Abstract
The coronavirus disease 2019 (COVID-19) is the latest biological hazard for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though numerous diagnostic tests for ...SARS-CoV-2 have been proposed, new diagnosis strategies are being developed, looking for less expensive methods to be used as screening. This study aimed to establish salivary vibrational modes analyzed by attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy to detect COVID-19 biological fingerprints that allow the discrimination between COVID-19 and healthy patients. Clinical dates, laboratories, and saliva samples of COVID-19 patients (N = 255) and healthy persons (N = 1209) were obtained and analyzed through ATR-FTIR spectroscopy. Then, a multivariate linear regression model (MLRM) was developed. The COVID-19 patients showed low SaO
2
, cough, dyspnea, headache, and fever principally. C-reactive protein, lactate dehydrogenase, fibrinogen,
d
-dimer, and ferritin were the most important altered laboratory blood tests, which were increased. In addition, changes in amide I and immunoglobulin regions were evidenced in the FTIR spectra analysis, and the MLRM showed clear discrimination between both groups. Specific salivary vibrational modes employing ATR-FTIR spectroscopy were established; moreover, the COVID-19 biological fingerprint in saliva was characterized, allowing the COVID-19 detection using an MLRM, which could be helpful for the development of new diagnostic devices.
Idiopathic pulmonary fibrosis (IPF) is a devastating disease that probably involves several genetic loci. Several rare genetic variants and one common single nucleotide polymorphism (SNP) of MUC5B ...have been associated with the disease. Our aim was to identify additional common variants associated with susceptibility and ultimately mortality in IPF.
First, we did a three-stage genome-wide association study (GWAS): stage one was a discovery GWAS; and stages two and three were independent case-control studies. DNA samples from European-American patients with IPF meeting standard criteria were obtained from several US centres for each stage. Data for European-American control individuals for stage one were gathered from the database of genotypes and phenotypes; additional control individuals were recruited at the University of Pittsburgh to increase the number. For controls in stages two and three, we gathered data for additional sex-matched European-American control individuals who had been recruited in another study. DNA samples from patients and from control individuals were genotyped to identify SNPs associated with IPF. SNPs identified in stage one were carried forward to stage two, and those that achieved genome-wide significance (p<5 × 10(-8)) in a meta-analysis were carried forward to stage three. Three case series with follow-up data were selected from stages one and two of the GWAS using samples with follow-up data. Mortality analyses were done in these case series to assess the SNPs associated with IPF that had achieved genome-wide significance in the meta-analysis of stages one and two. Finally, we obtained gene-expression profiling data for lungs of patients with IPF from the Lung Genomics Research Consortium and analysed correlation with SNP genotypes.
In stage one of the GWAS (542 patients with IPF, 542 control individuals matched one-by-one to cases by genetic ancestry estimates), we identified 20 loci. Six SNPs reached genome-wide significance in stage two (544 patients, 687 control individuals): three TOLLIP SNPs (rs111521887, rs5743894, rs5743890) and one MUC5B SNP (rs35705950) at 11p15.5; one MDGA2 SNP (rs7144383) at 14q21.3; and one SPPL2C SNP (rs17690703) at 17q21.31. Stage three (324 patients, 702 control individuals) confirmed the associations for all these SNPs, except for rs7144383. Linkage disequilibrium between the MUC5B SNP (rs35705950) and TOLLIP SNPs (rs111521887 r(2)=0·07, rs5743894 r(2)=0·16, and rs5743890 r(2)=0·01) was low. 683 patients from the GWAS were included in the mortality analysis. Individuals who developed IPF despite having the protective TOLLIP minor allele of rs5743890 carried an increased mortality risk (meta-analysis with fixed-effect model: hazard ratio 1·72 95% CI 1·24-2·38; p=0·0012). TOLLIP expression was decreased by 20% in individuals carrying the minor allele of rs5743890 (p=0·097), 40% in those with the minor allele of rs111521887 (p=3·0 × 10(-4)), and 50% in those with the minor allele of rs5743894 (p=2·93 × 10(-5)) compared with homozygous carriers of common alleles for these SNPs.
