ATP-evoked intracellular Ca2+ responses in M-CSF differentiated human monocyte-derived macrophage are mediated by P2X4 and P2Y11 receptor activation

Tissues differentially secrete multiple colony stimulating factors under conditions of homeostasis and inflammation, orientating recruited circulating monocytes to differentiate to macrophage with differing functional phenotypes. Here, we investigated ATP-evoked intracellular Ca2+ responses in human macrophage differentiated with macrophage colony-stimulating factor (M-CSF). Extracellular ATP evoked (EC50 13.3 ± 1.4 µM) robust biphasic intracellular Ca2+ responses that showed a dependency on both metabotropic (P2Y) and ionotropic (P2X) receptors. qRT-PCR and immunocytochemistry revealed the expression of P2Y1, P2Y2, P2Y6, P2Y11, P2Y13, P2X1, P2X4, P2X5, and P2X7. Pharmacological analysis revealed contribution of only P2X4 and P2Y11 to the Ca2+ response evoked by maximal ATP concentrations (100 µM). This study reveals the contribution of P2X4 and P2Y11 receptor activation to ATP-evoked intracellular Ca2+ responses, and makes comparison with macrophage differentiated using granulocyte colony-stimulating factor (GM-CSF)

The use of medicaments in the management of symptomatic irreversible pulpitis: a community-based cohort study

Aim: To investigate patient outcomes from either pulpotomy or pulpectomy for the management of symptomatic irreversible pulpitis, with and without application of antibiotic/corticosteroid pastes in urgent primary dental care settings in the United Kingdom. Methodology: All patients receiving intervention for symptomatic irreversible pulpitis in three different primary care settings were invited to participate. Pre-operatively, data regarding patients’ numerical ratings scale (NRS), pain score (0-10), analgesic use, oral-health impact profile-14 (OHIP-14) and need for time away from work were collected. For seven days post operatively, participants recorded their NRS pain score, global rating of change score, medication use and their ability to work. Analysis used a mixed-effects model with post-hoc Tukey’s multiple comparisons test for continuous data and chi-squared or Fisher\ub4s exact test for categorical data. To test the effect of the corticosteroid/antibiotic paste, pulpectomy and pulpotomy groups were combined following Mantel-Haenszel stratified analysis or a weighted average of the difference between pulpotomy and pulpectomy with and without the use of corticosteroid/antibiotic paste. A binary composite score was constructed using pre- and post-operative data, whereby overall treatment success was defined as: i. patients did not return for treatment due to pain by day seven; ii. at day three there was a 33% (or 2-points) reduction in NRS pain score; iii. there was a change score of +3 in global rating; iv. the patient was no-longer using analgesia and able to return to work. Results Eighty-five participants were recruited, with 83 completing follow-up. Overall treatment success was 57%, with 25% of participants returning for more treatment due to inadequate pain relief. Overall treatment success did not differ between the two groups (p=0.645), although patients self-reported greater improvement with an antibiotic/corticosteroid dressing for global rating of change (p=0.015). Conclusions: This study identified limited evidence of improved outcomes using antibiotic/corticosteroid dressings in the management of symptomatic irreversible pulpitis in the emergency setting. Further clinical research is needed to understand if these medications are beneficial in affording pain relief, above that of simple excision of irreversibly inflamed pulp tissue. Funding This study was funded by the European Society of Endodontology Young Investigator Grant (2020). Conflict of interest None to declare

Circular polarization survey of intermediate polars I. Northern targets in the range 17h<R.A.<23h

Context. The origin, evolution, and ultimate fate of magnetic cataclysmic variables are poorly understood. It is largely the nature of the magnetic fields in these systems that leads to this poor understanding. Fundamental properties, such as the field strength and the axis alignment, are unknown in a majority of these systems. Aims. We undertake to put all the previous circular polarization measurements into context and systematically survey intermediate polars for signs of circular polarization, hence to get an indication of their true magnetic field strengths and try to understand the evolution of magnetic cataclysmic variables. Methods. We used the TurPol instrument at the Nordic Optical Telescope to obtain simultaneous UBVRI photo-polarimetric observations of a set of intermediate polars, during the epoch 2006 July 31 - August 2. Results. Of this set of eight systems two (1RXS J213344.1+510725 and 1RXS J173021.5-055933) were found to show significant levels of circular polarization, varying with spin phase. Five others (V2306 Cyg, AO Psc, DQ Her, FO Aqr, and V1223 Sgr) show some evidence for circular polarization and variation of this with spin phase, whilst AE Aqr shows little evidence for polarized emission. We also report the first simultaneous UBVRI photometry of the newly identified intermediate polar 1RXS J173021.5-055933. Conclusions. Circular polarization may be ubiquitous in intermediate polars, albeit at a low level of one or two percent or less. It is stronger at longer wavelengths in the visible spectrum. Our results lend further support to the possible link between the presence of soft X-ray components and the detectability of circular polarization in intermediate polars.Comment: 14 pages. Accepted for publication in A&

European regulatory agenices should employ full time statisticians

No abstract available

Broad-band properties of the hard X-ray cataclysmic variables IGR J00234+6141 and 1RXS J213344.1+510725

