COVID-19 in lung transplant recipients: A multicenter study.

This study describes the clinical presentation, treatment, and outcomes of SARS-CoV-2 infection in lung transplant recipients (LTRs). This is a multicenter, retrospective study of all adult LTRs with confirmed SARS-CoV-2 infection from March 4 until April 28, 2020 in six Spanish reference hospitals for lung transplantation. Clinical and radiological data, treatment characteristics, and outcomes were reviewed. Forty-four cases were identified in that period. The median time from transplantation was 4.2 (interquartile range: 1.11-7.3) years. Chest radiography showed acute parenchymal abnormalities in 32 (73%) cases. Hydroxychloroquine was prescribed in 41 (93%), lopinavir/ritonavir (LPV/r) in 14 (32%), and tocilizumab in 19 (43%) patients. There was a strong interaction between tacrolimus and LPV/r in all cases. Thirty-seven (84%) patients required some degree of respiratory support and/or oxygen therapy, and 13 (30%) were admitted to intermediate or intensive critical care units. Seventeen (39%) patients had died and 20 (45%) had been discharged at the time of the last follow-up. Deceased patients had a worse respiratory status and chest X-ray on admission and presented with higher D-dimer, interleukin-6, and lactate dehydrogenase levels. In this multicenter LTR cohort, SARS-CoV-2 presented with high mortality. Additionally, the severity of disease on presentation predicted subsequent mortality.

Characterization of tick salivary gland and saliva alphagalactome reveals candidate alpha-gal syndrome disease biomarkers.

BACKGROUND: Ticks are obligate hematophagous arthropods that synthesize the glycan Galα1-3Galß1-(3)4GlcNAc-R (α-Gal) associated with the alpha-gal syndrome (AGS) or allergy to mammalian meat consumption. RESEARCH DESIGN AND METHODS: In this study, we used a proteomics approach to characterize tick proteins in salivary glands (sialome SG), secreted saliva (sialome SA) and with α-Gal modification (alphagalactome SG and SA) in model tick species associated with the AGS in the United States (Amblyomma americanum) and Australia (Ixodes holocyclus). Selected proteins reactive to sera (IgE) from patients with AGS were identified to advance in the identification of possible proteins associated with the AGS. For comparative analysis, the α-Gal content was measured in various tick species. RESULTS: The results confirmed that ticks produce proteins with α-Gal modifications and secreted into saliva during feeding. Proteins identified in tick alphagalactome SA by sera from patients with severe AGS symptomatology may constitute candidate disease biomarkers. CONCLUSIONS: The results support the presence of tick-derived proteins with α-Gal modifications in the saliva with potential implications in AGS and other disorders and protective capacity against tick infestations and pathogen infection. Future research should focus on the characterization of the function of tick glycoproteins with α-Gal in tick biology and AGS.

Ticks from diverse genera encode chemokine-inhibitory evasin proteins.

To prolong residence on their hosts, ticks secrete many salivary factors that target host defense molecules. In particular, the tick Rhipicephalus sanguineus has been shown to produce three salivary glycoproteins named "evasins," which bind to host chemokines, thereby inhibiting the recruitment of leukocytes to the location of the tick bite. Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family. Nine representative sequences were successfully expressed in Escherichia coli, and eight of the nine candidates exhibited high-affinity binding to human chemokines. Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds. Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation. We conclude that chemokine-binding evasin proteins are widely expressed among tick species of the Ixodidae family, are likely to play important roles in subverting host defenses, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.

Discovery of a novel iflavirus sequence in the eastern paralysis tick Ixodes holocyclus.

Ixodes holocyclus, the eastern paralysis tick, is a significant parasite in Australia in terms of animal and human health. However, very little is known about its virome. In this study, next-generation sequencing of I. holocyclus salivary glands yielded a full-length genome sequence which phylogenetically groups with viruses classified in the Iflaviridae family and shares 45% amino acid similarity with its closest relative Bole hyalomma asiaticum virus 1. The sequence of this virus, provisionally named Ixodes holocyclus iflavirus (IhIV) has been identified in tick populations from northern New South Wales and Queensland, Australia and represents the first virus sequence reported from I. holocyclus.

Risk Factors of Poor Outcomes after Admission for a COPD Exacerbation: Multivariate Logistic Predictive Models.