Novel variants in TOLLIP and SPPL2C are associated with IPF susceptibility. One novel variant of TOLLIP, rs5743890, is also associated with mortality. These associations and the reduced expression of TOLLIP in patients with IPF who carry TOLLIP SNPs emphasise the importance of this gene in the disease.
National Institutes of Health; National Heart, Lung, and Blood Institute; Pulmonary Fibrosis Foundation; Coalition for Pulmonary Fibrosis; and Instituto de Salud Carlos III.
Differences in the lung microbial community influence idiopathic pulmonary fibrosis (IPF) progression. Whether the lung microbiome influences IPF host defense remains unknown.
To explore the host ...immune response and microbial interaction in IPF as they relate to progression-free survival (PFS), fibroblast function, and leukocyte phenotypes.
Paired microarray gene expression data derived from peripheral blood mononuclear cells as well as 16S ribosomal RNA sequencing data from bronchoalveolar lavage obtained as part of the COMET-IPF (Correlating Outcomes with Biochemical Markers to Estimate Time-Progression in Idiopathic Pulmonary Fibrosis) study were used to conduct association pathway analyses. The responsiveness of paired lung fibroblasts to Toll-like receptor 9 (TLR9) stimulation by CpG-oligodeoxynucleotide (CpG-ODN) was integrated into microbiome-gene expression association analyses for a subset of individuals. The relationship between associated pathways and circulating leukocyte phenotypes was explored by flow cytometry.
Down-regulation of immune response pathways, including nucleotide-binding oligomerization domain (NOD)-, Toll-, and RIG1-like receptor pathways, was associated with worse PFS. Ten of the 11 PFS-associated pathways correlated with microbial diversity and individual genus, with species accumulation curve richness as a hub. Higher species accumulation curve richness was significantly associated with inhibition of NODs and TLRs, whereas increased abundance of Streptococcus correlated with increased NOD-like receptor signaling. In a network analysis, expression of up-regulated signaling pathways was strongly associated with decreased abundance of operational taxonomic unit 1341 (OTU1341; Prevotella) among individuals with fibroblasts responsive to CpG-ODN stimulation. The expression of TLR signaling pathways was also linked to CpG-ODN responsive fibroblasts, OTU1341 (Prevotella), and Shannon index of microbial diversity in a network analysis. Lymphocytes expressing C-X-C chemokine receptor 3 CD8 significantly correlated with OTU1348 (Staphylococcus).
These findings suggest that host-microbiome interactions influence PFS and fibroblast responsiveness.
To compare the usefulness of four prognostic scores in patients with peripheral T-cell lymphoma (PTCL) from a single institution.
One hundred twenty-one patients (77 male/36 female, median age 53 ...years) with PTCL anaplastic large-cell lymphoma (ALCL) 21, PTCL not otherwise specified 56 and other 44). Complete response (CR) rate and 5-year overall survival (OS) were 41% and 31%, respectively. International Prognostic Index (IPI), Prognostic Index for T-cell lymphoma (PIT), International peripheral T-cell lymphoma Project score (IPTCLP) and modified Prognostic Index for T-cell lymphoma (mPIT) were calculated as in the original references. mPIT was only assembled to 41 patients in whom Ki-67 immunostaining was available. ALCL patients were analyzed separately.
Concordance among IPI, PIT and IPTCLP was 52% for low-risk group, 27% for low/intermediate-risk group, 20% for high/intermediate-risk group and 14% for high-risk group. IPI, PIT and IPTCLP predicted CR, with IPI being the best score in logistic regression. Neither Ki-67 immunostaining nor mPIT predicted CR. Five-year OS (low-risk versus intermediate- or high-risk categories) according to IPI, PIT, IPTCLP and mPIT were 52% versus 45%, 75% versus 49%, 58% versus 20% and 39% versus 0%, respectively. IPTCLP was the best score for OS in multivariate analysis.
All the scores demonstrated their usefulness to assess the outcome of patients with PTCL, with IPTCLP being the most significant to predict OS.
To assess risk factors for multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection in neutropenic patients.
