Pulmonary artery pressure monitoring in chronic heart failure: effects across clinically relevant subgroups in the MONITOR-HF trial.

BACKGROUND AND AIMS: In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. METHODS: The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronisation therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life, clinical, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. RESULTS: The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P-values were nonsignificant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (Pinteraction = 0.03; adjusted Pinteraction = 0.33) and diabetics (Pinteraction = 0.01; adjusted Pinteraction = 0.06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. CONCLUSIONS: This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients.

Characteristics and outcomes of COVID-19 in heart transplantation recipients in the Netherlands.

BACKGROUND: Immunocompromised patients are at high risk of complicated severe acute respiratory coronavirus 2 infection. The aim of this retrospective study was to describe the characteristics and outcomes of heart transplantation (HTx) recipients with coronavirus disease 2019 (COVID-19) in the Netherlands. METHODS: HTx patients from one of the three HTx centres in the Netherlands with COVID-19 (proven by positive reverse-transcription polymerase chain reaction or serology test result) between February 2020 and June 2021 were included. The primary endpoint was all-cause mortality and the secondary endpoint was disease severity. RESULTS: COVID-19 was diagnosed in 54/665 HTx patients (8%), with a mean (±â€¯standard deviation (SD)) time after HTx of 11 ± 8 years. Mean (±â€¯SD) age was 53 ± 14 years and 39% were female. Immunosuppressive therapy dosage was reduced in 37% patients (20/54). Hospitalisation was required in 39% patients (21/54), and 13% patients (7/54) had severe COVID-19 (leading to intensive care unit (ICU) admission or death). In-hospital mortality was 14% (3/21), and all-cause mortality was 6%. Compared with patients with moderate COVID-19 (hospitalised without ICU indication), severe COVID-19 patients tended to be transplanted earlier and had a significantly higher mean (±â€¯SD) body mass index (26 ± 3 vs 30 ± 3 kg/m2, p = 0.01). Myocardial infarction, cellular rejection and pulmonary embolism were observed once in three different HTx patients. CONCLUSION: HTx patients were at increased risk of complicated COVID-19 with frequent hospitalisation, but the all-cause mortality was substantially lower than previously described (7-33%).

Extremely metal-poor stars from the cosmic dawn in the bulge of the Milky Way.

The first stars are predicted to have formed within 200 million years after the Big Bang, initiating the cosmic dawn. A true first star has not yet been discovered, although stars with tiny amounts of elements heavier than helium ('metals') have been found in the outer regions ('halo') of the Milky Way. The first stars and their immediate successors should, however, preferentially be found today in the central regions ('bulges') of galaxies, because they formed in the largest over-densities that grew gravitationally with time. The Milky Way bulge underwent a rapid chemical enrichment during the first 1-2 billion years, leading to a dearth of early, metal-poor stars. Here we report observations of extremely metal-poor stars in the Milky Way bulge, including one star with an iron abundance about 10,000 times lower than the solar value without noticeable carbon enhancement. We confirm that most of the metal-poor bulge stars are on tight orbits around the Galactic Centre, rather than being halo stars passing through the bulge, as expected for stars formed at redshifts greater than 15. Their chemical compositions are in general similar to typical halo stars of the same metallicity although intriguing differences exist, including lower abundances of carbon.

An eclipsing-binary distance to the Large Magellanic Cloud accurate to two per cent.

In the era of precision cosmology, it is essential to determine the Hubble constant to an accuracy of three per cent or better. At present, its uncertainty is dominated by the uncertainty in the distance to the Large Magellanic Cloud (LMC), which, being our second-closest galaxy, serves as the best anchor point for the cosmic distance scale. Observations of eclipsing binaries offer a unique opportunity to measure stellar parameters and distances precisely and accurately. The eclipsing-binary method was previously applied to the LMC, but the accuracy of the distance results was lessened by the need to model the bright, early-type systems used in those studies. Here we report determinations of the distances to eight long-period, late-type eclipsing systems in the LMC, composed of cool, giant stars. For these systems, we can accurately measure both the linear and the angular sizes of their components and avoid the most important problems related to the hot, early-type systems. The LMC distance that we derive from these systems (49.97 ± 0.19 (statistical) ± 1.11 (systematic) kiloparsecs) is accurate to 2.2 per cent and provides a firm base for a 3-per-cent determination of the Hubble constant, with prospects for improvement to 2 per cent in the future.