The aim of this study was to identify a multivariate model to predict poor outcomes after admission for exacerbation of chronic obstructive pulmonary disease (COPD).  We performed a multicenter, observational, prospective study. Patients admitted to hospital for COPD were followed up for 3 months. Relevant clinical variables at admission were selected. For each variable, the best cut-offs for the risk of poor outcome were identified using receiver operating characteristic (ROC) curves. Finally, a stepwise logistic regression model was performed. A total of 106 patients with a mean age of 71.1 (9.8) years were included. The mean maximum expiratory volume in the first second (FEV1)(%) was 45.2%, and the mean COPD assessment test (CAT) score at admission was 24.8 (7.1). At 3 months, 39 (36.8%) patients demonstrated poor outcomes: death (2.8%), readmission (20.8%) or new exacerbation (13.2%). Variables included in the logistic model were: previous hospital admission, FEV1 < 45%, Charlson ≥ 3, hemoglobin (Hb)<13 g/L, PCO2 ≥ 46 mmHg, fibrinogen ≥ 554 g/L, C-reactive protein (CRP)≥45 mg/L, leukocyte count < 9810 × 109/L, purulent sputum, long-term oxygen therapy (LTOT) and CAT ≥ 31 at admission. The final model showed that Hb < 13 g/L (OR = 2.46, 95%CI 1.09-6.36), CRP ≥ 45 mg/L (OR = 2.91, 95%CI: 1.11-7.49) and LTOT (3.07, 95%CI: 1.07-8.82) increased the probability of poor outcome up to 82.4%. Adding a CAT ≥ 31 at admission increased the probability to 91.6% (AUC = 0.75; p = 0.001). Up to 36.8% of COPD patients had a poor outcome within 3 months after hospital discharge, with low hemoglobin and high CRP levels being the risk factors for poor outcome. A high CAT at admission increased the predictive value of the model.

Impact of Microalgae-Bacteria Interactions on the Production of Algal Biomass and Associated Compounds.

A greater insight on the control of the interactions between microalgae and other microorganisms, particularly bacteria, should be useful for enhancing the efficiency of microalgal biomass production and associated valuable compounds. Little attention has been paid to the controlled utilization of microalgae-bacteria consortia. However, the studies of microalgal-bacterial interactions have revealed a significant impact of the mutualistic or parasitic relationships on algal growth. The algal growth, for instance, has been shown to be enhanced by growth promoting factors produced by bacteria, such as indole-3-acetic acid. Vitamin B12 produced by bacteria in algal cultures and bacterial siderophores are also known to be involved in promoting faster microalgal growth. More interestingly, enhancement in the intracellular levels of carbohydrates, lipids and pigments of microalgae coupled with algal growth stimulation has also been reported. In this sense, massive algal production might occur in the presence of bacteria, and microalgae-bacteria interactions can be beneficial to the massive production of microalgae and algal products. This manuscript reviews the recent knowledge on the impact of the microalgae-bacteria interactions on the production of microalgae and accumulation of valuable compounds, with an emphasis on algal species having application in aquaculture.

Immunomic Investigation of Holocyclotoxins to Produce the First Protective Anti-Venom Vaccine Against the Australian Paralysis Tick, Ixodes holocyclus.

Venom producing animals are ubiquitously disseminated among vertebrates and invertebrates such as fish, snakes, scorpions, spiders, and ticks. Of the ~890 tick species worldwide, 27 have been confirmed to cause paralysis in mammalian hosts. The Australian paralysis tick (Ixodes holocyclus) is the most potent paralyzing tick species known. It is an indigenous three host tick species that secretes potent neurotoxins known as holocyclotoxins (HTs). Holocyclotoxins cause a severe and harmful toxicosis leading to a rapid flaccid paralysis which can result in death of susceptible hosts such as dogs. Antivenins are generally polyclonal antibody treatments developed in sheep, horses or camels to administer following bites from venomous creatures. Currently, the methods to prevent or treat tick paralysis relies upon chemical acaricide preventative treatments or prompt removal of all ticks attached to the host followed by the administration of a commercial tick-antiserum (TAS) respectively. However, these methods have several drawbacks such as poor efficacies, non-standardized dosages, adverse effects and are expensive to administer. Recently the I. holocyclus tick transcriptome from salivary glands and viscera reported a large family of 19 holocyclotoxins at 38-99% peptide sequence identities. A pilot trial demonstrated that correct folding of holocyclotoxins is needed to induce protection from paralysis. The immunogenicity of the holocyclotoxins were measured using commercial tick antiserum selecting HT2, HT4, HT8 and HT11 for inclusion into the novel cocktail vaccine. A further 4 HTs (HT1, HT12, HT14 and HT17) were added to the cocktail vaccine to ensure that the sequence variation among the HT protein family was encompassed in the formulation. A second trial comparing the cocktail of 8 HTs to a placebo group demonstrated complete protection from tick challenge. Here we report the first successful anti-venom vaccine protecting dogs from tick paralysis.