Single-centre retrospective analysis of consecutive bloodstream infection (BSI) ...episodes (2004–2017, Barcelona). Two multivariate regression models were used at BSI diagnosis and P. aeruginosa detection. Significant predictors were used to establish rules for stratifying patients according to MDR-PA BSI risk.
Of 661 Gram-negative BSI episodes, 190 (28.7%) were caused by P. aeruginosa (70 MDR-PA). Independent factors associated with MDR-PA among Gram-negative organisms were haematological malignancy (OR 3.30; 95% CI 1.15–9.50), pulmonary source of infection (OR 7.85; 95% CI 3.32–18.56), nosocomial-acquired BSI (OR 3.52; 95% CI 1.74–7.09), previous antipseudomonal cephalosporin (OR 13.66; 95% CI 6.64–28.10) and piperacillin/tazobactam (OR 2.42; 95% CI 1.04–5.63), and BSI occurring during ceftriaxone (OR 4.27; 95% CI 1.15–15.83). Once P. aeruginosa was identified as the BSI aetiological pathogen, nosocomial acquisition (OR 7.13; 95% CI 2.87–17.67), haematological malignancy (OR 3.44; 95% CI 1.07–10.98), previous antipseudomonal cephalosporin (OR 3.82; 95% CI 1.42–10.22) and quinolones (OR 3.97; 95% CI 1.37–11.48), corticosteroids (OR 2.92; 95% CI 1.15–7.40), and BSI occurring during quinolone (OR 4.88; 95% CI 1.58–15.05) and β-lactam other than ertapenem (OR 4.51; 95% CI 1.45–14.04) were independently associated with MDR-PA. Per regression coefficients, 1 point was assigned to each parameter, except for nosocomial-acquired BSI (3 points). In the second analysis, a score >3 points identified 60 (86.3%) out of 70 individuals with MDR-PA BSI and discarded 100 (84.2%) out of 120 with non-MDR-PA BSI.
A simple score based on demographic and clinical factors allows stratification of individuals with bacteraemia according to their risk of MDR-PA BSI, and may help facilitate the use of rapid MDR-detection tools and improve early antibiotic appropriateness.
Four strategies of deficit irrigation based on a different water-stress ratio (WSR) applied in each phenological stage, and a control treatment were implemented in 11-year-old citrus trees (
Citrus ...sinensis L. Osb. Cv.
Navelina) grafted onto carrizo citrange (
C. sinensis L. Osb.
×
Poncirus Trifoliata L. Osb.). The midday stem-water potential and stomatal conductance were measured during the periods considered, and these parameters were used to estimate the plant-water status. Integrated stem-water potential (
Ψ
Int) and integrated stomatal conductance (
g
Int) were calculated for all treatments and used as a water-stress indicator for the crop. Reference equations were formulated to quantify the relations between water-stress indicators (WSR,
Ψ
Int,
g
Int) and the crop response, expressed as yield, yield components, and fruit-quality parameters under limited seasonal water availability. Significant differences in yield were found in the second year of experiment between the stressed treatments and control, although these differences were evident during the first year. The main effects were detected in treatments with a water-sever stress applied during the flowering and fruit-growth phases. When this degree of stress was applied during the maturity phase, it was reflected mainly in fruit-quality parameters (total soluble solids, and titrable acidity). These results lead to the conclusion that, in mature orange trees, deficit irrigation affects yield and fruit quality, while enabling water savings of up to 1000
m
3
ha
−1. Therefore, yield declined on average 10–12% but boosted water productivity 24% with respect to the fully irrigated treatment. Regarding the water-stress indicators used,
Ψ
Int and
g
Int showed highly significant correlations with the yield and fruit-quality parameters.
•CdS thin films by conventional CBD and laser assisted CBD.•Characterized these films using XRD, XPS, AFM, optical and electrical measurements.•Accelerated growth was observed in the laser assisted ...CBD process.•Improved dark conductivity and good photocurrent response for the LACBD CdS.
