalities (OMIM 157980) is a rare intellectual disability syndrome of unknown cause. We describe two further patients with MOMO syndrome. Reported data of patients with MOMO syndrome and our own findings indicate that overgrowth does not appear to be a specific feature. We propose to form the acronym "MOMO" from Macrocephaly, Obesity, Mental (intellectual) disability, and Ocular abnormalities, excluding macrosomia from the syndrome name. The combination of obesity, macrocephaly, and colobomas is unique, therefore these features can be used as major diagnostic criteria of MOMO syndrome.

Long gamma-ray bursts and core-collapse supernovae have different environments.

When massive stars exhaust their fuel, they collapse and often produce the extraordinarily bright explosions known as core-collapse supernovae. On occasion, this stellar collapse also powers an even more brilliant relativistic explosion known as a long-duration gamma-ray burst. One would then expect that these long gamma-ray bursts and core-collapse supernovae should be found in similar galactic environments. Here we show that this expectation is wrong. We find that the gamma-ray bursts are far more concentrated in the very brightest regions of their host galaxies than are the core-collapse supernovae. Furthermore, the host galaxies of the long gamma-ray bursts are significantly fainter and more irregular than the hosts of the core-collapse supernovae. Together these results suggest that long-duration gamma-ray bursts are associated with the most extremely massive stars and may be restricted to galaxies of limited chemical evolution. Our results directly imply that long gamma-ray bursts are relatively rare in galaxies such as our own Milky Way.

Mosaic trisomy 21/monosomy 21 in a living female infant.

Many autosomal monosomies are presumed to end in arrested growth in the first few mitoses, prior even to the time of implantation, with possibly some proceeding to the stage of occult abortion. The single exception may be monosomy 21, although this has been questioned, with most earlier reports of monosomy 21 recently re-interpreted as being due to an unbalanced translocation involving chromosome 21. Here we report a female infant with a mosaic trisomy 21/monosomy 21 karyotype. While the karyotype 46,XX,i(21)(q10) is detected in all metaphases investigated in lymphocytes, mosaicism with the karyotype 46,XX,i(21)(q10)[31]/45,XX, -21[12] is seen in fibroblasts from a skin biopsy. Dysmorphic facial features and multiple malformations remarkably resemble cases of monosomy 21 that have been described in the literature. This suggests a dominant phenotypic effect of loss of one chromosome 21. Detailed clinical description, results of gene dosage studies, and cytogenetic analysis will be presented.

Biocompatibility and thermodynamic properties of PEGDA and two of its copolymer.

During the last years substantial effort was taken in order to provide an effective and safe pharmacotherapy that can be adjusted to the individual needs of patients. Stereolithography is a simple and accurate additive manufacturing technology. According to these characteristics, it may offer unique opportunities for the industrial fabrication of structured drug delivery systems (DDS), which can be tailored to individual needs. During the stereolithographic process photopolymerizable biomaterial is transformed, layer by layer, into the designed polymer DDS. Combined with inkjet printing in an innovative 3D building system it enables selective and precise incorporation of the drug depot into the basic body of the DDS. Poly(ethylene glycol) diacrylate (PEGDA), a hydrophilic and low-immunogenic compound, is a suitable material as drug depot in a photopolymerizable basic biomaterial for this purpose. By combination of PEGDA with other acrylates, the physical properties of the DDS can be adjusted towards the desired characteristics. Therefore, it should be possible to modify the drug release profile through the positioning of drug depots and the diffusion of the drug and adjust it for a wide range of applications. In this study we investigated basic biological and thermodynamic properties of conventionally photocured systems consisting of PEGDA and its coacrylates: 1,3-butanediol diacrylate and pentaerythritol triacrylate. Our preliminary outcomes demonstrate the hydrophilic character of the samples and the importance of a rinsing process. They also show that the addition of different amounts of co-monomers influence the glass transition temperature, which increases with increasing content of coacrylate. Therefore, PEGDA/comonomer composition can be used as a tool for the modification of drug release properties. Consequently, these materials may be regarded as interesting and promising components for DDS via novel additive manufacturing with the ability of highly controlled drug release.

Numerical simulation of the electric field distribution in an electrical stimulation device for scaffolds settled with cartilaginous cells.

Electrical stimulation is a promising approach to enhance cell viability and differentiation. We aim to develop a stimulation device for the investigation and realization of cartilaginous cell engineering. The stimulation setup is capable of applying well-defined electric fields to several scaffolds at the same time. The setup consists of a flat plate with multiple test tubes for the scaffolds. A flexible printed circuit board containing a separate pair of electrodes for each tube is fixed at the bottom of the plate. In this context, numerical simulation using Finite Element Method (FEM) is a valuable tool to gain a better understanding of the electric field distribution in such devices. The thin insulating layer of the flexible printed circuit board allows sufficient field strength to be achieved at moderate input voltages but presents challenges for modelling. In simulations, thin layers would usually require a fine discretization with many degrees of freedom (DOF). This leads to large models, which are expensive regarding memory and computation time. Based on the 'contact impedance' boundary condition available in COMSOL Multiphysics® 5.4, an alternative approach is proposed that can model thin layers in capacitively coupled setups. The resulting electric field distribution in the new stimulation setup is presented and discussed.

Beating heart operations including hybrid revascularization: initial experiences.

