Mass, Spectroscopy, and Two-Neutron Decay of

The structure and decay of the most neutron-rich beryllium isotope, ^{16}Be, has been investigated following proton knockout from a high-energy ^{17}B beam. Two relatively narrow resonances were observed for the first time, with energies of 0.84(3) and 2.15(5) MeV above the two-neutron decay threshold and widths of 0.32(8) and 0.95(15) MeV, respectively. These were assigned to be the ground (J^{π}=0^{+}) and first excited (2^{+}) state, with E_{x}=1.31(6) MeV. The mass excess of ^{16}Be was thus deduced to be 56.93(13) MeV, some 0.5 MeV more bound than the only previous measurement. Both states were observed to decay by direct two-neutron emission. Calculations incorporating the evolution of the wave function during the decay as a genuine three-body process reproduced the principal characteristics of the neutron-neutron energy spectra for both levels, indicating that the ground state exhibits a strong spatially compact dineutron component, while the 2^{+} level presents a far more diffuse neutron-neutron distribution.

Carbogen inhalation during non-convulsive status epilepticus: A quantitative exploratory analysis of EEG recordings.

OBJECTIVE: To quantify the effect of inhaled 5% carbon-dioxide/95% oxygen on EEG recordings from patients in non-convulsive status epilepticus (NCSE). METHODS: Five children of mixed aetiology in NCSE were given high flow of inhaled carbogen (5% carbon dioxide/95% oxygen) using a face mask for maximum 120s. EEG was recorded concurrently in all patients. The effects of inhaled carbogen on patient EEG recordings were investigated using band-power, functional connectivity and graph theory measures. Carbogen effect was quantified by measuring effect size (Cohen's d) between "before", "during" and "after" carbogen delivery states. RESULTS: Carbogen's apparent effect on EEG band-power and network metrics across all patients for "before-during" and "before-after" inhalation comparisons was inconsistent across the five patients. CONCLUSION: The changes in different measures suggest a potentially non-homogeneous effect of carbogen on the patients' EEG. Different aetiology and duration of the inhalation may underlie these non-homogeneous effects. Tuning the carbogen parameters (such as ratio between CO2 and O2, duration of inhalation) on a personalised basis may improve seizure suppression in future.

Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of Duchenne muscular dystrophy.

Frameshift mutations in the DMD gene, encoding dystrophin, cause Duchenne muscular dystrophy (DMD), leading to terminal muscle and heart failure in patients. Somatic gene editing by sequence-specific nucleases offers new options for restoring the DMD reading frame, resulting in expression of a shortened but largely functional dystrophin protein. Here, we validated this approach in a pig model of DMD lacking exon 52 of DMD (DMDΔ52), as well as in a corresponding patient-derived induced pluripotent stem cell model. In DMDΔ52 pigs1, intramuscular injection of adeno-associated viral vectors of serotype 9 carrying an intein-split Cas9 (ref. 2) and a pair of guide RNAs targeting sequences flanking exon 51 (AAV9-Cas9-gE51) induced expression of a shortened dystrophin (DMDΔ51-52) and improved skeletal muscle function. Moreover, systemic application of AAV9-Cas9-gE51 led to widespread dystrophin expression in muscle, including diaphragm and heart, prolonging survival and reducing arrhythmogenic vulnerability. Similarly, in induced pluripotent stem cell-derived myoblasts and cardiomyocytes of a patient lacking DMDΔ52, AAV6-Cas9-g51-mediated excision of exon 51 restored dystrophin expression and amelioreate skeletal myotube formation as well as abnormal cardiomyocyte Ca2+ handling and arrhythmogenic susceptibility. The ability of Cas9-mediated exon excision to improve DMD pathology in these translational models paves the way for new treatment approaches in patients with this devastating disease.

Surface Localization of the Dineutron in

The formation of a dineutron in the ^{11}Li nucleus is found to be localized to the surface region. The experiment measured the intrinsic momentum of the struck neutron in ^{11}Li via the (p,pn) knockout reaction at 246 MeV/nucleon. The correlation angle between the two neutrons is, for the first time, measured as a function of the intrinsic neutron momentum. A comparison with reaction calculations reveals the localization of the dineutron at r∼3.6 fm. The results also support the density dependence of dineutron formation as deduced from Hartree-Fock-Bogoliubov calculations for nuclear matter.