One or more bound planets per Milky Way star from microlensing observations.

Most known extrasolar planets (exoplanets) have been discovered using the radial velocity or transit methods. Both are biased towards planets that are relatively close to their parent stars, and studies find that around 17-30% (refs 4, 5) of solar-like stars host a planet. Gravitational microlensing, on the other hand, probes planets that are further away from their stars. Recently, a population of planets that are unbound or very far from their stars was discovered by microlensing. These planets are at least as numerous as the stars in the Milky Way. Here we report a statistical analysis of microlensing data (gathered in 2002-07) that reveals the fraction of bound planets 0.5-10 AU (Sun-Earth distance) from their stars. We find that 17(+6)(-9)% of stars host Jupiter-mass planets (0.3-10 M(J), where M(J) = 318 M(⊕) and M(⊕) is Earth's mass). Cool Neptunes (10-30 M(⊕)) and super-Earths (5-10 M(⊕)) are even more common: their respective abundances per star are 52(+22)(-29)% and 62(+35)(-37)%. We conclude that stars are orbited by planets as a rule, rather than the exception.

On the mechanism of mechanochemical molecular encapsulation in peptidic capsules.

Molecular encapsulation of C60 inside a hydrogen-bond-sealed semi-flexible peptidic capsule is hindered in solution, yet it proceeds effectively after mechanical milling of a solid sample. We show that the molecular mechanism involves the generation of non-covalently disordered forms that are active in guest uptake. We also show that the solvent-free mechanochemical covalent synthesis of capsules directly results in obtaining disordered, active forms.

Non-paraganglioma tumors of the jugular foramen - Growth patterns, radiological presentation, differential diagnosis.

OBJECTIVE: Most common tumors of the jugular foramen are paragangliomas. However, other lesions, also malignant, may involve the jugular foramen and mimic radiographic presentation of paragangliomas. Therefore, a correct preoperative diagnosis is crucial for best treatment planning. This study analyzes imaging characteristics of non-paraganglioma neoplasms involving the jugular foramen, with attention given to features helpful in differential diagnosis. STUDY DESIGN: A retrospective chart search. SETTING: Teritary referral university centre. SUBJECTS AND METHODS: During the years 1997-2010, 11 cases of jugular foramen tumors other than paragangliomas, with available imaging studies, were identified. Histopathology revealed: 3 schwannomas, 1 malignant schwannoma, 2 meningiomas, 1 hemangiopericytoma, 1 ependymoma, 1 endolymphatic sac carcinoma (ELST) and 2 nasopharyngeal carcinoma metastases. CT, MRI and angiography were assessed to determine tumor growth directions, bone involvement, tumor morphology and vascular composition. RESULTS: Schwannomas were characterized by parapharyngeal space involvement, jugular foramen expansion, preservation of cortical margins, irregular contrast enhancement. Meningiomas presented diffuse bone infiltration, sclerotic changes, erosion of the cortical bone. Ependymoma showed diffuse skull base infiltration, permeative erosion, heterogeneity, abundant vascularization. Hemangiopericytoma radiologically imitated paraganglioma. ELST showed permeative/geographic bony destruction, heterogeneity, intratumoral bony fragments. Metastases were lytic, solid lesions characterized by circumferential growth, internal carotid artery encasement and stenosis. CONCLUSIONS: A combination of certain radiological features including tumor epicenter, growth vectors, skull base infiltration, bony changes and tumor morphology help establish correct preoperative diagnosis and differentiate less common jugular foramen tumors, from most common paragangliomas. Hemangiopericytoma may radiologically mimic paraganglioma.

