One year follow-up of the multi-centre European PARTNER transcatheter heart valve study

BackgroundTranscatheter aortic valve implantation (TAVI) has emerged as a new therapeutic option in high-risk patients with severe aortic stenosis.AimsPARTNER EU is the first study to evaluate prospectively the procedural and mid-term outcomes of transfemoral (TF) or transapical (TA) implantation of the Edwards SAPIEN® valve involving a multi-disciplinary approach.Methods and resultsPrimary safety endpoints were 30 days and 6 months mortality. Primary efficacy endpoints were haemodynamic and functional improvement at 12 months. One hundred and thirty patients (61 TF, 69 TA), aged 82.1 ± 5.5 years were included. TA patients had higher logistic EuroSCORE (33.8 vs. 25.7, P <0.0005) and more peripheral disease (49.3 vs. 16.4, P< 0.0001). Procedures were aborted in four TA (5.8) and six TF cases (9.8). Valve implantation was successful in the remaining patients in 95.4 and 96.4, respectively. Thirty days and 6 months survival were 81.2 and 58.0 (TA) and 91.8 and 90.2 (TF). In both groups, mean aortic gradient decreased from 46.9 ± 18.1 to 10.9 ± 5.4 mmHg 6 months post-TAVI. In total, 78.1 and 84.8 of patients experienced significant improvement in New York Heart Association (NYHA) class, whereas 73.9 and 72.7 had improved Kansas City Cardiomyopathy Questionnaire (KCCQ) scores in TA and TF cohorts, respectively.ConclusionThis first team-based multi-centre European TAVI registry shows promising results in high-risk patients treated by TF or TA delivery. Survival rates differ significantly between TF and TA groups and probably reflect the higher risk profile of the TA cohort. Optimal patient screening, approach selection, and device refinement may improve outcomes

Reconstitution of DNA Strand Exchange Mediated by Rhp51 Recombinase and Two Mediators

In the fission yeast Schizosaccharomyces pombe, genetic evidence suggests that two mediators, Rad22 (the S. pombe Rad52 homolog) and the Swi5-Sfr1 complex, participate in a common pathway of Rhp51 (the S. pombe Rad51 homolog)–mediated homologous recombination (HR) and HR repair. Here, we have demonstrated an in vitro reconstitution of the central step of DNA strand exchange during HR. Our system consists entirely of homogeneously purified proteins, including Rhp51, the two mediators, and replication protein A (RPA), which reflects genetic requirements in vivo. Using this system, we present the first robust biochemical evidence that concerted action of the two mediators directs the loading of Rhp51 onto single-stranded DNA (ssDNA) precoated with RPA. Dissection of the reaction reveals that Rad22 overcomes the inhibitory effect of RPA on Rhp51-Swi5-Sfr1–mediated strand exchange. In addition, Rad22 negates the requirement for a strict order of protein addition to the in vitro system. However, despite the presence of Rad22, Swi5-Sfr1 is still essential for strand exchange. Importantly, Rhp51, but neither Rad22 nor the Swi5-Sfr1 mediator, is the factor that displaces RPA from ssDNA. Swi5-Sfr1 stabilizes Rhp51-ssDNA filaments in an ATP-dependent manner, and this stabilization is correlated with activation of Rhp51 for the strand exchange reaction. Rad22 alone cannot activate the Rhp51 presynaptic filament. AMP-PNP, a nonhydrolyzable ATP analog, induces a similar stabilization of Rhp51, but this stabilization is independent of Swi5-Sfr1. However, hydrolysis of ATP is required for processive strand transfer, which results in the formation of a long heteroduplex. Our in vitro reconstitution system has revealed that the two mediators have indispensable, but distinct, roles for mediating Rhp51 loading onto RPA-precoated ssDN