Comparative microarray analysis of Rhipicephalus (Boophilus) microplus expression profiles of larvae pre-attachment and feeding adult female stages on Bos indicus and Bos taurus cattle.

BACKGROUND: Rhipicephalus (Boophilus) microplus is an obligate blood feeder which is host specific to cattle. Existing knowledge pertaining to the host or host breed effects on tick transcript expression profiles during the tick - host interaction is poor. RESULTS: Global analysis of gene expression changes in whole R. microplus ticks during larval, pre-attachment and early adult stages feeding on Bos indicus and Bos taurus cattle were compared using gene expression microarray analysis. Among the 13,601 R. microplus transcripts from BmiGI Version 2 we identified 297 high and 17 low expressed transcripts that were significantly differentially expressed between R. microplus feeding on tick resistant cattle [Bos indicus (Brahman)] compared to R. microplus feeding on tick susceptible cattle [Bos taurus (Holstein-Friesian)] (p

Evidence of a tick RNAi pathway by comparative genomics and reverse genetics screen of targets with known loss-of-function phenotypes in Drosophila.

BACKGROUND: The Arthropods are a diverse group of organisms including Chelicerata (ticks, mites, spiders), Crustacea (crabs, shrimps), and Insecta (flies, mosquitoes, beetles, silkworm). The cattle tick, Rhipicephalus (Boophilus) microplus, is an economically significant ectoparasite of cattle affecting cattle industries world wide. With the availability of sequence reads from the first Chelicerate genome project (the Ixodes scapularis tick) and extensive R. microplus ESTs, we investigated evidence for putative RNAi proteins and studied RNA interference in tick cell cultures and adult female ticks targeting Drosophila homologues with known cell viability phenotype. RESULTS: We screened 13,643 R. microplus ESTs and I. scapularis genome reads to identify RNAi related proteins in ticks. Our analysis identified 31 RNAi proteins including a putative tick Dicer, RISC associated (Ago-2 and FMRp), RNA dependent RNA polymerase (EGO-1) and 23 homologues implicated in dsRNA uptake and processing. We selected 10 R. microplus ESTs with >80% similarity to D. melanogaster proteins associated with cell viability for RNAi functional screens in both BME26 R. microplus embryonic cells and female ticks in vivo. Only genes associated with proteasomes had an effect on cell viability in vitro. In vivo RNAi showed that 9 genes had significant effects either causing lethality or impairing egg laying. CONCLUSION: We have identified key RNAi-related proteins in ticks and along with our loss-of-function studies support a functional RNAi pathway in R. microplus. Our preliminary studies indicate that tick RNAi pathways may differ from that of other Arthropods such as insects.

Non-small cell lung cancer and silent brain metastasis. Survival and prognostic factors.

The detection of silent brain metastasis is becoming increasingly common in patients with non-small cell lung cancer (NSCLC). The aim of this study was to evaluate clinical course, prognostic significance, and treatment efficacy in patients with asymptomatic brain metastasis. A retrospective study of patients with cytologically and histologically diagnosed NSCLC and brain metastasis detected by cranial computed tomography or magnetic resonance imaging was performed. We compared 12 neurologically asymptomatic patients to 69 symptomatic patients and analyzed overall survival, clinical course, and prognostic factors (age, sex, performance status, histologic type, TNM stage, number and size of brain metastases, clinical neurologic status, and treatment of primary tumor and brain metastasis). The strongest favorable prognostic factor was active treatment of both the primary tumor (surgery, chemotherapy and/or thoracic radiotherapy) and brain metastasis (neurosurgery and/or whole brain radiotherapy). Neurologically asymptomatic patients had significantly longer survival times than did symptomatic patients (median survival of 7.5 and 4 months, respectively). Control of clinical neurologic status during follow-up was achieved in a greater proportion of asymptomatic patients (80%) than symptomatic patients (40%). We conclude that it is important to detect brain metastasis in patients with NSCLC before neurologic signs or symptoms develop, as early detection improves prognosis and provides patients with the opportunity of receiving timely and more effective treatment.

Impedimetric detection of double-tagged PCR products using novel amplification procedures based on gold nanoparticles and Protein G.