Extraction of the Landau-Migdal Parameter from the Gamow-Teller Giant Resonance in

The key parameter to discuss the possibility of the pion condensation in nuclear matter, i.e., the so-called Landau-Migdal parameter g^{'}, was extracted by measuring the double-differential cross sections for the (p,n) reaction at 216 MeV/u on a neutron-rich doubly magic unstable nucleus, ^{132}Sn with the quality comparable to data taken with stable nuclei. The extracted strengths for Gamow-Teller (GT) transitions from ^{132}Sn leading to ^{132}Sb exhibit the GT giant resonance (GTR) at the excitation energy of 16.3±0.4(stat)±0.4(syst) MeV with the width of Γ=4.7±0.8 MeV. The integrated GT strength up to E_{x}=25 MeV is S_{GT}^{-}=53±5(stat)_{-10}^{+11}(syst), corresponding to 56% of Ikeda's sum rule of 3(N-Z)=96. The present result accurately constrains the Landau-Migdal parameter as g^{'}=0.68±0.07, thanks to the high sensitivity of the GTR energy to g^{'}. In combination with previous studies on the GTR for ^{90}Zr and ^{208}Pb, the result of this work shows the constancy of this parameter in the nuclear chart region with (N-Z)/A=0.11 to 0.24 and A=90 to 208.

Single nucleotide polymorphisms in long noncoding RNA, ANRIL, are not associated with severe periodontitis but with adverse cardiovascular events among patients with cardiovascular disease.

BACKGROUND AND OBJECTIVE: Biological plausibility of an association between severe periodontitis and cardiovascular disease (CVD) has been proven. Genetic characteristics play an important role in both complex inflammatory diseases. Polymorphisms (single nucleotide polymorphisms [SNPs]) in the long noncoding RNA, antisense noncoding RNA in the INK4 locus (ANRIL), were shown to play a leading role in both diseases. The primary objectives of the study were to assess, among cardiovascular (CV angiographically proven ≥50% stenosis of a main coronary artery) patients, the impact of ANRIL SNPs rs133049 and rs3217992 on the severity of periodontitis and the previous history of coronary events, as well as on the occurrence of further adverse CV events. MATERIAL AND METHODS: The prevalence of severe periodontitis was analyzed in 1002 CV patients. ANRIL SNPs rs133049 and rs3217992 were genotyped. The prognostic value of both ANRIL SNPs for combined CV endpoint (stroke/transient ischemic attack [TIA], myocardial infarction, death from a CV-related event, death from stroke) was evaluated after a 3-year follow-up period. Hazard ratios (HRs) were adjusted for established CV risk factors applying Cox regression. RESULTS: ANRIL SNPs rs133049 and rs3217992 were not associated with severe periodontitis or history of CVD in CV patients. In the Kaplan-Meier survival curve including the log rank-test (P = .036) and Cox regression (hazard ratio = 1.684, P = .009) the AA genotype of rs3217992 was shown to be an independent predictor for adverse CV events after 3 years of follow-up. CONCLUSION: SNPs in ANRIL are not risk modulators for severe periodontitis and history of CVD in CV patients. The AA genotype of ANRIL SNPs rs3217992 possesses prognostic power for further CV events within 3 years of follow-up.

Cytogenetic Effects of Chronic Methylphenidate Treatment and Chronic Social Stress in Adults with Attention-Deficit/Hyperactivity Disorder.

INTRODUCTION: Methylphenidate (MPH) is widely used to treat childhood and adult attention-deficit/hyperactivity disorder (ADHD). However, there are still safety concerns about side effects in long-term treatment. The aim of this study was to assess cytogenetic effects of chronic MPH treatment in adult ADHD and to find out if chronic social stress is attenuated by medication and to investigate whether chronic psychosocial stress leads to mutagenic effects by itself. METHODS: Lymphocytes for micronucleus assay and saliva samples for cortisol measurement were collected from adult ADHD patients and healthy controls. Stress exposure of the last 3 months was assessed by TICS (Trier Inventory for Chronic Stress). RESULTS: We could not detect an influence of MPH treatment on cytogenetic markers. ADHD patients displayed significantly higher chronic stress levels measured by TICS compared to healthy controls which were influenced by duration of MPH treatment. ADHD patients also showed significantly lower basal cortisol levels. DISCUSSION: We could corroborate that there are neither cytogenetic effects of chronic stress nor of chronic MPH intake even after several years of treatment.

[Investigation of metabolic parame- ters in high yielding dairy cows in pasture based production systems]. / Stoffwechseluntersuchungen bei Hochleistungskühen in Vollweidehaltung.