Trajectory Estimation for Particles Observed in the Vicinity of (101955) Bennu

We analyze the trajectories of 313 particles seen in the near‐Bennu environment between December 2018 and September 2019. Of these, 65% follow sub‐orbital trajectories, 20% undergo more than one orbital revolution around the asteroid, and 15% directly escape on hyperbolic trajectories. The median lifetime of these particles is ~6 h. The trajectories are sensitive to Bennu's gravitational field, which allows us to reliably estimate the spherical harmonic coefficients through degree 8 and to resolve nonuniform mass distribution through degree 3. The particles are perturbed by solar radiation pressure, enabling effective area‐to‐mass ratios to be estimated. By assuming that particles are oblate ellipsoids of revolution, and incorporating photometric measurements, we find a median axis ratio of 0.27 and diameters for equivalent‐volume spheres ranging from 0.22‐‐6.1 cm, with median 0.74 cm. Our size distribution agrees well with that predicted for fragmentation due to diurnal thermal cycling. Detailed models of known accelerations do not produce a match to the observed trajectories, so we also estimate empirical accelerations. These accelerations appear to be related to mismodeling of radiation pressure, but we cannot rule out contributions from mass loss. Most ejections take place at local solar times in the afternoon and evening (12:00‐‐24:00), although they occur at any time of day. We independently identify ten ejection events, some of which have previously been reported. We document a case where a particle ricocheted off the surface, revealing a coefficient of restitution 0.57±0.01 and demonstrating that some apparent ejections are not related to surface processes

Prevalencija infekcije Neisseriom gonorrhoeae ili Chlamydiom trachomatis kod akutnoga mukopurulentnog cervicitisa

The aim of this study was to determine the incidence of N. gonorrhoae (NG) and/or C. trachomatis (CT) in acute mucopurulent cervicitis (MPC). The study included 617 non-pregnant women with MPC, who had not been receiving any antimicrobial treatment. The average age of patients was 22.2 years. There were no statistically significant differences according to place of residence, education, and marital status. Samples for laboratory analysis were collected using a routine procedure; NG was identified using the cytochrome oxidase test and Gram staining. CT was isolated on McCoy cell culture and stained with Lugol solution. NG was isolated in three women (0.8 %) and CT in 58 women (9.4 %). Fifty-six of the CT-positive patients were nullipara and only two were unipara. All NG-positive patients were also nullipara. The mean number of sexual partners was 2.2 in all study subjects, 2.4 in CT-positive subjects, and 2.9 in NG-positive subjects. Vaginal discharge purity according to Schröder was significantly deteriorated in CT-positive patients (p=0.011). When asked about the use of contraceptives, as many as 32.7 % patients answered that they did not use any protection, 39 % women used the rhythm method and coitus interruptus, 20 % were taking oral contraceptives, 6.1 % used mechanical devices, and 1.9 % used chemical protection. Previous acute and chronic pelvic infl ammatory diseases correlated with MPC (p<0.01). Our statistical analysis suggests that chlamydial infection significantly reduces the purity of vaginal discharge, which is more pronounced in nulliparae. Pap smear was not specific enough to demonstrate chlamydial infection. In view of the MPC findings, the prevalence of CT and NG infection is low.Cilj istraživanja jest utvrditi koincidenciju N. gonorrhoae (NG) i/ili C. trachomatis (CT) u akutnim mukopurulentnim cervicitisima (MPC). Istraživanje je provedeno na populaciji 617 žena izvan trudnoće koje prethodno nisu uzimale antimikrobnu terapiju. NG i CT su izolirane iz obrisaka vrata maternice primjenom standardnih metoda. NG je transportirana na selektivnoj hranjivoj podlozi i identificirana citokrom-oksidaznim testom bojenjem po Gramu. CT je izolirana McCoyevom staničnom kulturom nakon bojenja Lugolovom otopinom. NG je izolirana u tri ispitanice (0,8 %), a CT u 58 ispitanica (9,4 %). Srednja dob bolesnica iznosila je 22,2 godine. Školovanje i bračno stanje nisu statistički značajno utjecali na rezultate istraživanja. Među bolesnicama s izoliranom CT prevladavaju nulipare, a u slučaju NG sve su pozitivne bolesnice također bile nulipare. Srednja vrijednost broja partnera za čitavu populaciju iznosi 2,2. Bolesnice s potvrđenom CT imale su prosječno 2,4, a one s potvrđenom NG 2,9 partnera. Vrijednost određivanja stupnja čistoće rodničkog iscjetka po Schroderu značajno je povišena u CT-pozitivnih bolesnica (p=0.011). Utvrđeno je da 32.7 % ispitanica uopće nije koristilo kontracepciju, dok je većina (39 %) rabila ritmičke metode i prekinuti snošaj. Preostale ispitanice uzimale su oralne kontraceptive (20 %), mehaničku zaštitu (6,1 %) ili lokalne kemijske kontraceptive (1,9 %). Također je dokazano da prethodna akutna i kronična zdjelična upalna bolest korelira s MPC-om (p<0.01). Zaključeno je da klamidijska infekcija statistički značajno korelira sa stupnjem čistoće rodničkog iscjetka, posebice u nulipara. Papanicolaouov razmaz nije specifičan u određivanju klamidijske infekcije. Rezultati istraživanja pokazuju da je učestalost klamidijske i gonokokne infekcije ipak relativno niska u odnosu na nalaz MPC-a