Double-tagged DNA coming from PCR amplification of a Salmonella spp. sample was detected by an electrochemical impedimetric genosensor based on avidin bulk-modified graphite-epoxy biocomposite (Av-GEB). The double-tagging PCR strategy provided the amplicon with both biotin and digoxigenin (DIG) moieties. The immobilization of the double-tagged DNA was based on its biotin moiety, while the DIG label was used for signal amplification. Impedance spectra were recorded to detect the change in interfacial charge transfer resistance (R(ct)), experimented by the redox marker ferri-/ferro-cyanide after the avidin-biotin fixation of the sample DNA onto the electrode surface. A further step in the genosensing strategy was the amplification of impedimetric signal by the use of an enhancing procedure. The latter was based on the reaction of the DIG moiety belonging to the amplicon with an anti-DIG antibody from mouse. Two different secondary enhancing steps based both on gold nanoparticle-labelled anti-mouse IgG or on Protein G were performed and compared for improving assay sensitivity.

Instability of the Rayleigh-Jeans spectrum in weak wave turbulence theory.

We study the four-wave kinetic equation of weak turbulence linearized around the Rayleigh-Jeans spectrum when the collision integral is associated with short-range interactions between nonrelativistic bosonic quasiparticles. The technique used for the analysis of the stability is based on the properties of the Mellin transform of the kernel in the integral equation. We find that any perturbation of the Rayleigh-Jeans distribution evolves toward low-momentum scales in such a form that when t-->infinity, all the particles occupy a sphere of radius arbitrary small.

Antibacterial and antifungal activity of defensins from the Australian paralysis tick, Ixodes holocyclus.

Tick innate immunity involves humoral and cellular responses. Among the humoral effector molecules in ticks are the defensins which are a family of small peptides with a conserved γ-core motif that is crucial for their antimicrobial activity. Defensin families have been identified in several hard and soft tick species. However, little is known about the presence and antimicrobial activity of defensins from the Australian paralysis tick Ixodes holocyclus. In this study the I. holocyclus transcriptome was searched for the presence of defensins. Unique and non-redundant defensin sequences were identified and designated as holosins 1 - 5. The antimicrobial activity of holosins 2 and 3 and of the predicted γ-cores of holosins 1-4 (HoloTickCores 1-4), was assessed using Gram-negative and Gram-positive bacteria as well as the fungus Fusarium graminearum and the yeast Candida albicans. All holosins had molecular features that are conserved in other tick defensins. Furthermore holosins 2 and 3 were very active against the Gram-positive bacteria Staphylococcus aureus and Listeria grayi. Holosins 2 and 3 were also active against F. graminearum and C. albicans and 5 µM of peptide abrogate the growth of these microorganisms. The activity of the synthetic γ-cores was lower than that of the mature defensins apart from HoloTickCore 2 which had activity comparable to mature holosin 2 against the Gram-negative bacterium Escherichia coli. This study reveals the presence of a multigene defensin family in I. holocyclus with wide antimicrobial activity.

Low genetic diversity of Ehrlichia canis associated with high co-infection rates in Rhipicephalus sanguineus (s.l.).

BACKGROUND: Rhipicephalus sanguineus sensu lato (s.l.) is the most widely distributed ixodid tick and is a vector of major canine and human pathogens. High-throughput technologies have revealed that individual ticks carry a high diversity of pathogens, including bacteria, protozoa and viruses. Currently, it is accepted that co-infections (multiple pathogen species within an individual) are very common in ticks and influence pathogen acquisition and transmission as well as host infection risk. However, little is known on the impact of the genetic diversity of pathogens on the incidence of co-infections. Herein, we studied the frequency of co-infections in R. sanguineus (s.l.) and their association with the genetic diversity of Ehrlichia canis. METHODS: Rhipicephalus sanguineus (s.l.) female ticks (n = 235) were collected from healthy farm dogs in three districts of Pakistan. Microfluidic real-time PCR, a powerful nanotechnology for high-throughput molecular detection of pathogens, was used to test the presence of 25 bacterial and seven parasitic species in individual ticks. The genetic diversity of E. canis was evaluated by characterizing the trp36 gene. RESULTS: A total of 204 ticks were infected with at least one pathogen and 109 co-infected with two (80%) or three (20%) pathogens. Rickettsia massiliae (human pathogen) and E. canis (zoonotic dog pathogen) were the most common pathogens co-infecting (30.4%) ticks. Furthermore, all identified co-infections included R. massiliae and/or E. canis. Multiple correspondence analysis (MCA) revealed that single infections did not show clear regional association whereas some co-infections were restricted to certain geographical regions. The sequence analysis of trp36 in representative samples allowed the identification of three E. canis strains with low genetic diversity, and the strain found in Muzaffargarh district appeared to be more adapted to co-infection with R. massiliae. CONCLUSIONS: Rhipicephalus sanguineus (s.l.) harbors multiple co-infections with human and dog pathogens of zoonotic potential. Findings of this study suggest that genetic diversity of E. canis may favor co-infections with different pathogens.