Fiber Bragg gratings in hole-assisted multicore fiber for space division multiplexing.

In this Letter we present, for the first time to our knowledge, the results of fiber Bragg grating (FBG) inscription in a novel microstructured multicore fiber characterized by seven single-mode isolated cores. A clear Bragg reflection peak can be observed in all of the 7 cores after one inscription process with a KrF nanosecond laser in a Talbot interferometer set up. We furthermore perform a numerical analysis of the effective refractive indices of the particular modes and compare it with the FBG inscription results. An experimental analysis of the strain and temperature sensitivities of all of the Bragg peaks is also included.

Increased cardiovascular risk in rats with primary renal dysfunction; mediating role for vascular endothelial function.

Primary chronic kidney disease is associated with high cardiovascular risk. However, the exact mechanisms behind this cardiorenal interaction remain unclear. We investigated the interaction between heart and kidneys in novel animal model for cardiorenal interaction. Normal Wistar rats and Munich Wistar Fromter rats, spontaneously developing renal dysfunction, were subjected to experimental myocardial infarction to induce cardiac dysfunction (CD) and combined cardiorenal dysfunction (CRD), respectively (N = 5-10). Twelve weeks later, cardiac- and renal parameters were evaluated. Cardiac, but not renal dysfunction was exaggerated in CRD. Accelerated cardiac dysfunction in CRD was indicated by decreased cardiac output (CD 109 ± 10 vs. CRD 79 ± 8 ml/min), diastolic dysfunction (E/e') (CD 26 ± 2 vs. CRD 50 ± 5) and left ventricular overload (LVEDP CD 10.8 ± 2.8 vs. CRD 21.6 ± 1.7 mmHg). Congestion in CRD was confirmed by increased lung and atrial weights, as well as exaggerated right ventricular hypertrophy. Absence of accelerated renal dysfunction, measured by increased proteinuria, was supported by absence of additional focal glomerulosclerosis or further decline of renal blood flow in CRD. Only advanced peripheral endothelial dysfunction, as found in CRD, appeared to correlate with both renal and cardiac dysfunction parameters. Thus, proteinuric rats with myocardial infarction showed accelerated cardiac but not renal dysfunction. As parameters mimic the cardiorenal syndrome, these rats may provide a clinically relevant model to study increased cardiovascular risk due to renal dysfunction. Peripheral endothelial dysfunction was the only parameter that correlated with both renal and cardiac dysfunction, which may indicate a mediating role in cardiorenal interaction.

Discovery of a cool planet of 5.5 Earth masses through gravitational microlensing.

In the favoured core-accretion model of formation of planetary systems, solid planetesimals accumulate to build up planetary cores, which then accrete nebular gas if they are sufficiently massive. Around M-dwarf stars (the most common stars in our Galaxy), this model favours the formation of Earth-mass (M(o)) to Neptune-mass planets with orbital radii of 1 to 10 astronomical units (au), which is consistent with the small number of gas giant planets known to orbit M-dwarf host stars. More than 170 extrasolar planets have been discovered with a wide range of masses and orbital periods, but planets of Neptune's mass or less have not hitherto been detected at separations of more than 0.15 au from normal stars. Here we report the discovery of a 5.5(+5.5)(-2.7) M(o) planetary companion at a separation of 2.6+1.5-0.6 au from a 0.22+0.21-0.11 M(o) M-dwarf star, where M(o) refers to a solar mass. (We propose to name it OGLE-2005-BLG-390Lb, indicating a planetary mass companion to the lens star of the microlensing event.) The mass is lower than that of GJ876d (ref. 5), although the error bars overlap. Our detection suggests that such cool, sub-Neptune-mass planets may be more common than gas giant planets, as predicted by the core accretion theory.

Associations between bovine, human, and raw milk, and beef isolates of non-O157 Shiga toxigenic Escherichia coli within a restricted geographic area of the United States.

