Identification of Predictive Markers of Response to Immunomodulators in the Treatment of COVID-19 Patients.

BACKGROUND: Proper identification of patients at risk of developing serious disease in the context of SARS-CoV-2 infection, as well as the initiation of early treatment, is one of the fundamental elements for successful management of COVID-19. The main objective of this study was to evaluate the usefulness of serum biomarkers (neutrophils, lymphocytes, C-reactive protein, lactate dehydrogenase, D-dimer, ferritin, and interleukin-6) to predict the early response to immunosuppressant therapy in COVID-19 patients. METHODS: This is a case-control study nested in a retrospective cohort, which included hospitalized patients with interstitial pneumonia and with elevation of some proinflammatory parameters. Each of the individuals who died during the 28-day follow-up was defined as a case. For each case, 4 controls were selected, matched by age, gender, and comorbidities. RESULTS: The initial cohort included 856 patients. The incidence of therapeutic failure in the cohort was 14%, thus we identified a total of 120 cases. After the application of a Cox regression model, high serum concentrations of LDH (> 451 IU/L), ferritin (> 1,014 ng/mL) and D-Dimer (> 1,300 ng/mL) were identified as predictors of poor response to treatment. Highly-specific cut-off points could not be established for any of these biomarkers. CONCLUSIONS: Some inflammatory biomarkers, such as LDH, ferritin, and D-dimer, may be helpful in identifying patients for whom an early immunomodulatory therapeutic intervention should be considered in the treatment of COVID-19 patients with pneumonia.

Influence of H2S on the pitting corrosion of 316L stainless steel in oilfield brine.

Coupon immersion tests were performed on 316L stainless steel in a simulated oilfield environment to evaluate the effect of H2S partial pressure on pit depth and density. Pitting was most significant at intermediate partial pressures of H2S, for which free H2S in the pit solution is maximised. Inhibition of pitting at higher partial pressures is attributed to blocking of the pit surface by metal sulphide phases. The key role of pH in the pit solution is to determine the solubility of metal sulphides and the availability of free H2S to adsorb on the reacting pit surface and sustain activity.

Intensity warping for multisite MRI harmonization.

In multisite neuroimaging studies there is often unwanted technical variation across scanners and sites. These "scanner effects" can hinder detection of biological features of interest, produce inconsistent results, and lead to spurious associations. We propose mica (multisite image harmonization by cumulative distribution function alignment), a tool to harmonize images taken on different scanners by identifying and removing within-subject scanner effects. Our goals in the present study were to (1) establish a method that removes scanner effects by leveraging multiple scans collected on the same subject, and, building on this, (2) develop a technique to quantify scanner effects in large multisite studies so these can be reduced as a preprocessing step. We illustrate scanner effects in a brain MRI study in which the same subject was measured twice on seven scanners, and assess our method's performance in a second study in which ten subjects were scanned on two machines. We found that unharmonized images were highly variable across site and scanner type, and our method effectively removed this variability by aligning intensity distributions. We further studied the ability to predict image harmonization results for a scan taken on an existing subject at a new site using cross-validation.

Unification of hydrogen-enhanced damage understanding through strain-life experiments for modeling.

Strain-life testing of a 4130 pressure vessel steel was conducted in hydrogen gas through the careful adaptation of an existing hydrogen-gas mechanical-testing apparatus. The strain-life mechanical results reveal that hydrogen has a significant effect on the strain-life, and impacts both the elastic and plastic responses of the material. Microscopy analysis shows a distinct difference in the microstructural development of the material after cyclic loading in air compared to after loading in hydrogen gas. These experimental results will inform coupled damage and deformation modeling.

Genes differentially expressed by methylprednisolone in vivo in CD4 T lymphocytes from multiple sclerosis patients: potential biomarkers.