Nutrient solution monitoring in greenhouse cultivation employing a potentiometric electronic tongue.

This work investigates the use of electronic tongues for monitoring nutrient solution compositions in closed soilless systems. This is a horticultural technique in which the nutrient solution is continuously recirculated and an automatic recomposition system maintains the concentration of the different ions in the optimum range for the plants. Electronic tongues used in this study comprised an array of potentiometric sensors and complex data processing by artificial neural networks. A first experiment was able to carry out the simultaneous inline monitoring of ammonium, potassium, sodium, chloride, and nitrate ions during the winter. In the second and third applications, done during summer, some changes were introduced in the sensor array to improve its response toward chloride ions and to incorporate phosphate in the model. This electronic tongue was validated with real greenhouse samples and was also able to detect the variations in the ion concentrations caused by an incorrect configuration of the recomposition system.

Automated electronic tongue based on potentiometric sensors for the determination of a trinary anionic surfactant mixture.

An automated electronic tongue consisting of an array of potentiometric sensors and an artificial neural network (ANN) has been developed to resolve mixtures of anionic surfactants. The sensor array was formed by five different flow-through sensors for anionic surfactants, based on poly(vinyl chloride) membranes having cross-sensitivity features. Feedforward multilayer neural networks were used to predict surfactant concentrations. As a great amount of information is required for the correct modelling of the sensors response, a sequential injection analysis (SIA) system was used to automatically provide it. Dodecylsulfate (DS(-)), dodecylbenzenesulfonate (DBS(-)) and alpha-alkene sulfonate (ALF(-)) formed the three-analyte study case resolved in this work. Their concentrations varied from 0.2 to 4mM for ALF(-) and DBS(-) and from 0.2 to 5mM for DS(-). Good prediction ability was obtained with correlation coefficients better than 0.933 when the obtained values were compared with those expected for a set of 16 external test samples not used for training.

Report from the 'One Health' 9th Tick and Tick-Borne Pathogen Conference and the 1st Asia-Pacific Rickettsia Conference, Cairns, Australia, 27th August-1st September 2017.

The 9th Tick and Tick-borne Pathogen (TTP9) Conference was held in conjunction with the first Asia Pacific Rickettsia Conference (APRC1) in Cairns, Australia from 27 August until 1 September in 2017. This MDPI Veterinary Sciences Special Issue has been dedicated to selected veterinary science articles from the conference associated with the control of animal diseases in the context of ticks and tick-borne pathogens, including Rickettsia species. The articles presented in this Special Issue include novel developments for the future control of ticks and tick-borne diseases. This editorial describes the meeting content, the plenaries, the TTP awards, the MDPI Veterinary Science Special Issue articles, and serves as a legacy report for TTP9APRC1.

Anti-tick vaccines in the omics era.

Tick vaccines have been available for more than 20 years. They are useful and effective control agents when used properly. However, no new products have emerged since the Bm86-based Gavac vaccine was commercialized. Acaricide resistance is a problem with no abatement in sight and anti-tick vaccines are likely to be relied upon even more in the coming years. As human medicine and plant agriculture has embraced the various Omics technologies, the search for anti-tick vaccines would be well served to follow; so that new vaccine antigens and adjuvants might be developed to assist tick control programs. However, the simple outward appearance of ticks and their life cycle belies the complexity of their genomes which are computationally challenging to sequence and annotate. We review various Omics research efforts in light of research on anti-tick vaccines.

Ischemic Heart Disease during Acute Exacerbations of COPD.

Patients with chronic obstructive pulmonary disease (COPD) have a higher risk of acute cardiovascular events, and around 30% die from cardiovascular diseases. Recent data suggest an increased risk of myocardial infarction in the following days of a severe exacerbation of COPD. Disruption in the balance during the exacerbation with tachycardia, increased inflammation and systemic oxidative stress as well as some other factors may confer an increased risk of subsequent cardiovascular events. A number of investigations may be useful to an early diagnosis, including electrocardiography, imaging techniques and blood test for biomarkers. Some drugs that have changed prognosis in the cardiovascular setting such as cardioselective beta-blockers may be underused in patients with COPD despite its demonstrated benefits. This review focuses on several aspects of exacerbation of COPD and cardiovascular events including epidemiology, possible mechanism, diagnosis and treatment.