Bacterial behavior on coated porous titanium substrates for biomedical applications

In this work, bacterial behavior on dense and porous titanium substrates is discussed. Porous titanium was fabricated by a space holder technique using 50 vol , NH4HCO3 with particle sizes between 250 and 355 amp; 956;m . These substrates were coated by sulfonated PEEK termed SPEEK . Characterization of the porous substrate was carried out using the Archimedes Method, Image Analysis, and three dimensional X ray Micro Computed Tomography including total and interconnected porosity, equivalent diameter, and pore shape factor , as well as mechanical characterization specifically stiffness and yield strength . A detailed study was performed here to investigate the influence of substrate porosity on the adhesion and proliferation of E. coli, MRSA, and P. aeruginosa common causes of orthopedic device associated infections . Bacterial colonization was examined in terms of the initial bacterial concentration, as well as bacterial adherence to and growth on the surface and inside the pores. Results suggest that fully dense titanium supported the least bacterial colonization, while the porous titanium promoted bacterial growth in the medium and inside the cavities. Furthermore, the SPEEK coating deposited onto the samples inhibited bacteria growth inside the porous materials. In this manner, this study showed for the first time that SPEEK could have potential antibacterial properties to offset the increase in bacteria growth commonly observed in porous material

GMASS Ultradeep Spectroscopy of Galaxies at 1.4<z<2. II. Superdense passive galaxies: how did they form and evolve ?

We combine ultradeep optical spectroscopy from the GMASS project ("Galaxy Mass Assembly ultradeep Spectroscopic Survey") with GOODS multi-band photometry and HST imaging to study a sample of passive galaxiesat 1.39<z<1.99 selected at 4.5 microns. A stacked spectrum with an equivalent integration time of ~500 hours was obtained is publicly released. The spectral and photometric SED properties indicate very weak or absent star formation, moderately old stellar ages of ~1 Gyr (for solar metallicity) and stellar masses in the range of 10^{10-11} solar masses, thus implying that the major star formation and assembly processes for these galaxies occurred at z>2. These galaxies have morphologies that are predominantly compact and spheroidal.However, their sizes (R_e <~ 1 kpc) are much smaller than those of spheroids in the present--day Universe. Their stellar mass surface densities are consequently higher by ~1 dex if compared to spheroids at z~0 with the same mass. Their rest-frame B-band surface brightness scales with the effective radius, but the offset with respect to the surface brightness of the local Kormendy relation is too large to be explained by simple passive evolution. At z~1, a larger fraction of passive galaxies follows the z~0 size -- mass relation. Superdense relics with R_e~1 kpc are extremely rare at z~0 with respect to z>1, and absent if R_e<1 kpc. Because of the similar sizes and mass densities, we suggest that the superdense passive galaxies at 1<z<2 are the remnants of the powerful starbursts occurring in submillimeter--selected galaxies at z>2. The results are compared with theoretical models and the main implications discussed in the framework of massive galaxy formation and evolution.Comment: 22 pages, 23 figures, Astronomy & Astrophysics, in pres

LEMUR: Large European Module for solar Ultraviolet Research. European contribution to JAXA's Solar-C mission

Understanding the solar outer atmosphere requires concerted, simultaneous solar observations from the visible to the vacuum ultraviolet (VUV) and soft X-rays, at high spatial resolution (between 0.1" and 0.3"), at high temporal resolution (on the order of 10 s, i.e., the time scale of chromospheric dynamics), with a wide temperature coverage (0.01 MK to 20 MK, from the chromosphere to the flaring corona), and the capability of measuring magnetic fields through spectropolarimetry at visible and near-infrared wavelengths. Simultaneous spectroscopic measurements sampling the entire temperature range are particularly important. These requirements are fulfilled by the Japanese Solar-C mission (Plan B), composed of a spacecraft in a geosynchronous orbit with a payload providing a significant improvement of imaging and spectropolarimetric capabilities in the UV, visible, and near-infrared with respect to what is available today and foreseen in the near future. The Large European Module for solar Ultraviolet Research (LEMUR), described in this paper, is a large VUV telescope feeding a scientific payload of high-resolution imaging spectrographs and cameras. LEMUR consists of two major components: a VUV solar telescope with a 30 cm diameter mirror and a focal length of 3.6 m, and a focal-plane package composed of VUV spectrometers covering six carefully chosen wavelength ranges between 17 and 127 nm. The LEMUR slit covers 280" on the Sun with 0.14" per pixel sampling. In addition, LEMUR is capable of measuring mass flows velocities (line shifts) down to 2 km/s or better. LEMUR has been proposed to ESA as the European contribution to the Solar C mission.Comment: 35 pages, 14 figures. To appear on Experimental Astronom