Intravenous methylprednisolone (IVMP) is the gold standard treatment in acute relapses of multiple sclerosis. Knowing the response to IVMP in advance could facilitate earlier selection of patients for subsequent courses of therapy. However, molecular mechanisms and changes in gene expression induced by methylprednisolone remain unknown. The aim of the study was to identify in vivo differentially expressed genes in relapsing-remitting multiple sclerosis patients after 3-6 days of treatment with IVMP. For this purpose, whole-genome transcription profiling of CD4+ T lymphocytes was performed before and after treatment with IVMP in 8 relapsing-remitting multiple sclerosis patients during relapse using Human GE 4x44K v2 microarrays. Differentially expressed genes were identified using a paired t test on GeneSpring v13.0 software. A P-value <0.001 and a twofold change were considered significant. Microarray data were confirmed using real-time PCR. Microarray revealed changes in gene expression: four genes were downregulated (B3GNT3, ZNF683, IFNG and TNF) and seven upregulated (DEFA4, CTSG, DEFA8P, AZU1, MPO, ELANE and PRTN3). Pathway analysis revealed the transforming growth factor-ß signaling pathway to be affected. Comparison with previously published data on in vitro methylprednisolone-regulated genes showed that SMAD7, TNF and CHI3L1 were also downregulated in vivo in relapsing-remitting multiple sclerosis patients. In summary, we performed the first in vivo transcriptome analysis in CD4+ T lymphocytes before and after the treatment with IVMP in patients with multiple sclerosis. Identification of differentially expressed genes in patients receiving IVMP could improve our understanding of the molecular mechanisms underlying the therapeutic effects of IVMP and highlight potential biomarkers of the response to IVMP.

Endocarditis caused by Neisseria bacilliformis: a case report and review of literature.

A 58-years-old male with history of previous aortic prosthetic endocarditis caused by Enterococcus faecalis was admitted due to dyspnoea and fever. The two sets of blood cultures were positive for Neisseria bacilliformis. Transoesophageal echocardiography did not demonstrate endocarditis signs, but PET-CT scan showed active infection signs in the valvular aortic tube and possible infection in the aortic prosthetic valve. A six-week course of ampicillin was prescribed; gentamicin was added during the first two weeks. The patient continued a favourable clinical course. This is the 3rd described case of N. bacilliformis endocarditis and the first one in a prosthetic valve.

Modification to a testing assembly to enable strain-life measurements in pressurized hydrogen gas.

Strain-controlled fully reversed fatigue testing, or strain-life testing, provides critical information on material lifetime and damage response. Strain-life data in hydrogen gas environments is missing in the literature and could provide valuable insights into hydrogen effects on the mechanical response of metals such as steel. We adapted existing hydrogen-gas-environment mechanical-testing equipment, which had been designed only for tensile loads, to accommodate the large compressive loads needed to perform strain-life testing. The considerations of these adaptations are discussed. Successful strain-life testing data were acquired from a 4130 pressure vessel steel.

The synthetic molecule stauprimide impairs cell growth and migration in triple-negative breast cancer.

Stauprimide, a semi-synthetic derivative of staurosporine, is known mainly for its potent differentiation-enhancing properties in embryonic stem cells. Here, we studied the effects of stauprimide in cell growth and migration of triple-negative breast cancer cells in vitro, evaluating its potential antitumoral activity in an orthotopic mouse model of breast cancer in vivo. Our results from survival curves, EdU incorporation, cell cycle analysis and annexin-V detection in MDA-MB-231 cells indicated that stauprimide inhibited cell proliferation, arresting cell cycle in G2/M without induction of apoptosis. A decrease in the migratory capability of MDA-MB-231 was also assessed in response to stauprimide. In this work we pointed to a mechanism of action of stauprimide involving the modulation of ERK1/2, Akt and p38 MAPK signalling pathways, and the downregulation of MYC in MDA-MB-231 cells. In addition, orthotopic MDA-MB-231 xenograft and 4T1 syngeneic models suggested an effect of stauprimide in vivo, increasing the necrotic core of tumors and reducing metastasis in lung and liver of mice. Together, our results point to the promising role of stauprimide as a putative therapeutic agent in triple-negative breast cancer.

Content validity of the Benign Prostatic Hyperplasia Impact Index (BII); a measure of how urinary trouble and problems associated with BPH may impact the patient.