A survey for Shiga toxigenic Escherichia coli in raw milk and beef was conducted within a defined geographic region of the United States. Prevalence rates based on detection of Shiga toxin gene (stx) were 36% for retail beef, 23% for beef carcasses, and 21% for raw milk samples, which were significantly higher than were Shiga toxigenic E. coli isolation rates of 7.5, 5.8, and 3.2%, respectively. Seasonal prevalence differences were significant for stx positivity among ground beef and milk samples. Distribution of stx subtypes among isolates varied according to sample type, with stx1 predominating in milk, stx2 on carcasses, and the combination of both stx1 and stx2 in beef. Ancillary virulence markers eae and ehx were evident in 23 and 15% of isolates, respectively. Pulsed-field gel electrophoresis demonstrated associations between food isolates and sympatric bovine fecal, and human clinical isolates. These data demonstrate that non-O157 Shiga toxigenic E. coli is present in the food chain in the Pacific Northwest, and its risk to health warrants critical assessment.

A chiral member of the family of organic hexameric cages.

A cubic nanocage (O symmetry) that exhibits inherent chirality and has a covalent, rigid skeleton with molecule-sized entrance portals was obtained by means of dynamic covalent chemistry using a reaction between aldehyde-functionalized resorcin[4]arene and hydrazine.

Regulatory RNAs in mammals.

Recent years have brought a dramatic change in our understanding of the role of ribonucleic acids (RNAs) within the cell. In addition to the already well-known classes of RNAs that take part in the transmission of genetic information from DNA to proteins, a new highly heterogeneous group of RNA molecules has emerged. The regulatory nonprotein-coding RNAs (npcRNAs) have been shown to be involved in modulation of gene expression on both the transcriptional and post-transcriptional level. They participate in mechanisms of chromatin modification, regulation of transcription factor activity, and influencing mRNA stability, processing, and translation. npcRNAs are key factors in genetic imprinting, dosage compensation of X-chromosome-linked genes, and many processes of differentiation and development.

Aminoacyl-tRNA synthetases database.

Aminoacyl-tRNA synthetases (AARSs) are at the center of the question of the origin of life. They constitute a family of enzymes integrating the two levels of cellular organization: nucleic acids and proteins. AARSs arose early in evolution and are believed to be a group of ancient proteins. They are responsible for attaching amino acid residues to their cognate tRNA molecules, which is the first step in the protein synthesis. The role they play in a living cell is essential for the precise deciphering of the genetic code. The analysis of AARSs evolutionary history was not possible for a long time due to a lack of a sufficiently large number of their amino acid sequences. The emerging picture of synthetases' evolution is a result of recent achievements in genomics [Woese,C., Olsen,G.J., Ibba,M. and Söll,D. (2000) Microbiol. Mol. Biol. Rev., 64, 202-236]. In this paper we present a short introduction to the AARSs database. The updated database contains 1047 AARS primary structures from archaebacteria, eubacteria, mitochondria, chloroplasts and eukaryotic cells. It is the compilation of amino acid sequences of all AARSs known to date, which are available as separate entries via the WWW at http://biobases.ibch.poznan.pl/aars/.

The non-coding RNAs as riboregulators.

The non-coding RNAs database (http://biobases.ibch.poznan.pl/ncRNA/) contains currently available data on RNAs, which do not have long open reading frames and act as riboregulators. Non-coding RNAs are involved in the specific recognition of cellular nucleic acid targets through complementary base pairing to control cell growth and differentiation. Some of them are connected with several well known developmental and neuro-behavioral disorders. We have divided them into four groups. This paper is a short introduction to the database and presents its latest, updated edition.

The frequency of snowline-region planets from four-years of OGLE-MOA-Wise second-generation microlensing.