DNA Methylation-Independent Reversion of Gemcitabine Resistance by Hydralazine in Cervical Cancer Cells

BACKGROUND: Down regulation of genes coding for nucleoside transporters and drug metabolism responsible for uptake and metabolic activation of the nucleoside gemcitabine is related with acquired tumor resistance against this agent. Hydralazine has been shown to reverse doxorubicin resistance in a model of breast cancer. Here we wanted to investigate whether epigenetic mechanisms are responsible for acquiring resistance to gemcitabine and if hydralazine could restore gemcitabine sensitivity in cervical cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The cervical cancer cell line CaLo cell line was cultured in the presence of increasing concentrations of gemcitabine. Down-regulation of hENT1 & dCK genes was observed in the resistant cells (CaLoGR) which was not associated with promoter methylation. Treatment with hydralazine reversed gemcitabine resistance and led to hENT1 and dCK gene reactivation in a DNA promoter methylation-independent manner. No changes in HDAC total activity nor in H3 and H4 acetylation at these promoters were observed. ChIP analysis showed H3K9m2 at hENT1 and dCK gene promoters which correlated with hyper-expression of G9A histone methyltransferase at RNA and protein level in the resistant cells. Hydralazine inhibited G9A methyltransferase activity in vitro and depletion of the G9A gene by iRNA restored gemcitabine sensitivity. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that acquired gemcitabine resistance is associated with DNA promoter methylation-independent hENT1 and dCK gene down-regulation and hyper-expression of G9A methyltransferase. Hydralazine reverts gemcitabine resistance in cervical cancer cells via inhibition of G9A histone methyltransferase

Utilization of mechanical power and associations with clinical outcomes in brain injured patients. a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

BackgroundThere is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes.MethodsIn this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale &lt;= 12 before intubation) who required mechanical ventilation (MV) &gt;= 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS).ResultsWe included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22).ConclusionsExposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network

Objectives In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.Conclusions Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required

Measurement of Energy Correlators inside Jets and Determination of the Strong Coupling Formula Presented

Energy correlators that describe energy-weighted distances between two or three particles in a hadronic jet are measured using an event sample of $\sqrt{s}$=13 TeV proton-proton collisions collected by the CMS experiment and corresponding to an integrated luminosity of 36.3 fb$^{−1}$. The measured distributions are consistent with the trends in the simulation that reveal two key features of the strong interaction: confinement and asymptotic freedom. By comparing the ratio of the measured three- and two-particle energy correlator distributions with theoretical calculations that resum collinear emissions at approximate next-to-next-to-leading-logarithmic accuracy matched to a next-to-leading-order calculation, the strong coupling is determined at the Z boson mass: α$_S$ (m$_Z$)=0.1229 $\frac{0.0040}{-0.0050}$ , the most precise α$_S$m$_Z$ value obtained using jet substructure observable

Search for heavy neutral leptons in final states with electrons, muons, and hadronically decaying tau leptons in proton-proton collisions at s \sqrt{s} = 13 TeV

A search for heavy neutral leptons (HNLs) of Majorana or Dirac type using proton-proton collision data at = 13 TeV is presented. The data were collected by the CMS experiment at the CERN LHC and correspond to an integrated luminosity of 138 fb−1. Events with three charged leptons (electrons, muons, and hadronically decaying tau leptons) are selected, corresponding to HNL production in association with a charged lepton and decay of the HNL to two charged leptons and a standard model (SM) neutrino. The search is performed for HNL masses between 10 GeV and 1.5 TeV. No evidence for an HNL signal is observed in data. Upper limits at 95% confidence level are found for the squared coupling strength of the HNL to SM neutrinos, considering exclusive coupling of the HNL to a single SM neutrino generation, for both Majorana and Dirac HNLs. The limits exceed previously achieved experimental constraints for a wide range of HNL masses, and the limits on tau neutrino coupling scenarios with HNL masses above the W boson mass are presented for the first time