AIMS: The objective of this qualitative interview study was to assess the content validity of the Benign Prostatic Hyperplasia Impact Index (BII) in a sample of men with signs and symptoms of Benign Prostatic Obstruction believed to be caused by benign prostatic hyperplasia (BPH lower urinary tract symptoms/BPH-LUTS) using concept elicitation (CE) and cognitive interviewing (CI) methods. METHODS: Fifty men with BPH-LUTS participated in the study; 27 completed CE interviews and 23 completed cognitive interviews. RESULTS: Patient's average age was 69 years with a mean duration of BPH-LUTS of 6.5 years. IPSS scores ranged from 8 to 33 (higher scores indicating greater symptom severity). Overall, the most frequent symptoms (prevalence of ≥ 75%) reported spontaneously or after further explanation were awakening from sleep, increased daytime voiding (frequency), urgent desire to void (urgency), slow stream, and feeling of incomplete bladder emptying. Symptoms primarily recognized in response to follow up probe questions with a prevalence of ≥ 40% included terminal dribble, splitting of urinary stream, intermittent stream, straining and post-micturition dribble. Especially bothersome [> 5 on the numerical rating scale (NRS) of 0-10] and frequent symptoms included urgency and awakening at night to void. Discomfort or pain while urinating and post-micturition dribble were equally bothersome though less frequent. Five BPH symptom-related impact themes were identified: coping, daily responsibilities, emotion, lifestyle and relationships, and sleep. CONCLUSIONS: The BII was found to be easily understood, does capture clinically relevant BPH impacts related to urinary trouble and problems, and does capture most of the important symptom-related impacts as described by participants in this study.

The cyclooxygenase and nitric oxide synthesis/pathways mediate the inhibitory serotonergic response to the pressor effect elicited by sympathetic stimulation in long-term diabetic pithed rats.

We investigated the mechanisms involved in the 5-hydroxytriptaminergic inhibitory action on the pressor responses elicited by sympathostimulation in long-term-diabetic pithed rats. Diabetes was induced in rats by alloxan administration. Eight weeks later, the animals were anaesthetized and pithed. The action and mechanisms of 5-HT were analysed based on the pressor responses induced by sympathostimulation. In 8-week-diabetic animals, 5-HT (20 µg/kg/min) inhibits the pressor effect of sympathostimulation which is reproduced by two selective 5-HT(1A) and 5-HT(2) receptor agonists: 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT, 5 µg/kg/min) and α-methyl-5-HT (5 µg/kg/min). A bolus injection of 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ, 10 µg/kg), or L-arginine HCl, N(ω)-L-arginine methyl ester hydrochloride (L-NAME, 10 mg/kg), an inhibitor of NO production, prior to the infusion of 8-OH-DPAT (5 µg/kg/min) reversed the inhibitory effect of 8-OH-DPAT. The inhibitory effect of infusion of α-methyl 5-HT (5 µg/kg/min) was abolished in the presence of indomethacin (2 mg/kg), a non-selective cyclooxygenase (COX) inhibitor, or FR 122047 (1.5 mg/kg) or nimesulide (1.5 mg/kg), two selective COX-1 and COX-2 inhibitors, respectively, in long-term-diabetic pithed rats. Our results indicate that 5-HT inhibition of the pressor responses induced by electrical stimulation is mediated both by the NO and COX pathways in long-term-diabetic rats.

Quantitative (1) H MR spectroscopic imaging of the prostate gland using LCModel and a dedicated basis-set: correlation with histologic findings.

Proton magnetic resonance spectroscopic imaging ((1) H-MRSI) has been advocated as a valuable tool for prostate cancer diagnosis. However, a barrier to widespread clinical use of this technique is the lack of robust quantification methods that yield reproducible results in an institution-independent manner. The main goal of this study was to develop a standardized and fully automated approach (LCModel-based) for quantitative prostate (1) H-MRSI. To this end, a dedicated basis set was constructed by the combination of simulated (citrate, Cit; choline, Cho, and creatine, CR) and experimentally acquired (spermine, Spm) spectra. The overlapping Spm, Cho, and Cr could be resolved and quantified individually, thus allowing for the independent assessment of glandular (Cit and Spm) and proliferative (Cho) components. Several metabolite ratios were calculated and compared to the histologic findings of prostatectomy specimens from 10 prostate cancer patients with Gleason scores (3 + 3) and (3 + 4). The Cho mole fraction and the Cho/(Cit + Spm) ratio were found to best discriminate between prostate cancer and healthy tissue. The comparison between the quantitative MRSI results and the histologic findings suggests that no correlation exists between the detected metabolic alterations and the Gleason score of low-grade tumors.

Are the soft, liquid-like structures detected around bacteria by ambient dynamic atomic force microscopy capsules?