In the present study differences in metabolism between New Zealand Holstein-Friesian (NZHF) and Brown Swiss (CH-BV) or Swiss Holstein-Friesian (CH-HF) were investigated in a grassland based milk production system in Switzerland. Therefore 14 pairs of CH-BV/NZHF and 11 pairs of CH-HF/NZHF were available. The parameters glucose, insulin, non-esterified fatty acids (NEFA), ß-hydroxybutyrate (ß-HB), urea and cholesterol were analysed at the times 5-3 weeks before the calculated partus and 2, 3, 5, 7, 10 and 18-22 weeks post partum. Only ß-HB showed significantly higher concentrations (P = 0.0059) for both Swiss breeds compared to the NZ-HF. Regarding all other physiological parameters during early lactation New Zealand Holstein-Friesians were not different from Swiss breeds.

Maternal telomere length inheritance in the king penguin.

Telomeres are emerging as a biomarker for ageing and survival, and are likely important in shaping life-history trade-offs. In particular, telomere length with which one starts in life has been linked to lifelong survival, suggesting that early telomere dynamics are somehow related to life-history trajectories. This result highlights the importance of determining the extent to which telomere length is inherited, as a crucial factor determining early life telomere length. Given the scarcity of species for which telomere length inheritance has been studied, it is pressing to assess the generality of telomere length inheritance patterns. Further, information on how this pattern changes over the course of growth in individuals living under natural conditions should provide some insight on the extent to which environmental constraints also shape telomere dynamics. To fill this gap partly, we followed telomere inheritance in a population of king penguins (Aptenodytes patagonicus). We tested for paternal and maternal influence on chick initial telomere length (10 days old after hatching), and how these relationships changed with chick age (at 70, 200 and 300 days old). Based on a correlative approach, offspring telomere length was positively associated with maternal telomere length early in life (at 10 days old). However, this relationship was not significant at older ages. These data suggest that telomere length in birds is maternally inherited. Nonetheless, the influence of environmental conditions during growth remained an important factor shaping telomere length, as the maternal link disappeared with chicks' age.

Use of floss/interdental brushes is associated with lower risk for new cardiovascular events among patients with coronary heart disease.

BACKGROUND AND OBJECTIVE: Periodontitis has been found to be associated with coronary heart disease (CHD) and stroke. However, only little is known about whether periodontitis and associated confounders are associated with new cardiovascular events among patients with CHD. MATERIAL AND METHODS: A total of 942 inpatients with CHD were examined regarding periodontitis, oral care habits, bacteria in the subgingival biofilm and the expression of interleukin-(IL)-6 c. (coding DNA)-174 genotypes (rs 1800793) to determine whether these confounders are associated with new cardiovascular events within a 1-year follow-up period. Adjusted hazard ratios (HR) with respect of age, gender, smoking, body mass index, use of aids for interdental hygiene, plaque index, occurrence of severe periodontitis and further internal diseases such as diabetes, hypertension, dyslipoproteinemia, number of missing teeth, serological parameters and IL-6 genotypes were generated with Cox regression. RESULTS: In all, 941 cardiovascular patients completed the 1-year follow up and 7.3% of the patients achieved the primary endpoint (myocardial infarction: 2.1%, stroke/transient ischemic attack: 1.8%, cardiovascular deaths: 3.4%). Patients who reported practicing interdental cleaning were younger, less likely to be male or to have severe periodontitis, had a reduced tobacco exposure, had fewer missing teeth, less indices for plaque and bleeding on probing and a significant decreased adjusted risk for new cardiovascular events (HR = 0.2, CI 0.06-0.6, p = 0.01) than those patients with CHD who did not report practicing interdental cleaning. We did not obtain significant increased HR for patients with severe periodontitis (HR = 1.2, CI 0.7-2.1, p = 0.53), carriers of the IL-6 genotypes GC or CC (HR = 1.4, CI 0.8-2.5, p = 0.24) and did not find a significant association between the number of detected various oral species and the incidence of the combined endpoint (HR = 0.9, CI 0.8-1.01, p = 0.07). CONCLUSIONS: These findings suggest that flossing and brushing of interdental spaces might reduce the risk for new cardiovascular events among patients with CHD. The hypothesis that interdental cleaning per se reduces the risk of new cardiovascular events should be examined in an interventional study.

The role of survivin for radiation oncology: moving beyond apoptosis inhibition.