BACKGROUND: The outcome of patients (n = 45) with coronary one- to three-vessel disease undergoing beating heart operations using a recently developed stabilizing device was investigated. METHODS: Left internal mammary artery-to-left anterior descending coronary artery (LIMA-to-LAD) revascularization was carried out alone (n = 31) or as hybrid procedure in combination with a balloon angioplasty (n = 14). RESULTS: All 45 patients underwent a successful LIMA-to-LAD procedure without intraoperative complication during a 21 +/- 8-minute (range, 10 to 53 minutes) LAD occlusion time. In 14 hybrid procedures a total of 19 stenoses including 3 left main stenoses were treated successfully by percutaneous transluminal coronary angioplasty and stenting. The postoperative courses were uneventful with the exception of two surgical reexplorations necessitated by bleeding. No worsening of renal, neurologic, or respiratory functions occurred in any patient. In the group having a single LIMA-to-LAD procedure, early postoperative coronary angiograms (22 of 31) showed a patent LIMA graft and excellent anastomosis; this was also true in 4 patients 12 months after operation as shown in angiograms. All patients undergoing hybrid revascularization demonstrated a patent LIMA-to-LAD anastomosis; in 1 patient there was a dissection in the midlevel of the LIMA, which was stented successfully. The 6-month follow-up angiograms in 7 of 14 patients revealed open LIMA bypass grafts in all patients except 1, who was stented because of dissection. CONCLUSIONS: These data indicate that a beating heart operation including hybrid revascularization is safe and effective in selected patients with coronary one- to three-vessel disease including left main stenosis. This approach may be especially advantageous in comparison with conventional coronary artery bypass grafting in patients with severe concomitant disease.

Investigations on properdin activity in the mature and premature newborns with the intrauterine infection.

Properdin level was determined in amniotic fluid, venous blood serum of mothers, umbilical cord blood serum and venous blood of 4-day-old newborns infected intrauterinally. Investigations were performed in 30 babies born at term and 15 premature babies born in the 31st-37th weeks of pregnancy. The control group comprised 30 mature and 15 premature healthy babies. It was observed that among the mature as well as premature infants, in the cases of the intrauterine infections properdin level, was significantly higher in venous blood serum of mothers and venous blood of 4-day-old infants. However, no significant changes in properdin level in umbilical cord blood were noted.

Biomonitoring results and cytogenetic markers among harbour workers with potential exposure to river silt aerosols.

BACKGROUND: Workers on dredgers and lighters on rivers are potentially exposed to a variety of substances. AIMS: To determine the internal load of heavy metals and arsenic as well as levels of cytogenetic markers in workers exposed to river silt aerosols. METHODS: One hundred exposed workers were examined up to eight times within three years. Additionally, 100 control workers were studied once. Blood samples were analysed for lead, mercury, and cadmium. Additionally, micronuclei frequency and sister chromatid exchange (SCE) rates were determined. Urinary samples were analysed for cadmium, mercury, nickel, chromium, and arsenic. Information on potential confounders, such as smoking habits and consumption of fish were assessed. RESULTS: Apart from some increased concentrations of mercury in blood (maximum 14.6 microg/l) and arsenic in urine (maximum 356.5 microg/l) all measurements were within reference values. None of the exposure and effect markers were found to be significantly increased in exposed workers compared to non-exposed controls. In multiple linear regression models, mercury levels in blood as well as the concentration of arsenic in urine were strongly related to fish consumption. Cadmium levels in blood as well as urinary cadmium concentrations were strongly related to smoking habits. After adjusting for smoking habits, SCE rates were associated with cadmium levels in blood. CONCLUSION: Increased exposure levels or enhanced levels of cytogenetic markers were not found in workers exposed to river silt aerosols. However, cadmium exposure in blood was related to SCE frequency.

A new method for coronary occlusion and local stabilization during minimally invasive LIMA-to-LAD-bypass.

The minimally invasive direct coronary occlusion and stabilizing technique (midCOAST)-system, a new device for coronary occlusion and local stabilization during minimally invasive LIMA-to-LAD-bypass is presented. A closed platform with an oval opening in its center provides optimal immobilization together with platform-fixed vessel-loops, which are used for LAD-occlusion. Clinical results in 72 consecutive patients indicate that the midCOAST-device can be safely and effectively used for minimally invasive LIMA-to-LAD-procedure, even in patients with impaired left ventricular function. Due to the optimal immobilization of the target area the quality of the LIMA-to-LAD-anastomosis, documented by post-operative angiography (62/72), was excellent in all cases.

Mirror-image asymmetry in monozygotic twins with kabuki syndrome.

Kabuki syndrome (OMIM 147920) is a rare disorder characterised by moderate intellectual disability, growth retardation, microcephaly and characteristic facial dysmorphic features which comprise long palpebral fissures, eversion of the lateral third of the eyelids and arched eyebrows with lateral sparseness. Mutations in MLL2 are the most frequent cause of this disorder. More than 100 MLL2 point mutations have been reported, but large intragenic deletions comprising one or more exons have not yet been identified. We report on a pair of monozygotic twin brothers in whom a deletion of 2 neighbouring exons was detected. The twins had the characteristic facial features of Kabuki syndrome, and they suffered from microcephaly, cleft lip and palate and congenital heart disease. Cleft lip and palate were left-sided in the first twin and right-sided in the second twin, i.e. they represented a mirror-image asymmetry. The intragenic deletion in these brothers broadens the spectrum of MLL2 mutations, and they provide a rare example of mirror-image asymmetry of congenital malformations in monozygotic twins.