High-resolution imaging of bacterial capsules by microscopy is of paramount importance in microbiology due to their role in pathogenesis. This is, however, quite a challenging task due to their delicate nature. In this context, recent reports have claimed successful exploitation of the capacity of atomic force microscopy (AFM) for imaging of extremely deformable (even liquid) surfaces under ambient conditions to detect bacterial capsules in the form of tiny amounts of liquid-like substances around bacteria. In order to further explore this supposed capacity of AFM, in this work, three staphylococcal strains have been scrutinized for the presence of capsules using such an AFM-based approach with a phosphate buffer and water as the suspending liquids. Similar results were obtained with the three strains. AFM showed the presence of liquid-like substances identical to those attributed to bacterial capsules in the previous literature. Extensive imaging and chemical analysis point out the central role of the suspending liquid (buffer) in the formation of these substances. The phenomenon has been reproduced even by using nonliving particles, a finding that refutes the biological origin of the liquid-like substances visualized around the cells. Deliquescence of major components of biological buffers, such as K(2)HPO(4), CaCl(2), or HEPES, is proposed as the fundamental mechanism of the formation of these ultrasmall liquid-like structures. Such an origin could explain the high similarity of our results obtained with three very different strains and also the high similarity of these results to others reported in the literature based on other bacteria and suspending liquids. Finally, possible biological/biomedical implications of the presence of these ultrasmall amounts of liquids wrapping microorganisms are discussed.

Corrosion behaviour and biocompatibility of a novel Ni-free intermetallic coating growth on austenitic steel by hot dipping in an Al-12.6%Si alloy.

Commercial 316 LVM austenitic stainless steel samples have been coated by immersion in a bath of molten Al-12.6%Si alloy for 120 s. The coating consists of the Al(12)(Fe,Cr)(3)Si(2) intermetallic. In vitro corrosion behaviour has been evaluated in the Ringer's solution by means of potentiodynamic curves and electrochemical impedance spectroscopy. The results reveal that the coated specimens exhibit lower susceptibility to localised corrosion with respect to the substrate. XPS analysis suggests that the ennoblement of the pitting potential is due to the formation of a chromium oxyhydroxide containing passive layer. The intermetallic coating shows a good biocompatibility, as demonstrated by culturing human mesenchymal stem cells isolated from bone marrow which attached, grew and differentiated to the osteoblastic lineage to a similar extent on coated and bare steels. In summary, this study proposes a method that generates Ni-free coatings of the stainless steel with useful properties for biomedical applications.

Ionic liquid microdroplets as versatile lithographic molds for sculpting curved topographies on soft materials surfaces.

Soft lithography comprises a set of approaches for shaping the surface of soft materials such as PDMS on the microscopic scales. These procedures usually begin with the development of templates/masters normally generated by electron or photolithography techniques. However, the richness in available shapes is limited, usually producing shapes containing sharp parts. Innovation is called for to develop reliable approaches capable of imparting well-defined 3D curved shapes to these solids, a topology that is somehow unnatural for solid surfaces. Here we report on the use of tiny drops of room-temperature ionic liquid, organic liquids that have attracted increasing amounts of attention in recent years because of their unique chemical properties) as a versatile platform for imprinting PDMS with tunable 3D curved geometry, which is out of reach of conventional lithographic techniques and ranges from almost flat depressions to almost closed cavities on the millimeter to micrometer scale. The concept exploits a peculiar combination of physical properties displayed by ionic liquids as their null volatility and their polarity, together with some unique properties of liquid surfaces as their virtually null surface roughness. Proof-of-concept experiments show their application as chemical microreactors and ultrasmooth optical lenses. This all-liquid method is simple, low-cost, versatile, maskless, tension-free, and easily scalable, so we envision a community-wide application in numerous modern physical, chemical, biological, and engineering settings.

Strategic noise map of a major road carried out with two environmental prediction software packages.