Alterations in the expression of apoptosis-related proteins, like the inhibitor of apoptosis (IAP) protein family, display a pivotal pathway by which cancer cells acquire resistance to therapeutic treatment. Among this family, survivin, the smallest and structural unique member, deserves growing attention due to its universal over-expression in human tumors, and its prominent role in disparate networks of cellular division, intracellular signaling and apoptosis. Several preclinical studies have demonstrated that targeting survivin expression by the use of small interfering RNAs, dominant negative mutants, antisense-oligonucleotides and small molecule repressors sensitized tumor cells towards chemotherapy and irradiation and reduced tumor growth potential. Due to these properties, survivin has been proposed as a molecular target for anticancer therapies. Recent studies further revealed that radio-sensitization achieved by survivin inhibition seems to be multifaceted and involves caspase-dependent and caspase-independent mechanisms. In general, an enhanced rate of apoptosis, and pronounced cell cycle arrest have been observed. More recently, a hampered DNA-damage response has been noted, indicating a distinct role of the protein in radiation-induced double strand break repair. These properties were linked to a nuclear import and physical interrelationship with members of the DNA-DSB repair machinery such as phospho-histone H2AX and DNA dependent Protein Kinase (DNA-PKcs). The applicability of survivin-driven strategies in clinical practice is currently under investigation as the first survivin inhibitors successfully entered phase I/II trials. Although these trials do not include radiation therapy at present, survivin inhibitors may represent a novel type of molecular antagonists to improve the effectiveness of radiation therapy or chemoradio-therapy.

The del/del genotype of the nuclear factor-kappaB -94ATTG polymorphism and its relation to aggressive periodontitis.

BACKGROUND AND OBJECTIVE: Periodontitis is influenced by specific host-dependent immune responses. Periodontopathogens induce innate immune responses, amongst others, via toll-like receptor 2 (TLR2), resulting in activation of the nuclear transcription factor nuclear factor-kappaB (NF-kappaB). The aim of this case-control study was to evaluate links between genetic variants of these genes and chronic/aggressive periodontitis in a multivariate model. MATERIAL AND METHODS: A total of 141 patients with periodontitis (63 with chronic periodontitis and 78 with aggressive periodontitis) and 81 controls without periodontitis were included in the study. Polymorphisms in TLR2 (Arg677Trp, Arg753Gln) and in NF-kappaB (-94ins/delATTG) were determined by restriction fragment length polymorphism and fragment length analyses, respectively. Subgingival bacterial colonization was evaluated using a PCR/DNA probe test (micro-Ident). RESULTS: Although there was no association of the TLR2 polymorphism Arg753Gln with periodontitis, heterozygous carriers (Arg/Gln) were at a higher risk for colonization with bacteria of the 'red complex' (corrected p-value = 0.042). The del/del genotype of the NF-kappaB polymorphism was associated with aggressive periodontitis considering age, gender, smoking and approximal plaque index as potential confounders (odds ratio = 2.81, p = 0.035, 95% confidence interval: 1.08-7.33). del/del carriers had a higher risk for subgingival colonization with Aggregatibacter actinomycetemcomitans (odds ratio = 2.36, p = 0.030, 95% confidence interval: 1.09-5.1; adjusted for age, gender, smoking and pocket depth(bacteria)). CONCLUSIONS: The del/del genotype of NF-kappaB was shown to be associated with the occurrence of aggressive periodontitis.

Interleukin-2 -330 and 166 gene polymorphisms in relation to aggressive or chronic periodontitis and the presence of periodontopathic bacteria.

BACKGROUND AND OBJECTIVE: As a pro-inflammatory cytokine, interleukin-2 mediates the activation, growth and differentiation of T and B lymphocytes and natural killer cells. Promoter polymorphisms of the interleukin-2 gene have been associated with altered interleukin-2 production or identified as prognostic markers for various infectious diseases. Therefore, the aim of this study was to evaluate two polymorphisms at positions -330 T/G and 166 G/T in patients with generalized chronic periodontitis (n = 58) or generalized aggressive periodontitis (n = 73) in comparison with periodontitis-free controls (n = 69). MATERIAL AND METHODS: Both interleukin-2 polymorphisms were analyzed using the polymerase chain reaction with sequence-specific primers. Distributions of single alleles, genotypes and haplotypes were calculated using the chi-square test. Risk factor analyses were carried out by logistic regression with respect to established cofactors for periodontitis. The presence of subgingival bacteria in an individual were analyzed using a molecular biological method (the micro-Ident test). RESULTS: The interleukin-2 genotype -330 TG occurred less frequently in patients with chronic periodontitis (25.9% vs. 49.3%). Moreover, this genotype decreased the adjusted odds ratio for chronic periodontitis (odds ratio = 0.394), whereas the interleukin-2 genotype 166 TT and the haplotype combination interleukin-2 -330,166 TT : TT were associated with an increased adjusted odds ratio (odds ratio = 2.82 or 2.97). For the latter interleukin-2 combination, a positive association for the subgingival presence of Porphyromonas gingivalis (81.3% vs. 59.5%) and bacteria of the 'red complex' (78.1% vs. 56.0%) was shown. CONCLUSION: The interleukin-2 genotypes -330 TG and 166 TT, as well as the combination genotype interleukin-2 TT : TT, could be putative prognostic factors for chronic periodontitis.