We present a statistical analysis of the first four seasons from a "second-generation" microlensing survey for extrasolar planets, consisting of near-continuous time coverage of 8 deg2 of the Galactic bulge by the OGLE, MOA, and Wise microlensing surveys. During this period, 224 microlensing events were observed by all three groups. Over 12% of the events showed a deviation from single-lens microlensing, and for ~1/3 of those the anomaly is likely caused by a planetary companion. For each of the 224 events we have performed numerical ray-tracing simulations to calculate the detection efficiency of possible companions as a function of companion-to-host mass ratio and separation. Accounting for the detection efficiency, we find that 55 - 22 + 34 % of microlensed stars host a snowline planet. Moreover, we find that Neptunes-mass planets are ~ 10 times more common than Jupiter-mass planets. The companion-to-host mass ratio distribution shows a deficit at q ~ 10-2, separating the distribution into two companion populations, analogous to the stellar-companion and planet populations, seen in radial-velocity surveys around solar-like stars. Our survey, however, which probes mainly lower-mass stars, suggests a minimum in the distribution in the super-Jupiter mass range, and a relatively high occurrence of brown-dwarf companions.

The nucleotide sequence of 5S ribosomal RNA from the parasitic nematode Ascaris suum. Evolutionary relationships in nematodes.

We have determined the nucleotide sequence of 5S ribosomal RNA from the parasitic nematode Ascaris suum. The analysis of all Nematoda 5S rRNAs and their genes shows that this group must have diverged from other Metazoa at early stages of evolution. This conclusion is supported by the sequence variability in single-stranded regions which are strongly conserved in animal 5S rRNAs.

Compilation of ribosomal 5S ribonucleic acid nucleotide sequences: eukaryotic 5S rRNAs.

5S Ribosomal RNA is the smallest RNA component of the ribosomes. Due to relatively simple isolation and sequencing procedures as well as a potential use of the sequence data in evolutionary analyses, the amount of known nucleotide sequences on both RNA and DNA levels was rapidly growing. In this paper we present the updated (March 1996) compilation of eukaryotic 5D rRNA and 5S rDNA sequences.

High lineage diversity and host sharing of malarial parasites in a local avian assemblage.

Bird populations often have high prevalences of the haemosporidians Haemoproteus spp. and Plasmodium spp., but the extent of host sharing and host switching among these parasite lineages and their avian hosts is not well known. While sampling within a small geographic region in which host individuals are likely to have been exposed to the same potential parasite lineages, we surveyed highly variable mitochondrial DNA from haemosporidians isolated from 14 host taxa representing 4 avian families (Hirundinidae, Parulidae, Emberizidae, and Fringillidae). Analyses of cytochrome b sequences from 83 independent infections identified 29 unique haplotypes, representing 2 well-differentiated Haemoproteus spp. lineages and 6 differentiated Plasmodium spp. lineages. A phylogenetic reconstruction of relationships among these lineages provided evidence against host specificity at the species and family levels, as all haemosporidian lineages recovered from 2 or more host individuals (2 Haemoproteus and 3 Plasmodium lineages) were found in at least 2 host families. We detected a similar high level of host sharing; the 3 most intensively sampled host species each harbored 4 highly differentiated haemosporidian lineages. These results indicate that some Haemoproteus spp. and Plasmodium spp. lineages exhibit a low degree of host specificity, a phenomenon with implications for ecological and evolutionary interactions among these parasites and their hosts.

Preparation of HIV TAR RNA with RNA scissors.

Two hammerhead ribozymes derived from plant pathogenic RNAs were used to cut off the HIV TAR RNA from the T7 RNA transcript through a cis cleavage reaction. Stem I of the (+)vLTSV ribozyme comprises 8 nucleotides of the 5' terminus of TAR RNA, but stem III of the (+)sTRSV ribozyme consists of 8 nucleotides of the 3' end of TAR RNA. The construct containing two GUC hammerhead ribozyme target sequences identified the cleavage sites to cut off a required RNA molecule. This method was applied for preparation of 35 nt long TAR RNA. Its activity was proved by the complex formation with the Tat protein. It seems that this approach based on RNA scissors can also be used for the generation of required RNA molecules, RNA decoys or RNA aptamers in vivo.