The main objective of this study is to analyze the differences found in the results of noise mapping using two of the most popular software techniques for the prediction of environmental noise. The location selected to conduct the comparative study is an area encompassed by the ring road that surrounds the city of Pamplona and on a grid, with a total of 6 x 10(5) points, approximately. In fact, and as the Environmental Noise Directive points out, it is a major road designated by a Member State (Spain). Configuration of the calculation parameters (discretization of the sources, ground absorption, reflection order, etc.) was as equivalent as possible as far as programs allow. In spite of that, a great number of differences appear in the findings. Although in 95.5% of the points the difference in the noise level calculated from the two programs was less than 3 dB, this general statistic result concealed some great differences. These are due to the various algorithms that programs implement to evaluate noise levels. Most differences pertain to highly screened receivers or remote ones. In the former, the algorithm of visibility is the main cause of such differences. In the latter, differences are mainly brought about by a different implementation of the propagation under homogeneous and favorable atmospheric conditions from both software systems.

Structure, morphology, adhesion and in vitro biological evaluation of antibacterial multi-layer HA-Ag/SiO2/TiN/Ti coatings obtained by RF magnetron sputtering for biomedical applications.

Biocompatible and antibacterial multi-layer coatings of hydroxyapatite (HA)-Ag/SiO2/TiN/Ti were obtained on the Ti-6Al-4V alloy, by means of the magnetron sputtering technique. During characterization of the coatings, the chemical composition was evaluated by energy dispersive X-ray spectroscopy and the phase analysis was carried out by X-ray diffraction. The morphology of the coatings was observed by field emission scanning electron microscopy, while transmission electron microscopy was used to appreciate their structure. The adhesion of the coatings to the substrate was evaluated by micro scratch test. The in vitro biological response was evaluated in terms of cytotoxicity, adhesion and differentiation of mouse mesenchymal stem cells, as well as adhesion and bacterial viability of Staphylococcus aureus strain. Through the compositional study carried out, the deposition of the HA phase was verified, with a Ca/P ratio close to 1.67 and the characteristic diffraction peaks of this compound. The structural study of the coatings evidenced the obtention of multi-layer architectures. The use of an intermediate SiO2/TiN/Ti trilayer was found to improve adhesion between HA-Ag and the substrate by 84%. Finally, the in vitro biological tests carried out indicated a potentially non-toxic character in the coatings. Additionally, an antibacterial effect was registered at low concentrations of Ag (<0.25 mg/L).

[Development of a risk map in an oral and maxillofacial surgical unit]. / Desarrollo de un mapa de riesgos en una unidad de cirugía oral y maxilofacial.

INTRODUCTION: the main aim of this study was to develop and implement a risk map in the Oral and Maxillofacial Surgery Service of the University Hospital «Virgen de las Nieves¼ of Granada to minimize the incidence of adverse effects (AE). MATERIALS AND METHODS: Longitudinal, prospective study carried out in the Oral and Maxillofacial Surgery Service of the Hospital Universitario Virgen de las Nieves of Granada, from June 2017 to May 2018, through the methodology of «Analysis and Failure Mode Effect¼. Management of the different AE was addressed. The following phases were considered as it follows: identification of the problem, identification of AE for within the practice of the oral and maxillofacial surgery that represents a problem in the assistive safety, creation of an interdisciplinary working group, analysis of the current situation in patient safety and risk management using 2analysis tools, SWOT and PITELO, preparation of the patient care process, development of a catalog of AE and preparation of a risk map. RESULTS: A total of 33 AE were identified. The risk map showed a higher incidence of AE in the Surgical Area (22) compared to the areas of Outpatient Clinic and Hospital Discharge (6). A total of 10 critical AE were identified. CONCLUSIONS: The elaboration of a risk map allowed to determine the process of the oral and maxillofacial surgical patient, and to elaborate a catalog of AE.

The role of the nurse at the end of the life of a critically ill patient. / Rol de la enfermera en el cuidado al final de la vida del paciente crítico.

OBJECTIVE: Analyze the role of the nurse at the end of the life of a critically ill patient. METHOD: Bibliographic review from a search of the health science databases such as PubMed, CINAHL, Cuiden, Scopus, Cochrane, as well as specialized platforms, general and thematic browsers. The limits were language (English or Spanish) and publication date (2005-2015). RESULTS: 180 articles met the inclusion criteria, and 16 of them were selected for analysis. The main results were grouped into three categories of analysis: direct patient care, family-focussed care and the nurse's role within the team. CONCLUSIONS: the described roles place the nurse as a key element in humanising death in the ICU and so nurses can and must lead change, playing an active role in creating strategies that really promote the integration of a palliative care approach in ICU.