Impact of genetic variants of CD14 and TLR4 on subgingival periodontopathogens.

CD14 and toll-like receptor 4 (TLR4) are involved in host's immune response to bacterial pathogens including periodontal bacteria. Functional important gene polymorphisms are described for both genes. The aim of this study was to evaluate links between genetic polymorphisms of CD14 and TLR4 and risk markers of periodontitis in a multivariate model. One hundred and thirty-three periodontitis patients (chronic: n = 60, aggressive: n = 73) and 80 healthy controls without periodontitis were included in the study. Polymorphisms in CD14 c.-159C>T and in TLR4 Asp299Gly, Thr399Ile were determined by restriction fragment length polymorphism analyses. The clinical investigation included smoking status, plaque and bleeding indexes, pocket depth and attachment loss. Subgingival bacterial colonization was analysed molecularbiologically using the micro-Ident test. Prevotella intermedia occurred less frequently in individuals positive for the TT genotype of CD14 in bivariate analysis (odds ratio = 0.36%, confidence interval: 0.14-0.91, P = 0.045). In binary logistic regression analyses, the occurrence of this bacterium was significantly decreased in TT carriers (odds ratio = 0.31%, confidence interval: 0.81-0.12, P = 0.017) considering age, smoking and maximum clinical attachment loss at microbial test site as confounding factors. However, no significant association with chronic and or aggressive periodontitis and polymorphisms in CD14 and TLR4 could be proven. Although the CD14 c.-159C>T polymorphism could be shown to be associated with subgingival colonization with P. intermedia, there is no evidence that CD14 and TLR4 polymorphisms investigated are independent risk factors for chronic or aggressive periodontitis in German periodontitis patients.

[Pulmonary auscultation in the era of evidence-based medicine]. / L'auscultation pulmonaire à l'ère de la médecine factuelle.

BACKGROUND: Distinction between normal and abnormal respiratory sounds is important for accurate diagnosis. CURRENT DATA: This paper describes the state of the art, scientific publications and ongoing research related to the respiratory sounds. The study includes a description of the various techniques that are being used to record auscultatory sounds and a physical description of known pathological sounds (wheezes and crackles) for which automatic detection tools have been developed. VIEWPOINTS: The next stage will include exploiting all the qualities of the sounds. This augmentation of the spectrum studied, linked to signal analysis techniques, will allow the definition of new characteristic markers.

Molecular and physiological effects of nesiritide.

BACKGROUND: Nesiritide (Natrecor, Janssen-Ortho Inc, Canada), or recombinant human B-type natriurtic peptide (BNP), is a molecule identical in structure to endogenous BNP-32. This peptide is secreted from cardiac myocytes in response to volume and pressure overload. While high levels of circulating BNP are measured by commercially available assays during acute decompensated heart failure (ADHF), the detection of alternate, potentially more active, but undermeasured forms of BNP needs to be considered. AIM: The present review summarizes the molecular and physiological effects of nesiritide in the setting of hospitalized patients with ADHF. In particular, an overview of the molecular structure and circulating isoforms of BNP is given, followed by a discussion of the vasodilatory, renal, antagonistic neurohormonal, pulmonary, anti-inflammatory and cardiac remodelling effects of recombinant human BNP. SUMMARY: Nesiritide has beneficial effects in the treatment of ADHF that go beyond the traditional goals of reducing pulmonary capillary wedge pressure, preload and afterload, and relieving symptoms of dyspnea. Therefore, the unique pharmacological profile of this medication provides an additional treatment option for Canadian patients with ADHF.

A novel HLA-B*57 (B*5714) allele in a healthy male Caucasian individual.

A novel human leucocyte antigen (HLA)-B57 (HLA-B*5714) allele has been identified in a male Caucasian individual from Middle Europe using single allele-specific sequencing strategy. This allele is identical to the HLA-B*570101 allele except for two point mutations in exon 3 at codon 138 (ACG-->ACC) with no amino acid change [persisting threonine (T)] and at codon 171 (TAC-->CAC), resulting in an amino acid change from tyrosine (Y) to histidine (H).