In this work, we report the preparation and characterization of CdS thin films by laser assisted chemical bath deposition (LACBD). CdS thin films were prepared from a chemical bath containing cadmium chloride, triethanolamine, ammonium hydroxide and thiourea under various deposition conditions. The thin films were deposited by in situ irradiation of the bath using a continuous laser of wavelength 532nm, varying the power density. The thin films obtained during deposition of 10, 20 and 30min were analyzed. The changes in morphology, structure, composition, optical and electrical properties of the CdS thin films due to in situ irradiation of the bath were analyzed by atomic force microscopy (AFM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and UV–vis spectroscopy. The thin films obtained by LACBD were nanocrystalline, photoconductive and presented interesting morphologies. The results showed that LACBD is an effective synthesis technique to obtain nanocrystalline CdS thin films having good optoelectronic properties.
The COVID-19 pandemic presents a significant infection prevention and control challenge. The admission of large numbers of patients with suspected COVID-19 disease risks overwhelming the capacity to ...protect other patients from exposure. The delay between clinical suspicion and confirmatory testing adds to the complexity of the problem.
We implemented a triage tool aimed at minimizing hospital-acquired COVID-19 particularly in patients at risk of severe disease. Patients were allocated to triage categories defined by likelihood of COVID-19 and risk of a poor outcome. Category A (low-likelihood; high-risk), B (high-likelihood; high-risk), C (high-likelihood; low-risk) and D (low-likelihood; low-risk). This determined the order of priority for isolation in single-occupancy rooms with Category A the highest. Patients in other groups were cohorted when isolation capacity was limited with additional interventions to reduce transmission.
Ninety-three patients were evaluated with 79 (85%) receiving a COVID-19 diagnosis during their admission. Of those without a COVID-19 diagnosis: 10 were initially triaged to Category A; 0 to B; 1 to C and 4 to D. All high-risk patients requiring isolation were, therefore, admitted to single-occupancy rooms and protected from exposure. Twenty-eight (30%) suspected COVID-19 patients were evaluated to be low risk (groups C and D) and eligible for cohorting. No symptomatic hospital-acquired infections were detected in the cohorted patients.
Application of a clinical triage tool to guide isolation and cohorting decisions may reduce the risk of hospital-acquired transmission of COVID-19 especially to individuals at the greatest of risk of severe disease.
We present a detailed description of the electromagnetic filter for the PTOLEMY project to directly detect the Cosmic Neutrino Background (CNB). Starting with an initial estimate for the orbital ...magnetic moment, the higher-order drift process of E×B is configured to balance the gradient-B drift motion of the electron in such a way as to guide the trajectory into the standing voltage potential along the mid-plane of the filter. As a function of drift distance along the length of the filter, the filter zooms in with exponentially increasing precision on the transverse velocity component of the electron kinetic energy. This yields a linear dimension for the total filter length that is exceptionally compact compared to previous techniques for electromagnetic filtering. The parallel velocity component of the electron kinetic energy oscillates in an electrostatic harmonic trap as the electron drifts along the length of the filter. An analysis of the phase-space volume conservation validates the expected behavior of the filter from the adiabatic invariance of the orbital magnetic moment and energy conservation following Liouville’s theorem for Hamiltonian systems.
Chronic kidney disease (CKD) affects the kidneys, and in severe cases is considered as end-stage renal disease which can only be treated by dialysis and transplantation. Tierra Blanca city has a ...higher CKD rate compared to other Mexican cities, but its principal cause has not been found yet. Main factors related to CKD are carbonated beverage consumption, diabetes, obesity, hypertension, heat stress, dehydration, and intoxication by pesticides, heavy metals, and/or hydrocarbons. The aim of this work was to evaluate hydrocarbon pollution in Tierra Blanca domestic fresh-water related to CKD and to integrate this information with other main factors in order to suggest precautionary actions taking account of key actors. We found hydrocarbons in the water wells of the city and the presence of other risk factors, which creates a perfect storm for CKD. Additionally, key actors were identified in order to follow precautionary principles related to CKD cases in Tierra Blanca.
•Tierra Blanca city has a higher CKD rate compared to other Mexican cities.•We found hydrocarbons in the water wells of Tierra Blanca.•The presence of other risk factors creates a perfect storm for CKD.•Key actors were identified in order to follow precautionary principle related to CKD.
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