The clinical diagnosis of pelvic inflammatory disease – reuse of electronic medical record data from 189 patients visiting a Swedish university hospital emergency department

BACKGROUND: The pelvic inflammatory disease (PID) diagnosis is mostly based on clinical findings. However, few studies have examined the clinical basis for the diagnostics of PID, which was the aim of this study. METHODS: A retrospective study was performed of 189 out-patients diagnosed as having PID at the obstetric and gynecological emergency department of a Swedish university hospital. Data on symptoms, signs, pelvic examination and laboratory tests were extracted from the electronic medical records in comparison with the diagnostic criteria of the PID Guideline of the US Center of Disease Control from 2002 (CDC 2002 Guidelines). RESULTS: Eight symptoms in varying combinations were associated with the PID diagnosis. Most of them are mentioned in the CDC 2002 Guidelines. Detected rates of C. Trachomatis (CT) and N. Gonorrhoeae (NG) were 5% and 0%, respectively, among the tested patients (CT = 52% and NG = 12%). The C-reactive protein was normal in the majority of tested patients. CONCLUSION: The clinical basis for the diagnostics of PID was largely in accordance with the criteria in the CDC 2002 Guidelines. The limited number of CT tests performed is somewhat disappointing, considering the fact that effective disease prevention includes widespread CT screening. Further studies in different settings are needed in order to analyze how the testing rate for CT can be improved in clinical praxis

Variations in color and reflectance on the surface of asteroid (101955) Bennu

Visible-wavelength color and reflectance provide information about the geologic history of planetary surfaces. We present multispectral images (0.44 to 0.89 microns) of near-Earth asteroid (101955) Bennu. The surface has variable colors overlain on a moderately blue global terrain. Two primary boulder types are distinguishable by their reflectance and texture. Space weathering of Bennu surface materials does not simply progress from red to blue (or vice versa). Instead, freshly exposed, redder surfaces initially brighten in the near-ultraviolet (become bluer at shorter wavelengths), then brighten in the visible to near-infrared, leading to Bennu’s moderately blue average color. Craters indicate that the timescale of these color changes is ~105 years. We attribute the reflectance and color variation to a combination of primordial heterogeneity and varying exposure ages

Regulation of Budding Yeast Mating-Type Switching Donor Preference by the FHA Domain of Fkh1