A significant number of cataclysmic variables were detected as hard X-ray sources in the INTEGRAL survey, most of them of the magnetic intermediate polar type. We present a detailed X-ray broad-band study of two new sources, IGR J00234+6141 and 1RXS J213344.1+510725, that allow us to classify them as secure members of the intermediate polar class. Timing and spectral analysis of IGR J00234+6141 are based on a XMM-Newton observation and INTEGRAL publicly available data. For 1RXS J213344.1+510725 we use XMM-Newton and Suzaku observations at different epochs, as well as INTEGRAL publicly available data. We determine a spin period of 561.64 +/- 0.56 s for the white dwarf in IGR J00234+6141. The X-ray pulses are observed up to about 2 keV. From XMM-Newton and Suzaku observations of 1RXS J213344.1+510725, we find a rotational period of 570.862 +/- 0.034 s. The observations span three epochs where the pulsation is observed to change at different energies both in amplitude and shape. In both objects, the spectral analysis spanned over a wide energy range, from 0.3 to 100 keV, shows the presence of multiple emission components absorbed by dense material. The X-ray spectrum of IGR J00234+6141 is consistent with a multi-temperature plasma with a maximum temperature of about 50 keV. In 1RXS J213344.1+510725, multiple optically thin components are inferred, as well as an optically thick (blackbody) soft X-ray emission with a temperature of about 100 eV. This latter adds 1RXS J213344.1+510725 to the growing group of soft X-ray intermediate polars. (abridged)Comment: 12 pages, 8 figures, 5 tables. Accepted for publication in A&

Factors predicting treatment of World Trade Center-related lung injury : a longitudinal cohort study

The factors that predict treatment of lung injury in occupational cohorts are poorly defined. We aimed to identify patient characteristics associated with initiation of treatment with inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) >2 years among World Trade Center (WTC)-exposed firefighters. The study population included 8530 WTC-exposed firefighters. Multivariable logistic regression assessed the association of patient characteristics with ICS/LABA treatment for >2 years over two-year intervals from 11 September 2001-10 September 2017. Cox proportional hazards models measured the association of high probability of ICS/LABA initiation with actual ICS/LABA initiation in subsequent intervals. Between 11 September 2001-1 July 2018, 1629/8530 (19.1%) firefighters initiated ICS/LABA treatment for >2 years. Forced Expiratory Volume in 1 s (FEV1), wheeze, and dyspnea were consistently and independently associated with ICS/LABA treatment. High-intensity WTC exposure was associated with ICS/LABA between 11 September 2001-10 September 2003. The 10th percentile of risk for ICS/LABA between 11 September 2005-10 Septmeber 2007 was associated with a 3.32-fold increased hazard of actual ICS/LABA initiation in the subsequent 4 years. In firefighters with WTC exposure, FEV1, wheeze, and dyspnea were independently associated with prolonged ICS/LABA treatment. A high risk for treatment was identifiable from routine monitoring exam results years before treatment initiation

The significance of the time interval between antecedent pregnancy and diagnosis of high-risk gestational trophoblastic tumours

It is thought that the time interval between the antecedent pregnancy and diagnosis of gestational trophoblastic tumours (GTTs) may influence the outcome of these patients. In this study, we investigate the significance of this time interval. Multivariate analysis was used to investigate if the time interval was of prognostic significance from our cohort of 241 high-risk patients with GTT. Subsequent cutpoint analysis was used to determine an optimal cutpoint for the interval covariate. The outcome of these patients was plotted according to the Kaplan–Meier method. The time interval was of prognostic significance on multivariate analysis. A period of greater than 2.8 years after pregnancy was found to be of most significance. The 5-year overall survival was 62.0% (95% CI: 47–76%) for greater than 2.8 years vs 94% (95% CI: 91–97%) for less than 2.8 years (P<0.001). Multivariate analysis showed the presence of liver metastasis and the number of metastasis was also of prognostic importance. The interval between antecedent pregnancy and diagnosis in high-risk GTT is of prognostic significance. This gives some insight into the pathogenesis of the disease

Ancestral Components of Admixed Genomes in a Mexican Cohort

For most of the world, human genome structure at a population level is shaped by interplay between ancient geographic isolation and more recent demographic shifts, factors that are captured by the concepts of biogeographic ancestry and admixture, respectively. The ancestry of non-admixed individuals can often be traced to a specific population in a precise region, but current approaches for studying admixed individuals generally yield coarse information in which genome ancestry proportions are identified according to continent of origin. Here we introduce a new analytic strategy for this problem that allows fine-grained characterization of admixed individuals with respect to both geographic and genomic coordinates. Ancestry segments from different continents, identified with a probabilistic model, are used to construct and study “virtual genomes” of admixed individuals. We apply this approach to a cohort of 492 parent–offspring trios from Mexico City. The relative contributions from the three continental-level ancestral populations—Africa, Europe, and America—vary substantially between individuals, and the distribution of haplotype block length suggests an admixing time of 10–15 generations. The European and Indigenous American virtual genomes of each Mexican individual can be traced to precise regions within each continent, and they reveal a gradient of Amerindian ancestry between indigenous people of southwestern Mexico and Mayans of the Yucatan Peninsula. This contrasts sharply with the African roots of African Americans, which have been characterized by a uniform mixing of multiple West African populations. We also use the virtual European and Indigenous American genomes to search for the signatures of selection in the ancestral populations, and we identify previously known targets of selection in other populations, as well as new candidate loci. The ability to infer precise ancestral components of admixed genomes will facilitate studies of disease-related phenotypes and will allow new insight into the adaptive and demographic history of indigenous people