During Saccharomyces cerevisiae mating-type switching, an HO endonuclease-induced double-strand break (DSB) at MAT is repaired by recombining with one of two donors, HMLα or HMRa, located at opposite ends of chromosome III. MATa cells preferentially recombine with HMLα; this decision depends on the Recombination Enhancer (RE), located about 17 kb to the right of HML. In MATα cells, HML is rarely used and RE is bound by the MATα2-Mcm1 corepressor, which prevents the binding of other proteins to RE. In contrast, in MATa cells, RE is bound by multiple copies of Fkh1 and a single copy of Swi4/Swi6. We report here that, when RE is replaced with four LexA operators in MATa cells, 95% of cells use HMR for repair, but expression of a LexA-Fkh1 fusion protein strongly increases HML usage. A LexA-Fkh1 truncation, containing only Fkh1's phosphothreonine-binding FHA domain, restores HML usage to 90%. A LexA-FHA-R80A mutant lacking phosphothreonine binding fails to increase HML usage. The LexA-FHA fusion protein associates with chromatin in a 10-kb interval surrounding the HO cleavage site at MAT, but only after DSB induction. This association occurs even in a donorless strain lacking HML. We propose that the FHA domain of Fkh1 regulates donor preference by physically interacting with phosphorylated threonine residues created on proteins bound near the DSB, thus positioning HML close to the DSB at MAT. Donor preference is independent of Mec1/ATR and Tel1/ATM checkpoint protein kinases but partially depends on casein kinase II. RE stimulates the strand invasion step of interchromosomal recombination even for non-MAT sequences. We also find that when RE binds to the region near the DSB at MATa then Mec1 and Tel1 checkpoint kinases are not only able to phosphorylate histone H2A (γ-H2AX) around the DSB but can also promote γ-H2AX spreading around the RE region

Rad51 Inhibits Translocation Formation by Non-Conservative Homologous Recombination in Saccharomyces cerevisiae

Chromosomal translocations are a primary biological response to ionizing radiation (IR) exposure, and are likely to result from the inappropriate repair of the DNA double-strand breaks (DSBs) that are created. An abundance of repetitive sequences in eukaryotic genomes provides ample opportunity for such breaks to be repaired by homologous recombination (HR) between non-allelic repeats. Interestingly, in the budding yeast, Saccharomyces cerevisiae the central strand exchange protein, Rad51 that is required for DSB repair by gene conversion between unlinked repeats that conserves genomic structure also suppresses translocation formation by several HR mechanisms. In particular, Rad51 suppresses translocation formation by single-strand annealing (SSA), perhaps the most efficient mechanism for translocation formation by HR in both yeast and mammalian cells. Further, the enhanced translocation formation that emerges in the absence of Rad51 displays a distinct pattern of genetic control, suggesting that this occurs by a separate mechanism. Since hypomorphic mutations in RAD51 in mammalian cells also reduce DSB repair by conservative gene conversion and stimulate non-conservative repair by SSA, this mechanism may also operate in humans and, perhaps contribute to the genome instability that propels the development of cancer

Extensive Genetic Diversity, Unique Population Structure and Evidence of Genetic Exchange in the Sexually Transmitted Parasite Trichomonas vaginalis

The human parasite Trichomonas vaginalis causes trichomoniasis, the world's most common non-viral sexually transmitted infection. Research on T. vaginalis genetic diversity has been limited by a lack of appropriate genotyping tools. To address this problem, we recently published a panel of T. vaginalis-specific genetic markers; here we use these markers to genotype isolates collected from ten regions around the globe. We detect high levels of genetic diversity, infer a two-type population structure, identify clinically relevant differences between the two types, and uncover evidence of genetic exchange in what was believed to be a clonal organism. Together, these results greatly improve our understanding of the population genetics of T. vaginalis and provide insights into the possibility of genetic exchange in the parasite, with implications for the epidemiology and control of the disease. By taking into account the existence of different types and their unique characteristics, we can improve understanding of the wide range of symptoms that patients manifest and better implement appropriate drug treatment. In addition, by recognizing the possibility of genetic exchange, we are more equipped to address the growing concern of drug resistance and the mechanisms by which it may spread within parasite populations

Properties of Rubble-Pile Asteroid (101955) Bennu from OSIRIS-REx Imaging and Thermal Analysis

Establishing the abundance and physical properties of regolith and boulders on asteroids is crucial for understanding the formation and degradation mechanisms at work on their surfaces. Using images and thermal data from NASA's Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) spacecraft, we show that asteroid (101955) Bennu's surface is globally rough, dense with boulders, and low in albedo. The number of boulders is surprising given Bennu's moderate thermal inertia, suggesting that simple models linking thermal inertia to particle size do not adequately capture the complexity relating these properties. At the same time, we find evidence for a wide range of particle sizes with distinct albedo characteristics. Our findings imply that ages of Bennu's surface particles span from the disruption of the asteroid's parent body (boulders) to recent in situ production (micrometre-scale particles)