Regulation by anti-inflammatory cytokines (IL-4, IL-10, IL-13, TGFβ)of interleukin-8 production by LPS- and/ or TNFα-activated human polymorphonuclear cells

The capacity to down-regulate the production of IL-8 by LPS-activated human polymorphonuclear cells (PMN) has been demonstrated for IL-4, IL-10, and TGFβ. We compared their relative capacities and further extended this property to IL-13. We report a great heterogeneity among individuals related to the responsiveness of PMN to the IL-4 and IL-13 inhibitory effects while their response to the IL-10 effect was homogenous. The inhibitory activities were observed at the transcriptional level. IL-8 induction by TNFα was, unlike its induction by LPS, resistant to the inhibitory effects of IL-10, IL-4, IL-13 and TGFβ. Furthermore, IL-10 and IL-4 inhibitory activity were less effective when TNFα was acting synergistically with LPS to induce IL-8 production by PMN. LPS-induced cell-associated IL-8, detected in the PMN cultures, could be marginally inhibited by IL-4 and IL-10. Altogether, our data demonstrate that IL-13 is able to inhibit LPS-induced IL-8 production by human PMN, although IL-10 remains the most active anti-inflammatory cytokine. Despite the capacity of IL-4, IL-10, and IL-13 to limit the production of TNFα-induced IL-8 in a whole blood assay, none was able to inhibit this production when studying isolated human polymorphonuclear cells

Synthesis and characterisation of peroxypinic acids as proxies for highly oxygenated molecules (HOMs) in secondary organic aerosol

Peroxy acids were recently found to be involved in new particle formation in the atmosphere and could also substantially contribute towards particle toxicity. However, a lack of suitable analytical methods for the detection and characterisation of peroxy acids in the particle phase is currently hindering the quantitative investigation of their contribution to these important atmospheric processes. Further development of appropriate techniques and relevant standards is therefore urgently needed. In this study, we synthesised three peroxypinic acids, developed a liquid chromatography separation method and characterised them with tandem mass spectrometry. The observed fragmentation patterns clearly distinguish the different peroxypinic acids from both the acid and each other, showing several neutral losses previously already observed for other peroxy acids. Both monoperoxypinic acids were found to be present in secondary organic aerosol generated from ozonolysis of α-pinene in laboratory experiments. The yield of monoperoxypinic acid formation was not influenced by humidity. Monoperoxypinic acid quickly degrades on the filter, with about 60% lost within the first 5h. This fast degradation shows that time delays in traditional off-line analysis will likely lead to severe underestimates of peroxy compound concentrations in ambient particles.Sarah S. Steimer acknowledges funding support from the Swiss National Science Foundation (project no. 162258). Funding by the European Research Council (ERC starting grant 279405) and the European Union’s Horizon 2020 research and innovation programme through the EUROCHAMP-2020 Infrastructure Activity under grant agreement no. 730997 is acknowledged

Spatial structure of shock formation

The formation of a singularity in a compressible gas, as described by the Euler equation, is characterized by the steepening and eventual overturning of a wave. Using self-similar variables in two space dimensions and a power series expansion based on powers of , being the singularity time, we show that the spatial structure of this process, which starts at a point, is equivalent to the formation of a caustic, i.e. to a cusp catastrophe. The lines along which the profile has infinite slope correspond to the caustic lines, from which we construct the position of the shock. By solving the similarity equation, we obtain a complete local description of wave steepening and of the spreading of the shock from a point. The shock spreads in the transversal direction as and in the direction of propagation as , as also found in a one-dimensional model problem

Parallel Evolution of Pseudomonas aeruginosa during a Prolonged ICU-Infection Outbreak.

Most knowledge about Pseudomonas aeruginosa pathoadaptation is derived from studies on airway colonization in cystic fibrosis; little is known about adaptation in acute settings. P. aeruginosa frequently affects burned patients and the burn wound niche has distinct properties that likely influence pathoadaptation. This study aimed to genetically and phenotypically characterize P. aeruginosa isolates collected during an outbreak of infection in a burn intensive care unit (ICU). Sequencing reads from 58 isolates of ST1076 P. aeruginosa taken from 23 patients were independently mapped to a complete reference genome for the lineage (H25338); genetic differences were identified and were used to define the population structure. Comparative genomic analysis at single-nucleotide resolution identified pathoadaptive genes that evolved multiple, independent mutations. Three key phenotypic assays (growth performance, motility, carbapenem resistance) were performed to complement the genetic analysis for 47 unique isolates. Population structure for the ST1076 lineage revealed 11 evolutionary sublineages. Fifteen pathoadaptive genes evolved mutations in at least two sublineages. The most prominent functional classes affected were transcription/two-component regulatory systems, and chemotaxis/motility and attachment. The most frequently mutated gene was oprD, which codes for outer membrane porin involved in uptake of carbapenems. Reduced growth performance and motility were found to be adaptive phenotypic traits, as was high level of carbapenem resistance, which correlated with higher carbapenem consumption during the outbreak. Multiple prominent linages evolved each of the three traits in parallel providing evidence that they afford a fitness advantage for P. aeruginosa in the context of human burn infection. IMPORTANCE Pseudomonas aeruginosa is a Gram-negative pathogen causing infections in acutely burned patients. The precise mechanisms required for the establishment of infection in the burn setting, and adaptive traits underpinning prolonged outbreaks are not known. We have assessed genotypic data from 58 independent P. aeruginosa isolates taken from a single lineage that was responsible for an outbreak of infection in a burn ICU that lasted for almost 2.5 years and affected 23 patients. We identified a core set of 15 genes that we predict to control pathoadaptive traits in the burn infection based on the frequency with which independent mutations evolved. We combined the genotypic data with phenotypic data (growth performance, motility, antibiotic resistance) and clinical data (antibiotic consumption) to identify adaptive phenotypes that emerged in parallel. High-level carbapenem resistance evolved rapidly, and frequently, in response to high clinical demand for this antibiotic class during the outbreak

Mutation to ispA Produces Stable Small-Colony Variants of Pseudomonas aeruginosa That Have Enhanced Aminoglycoside Resistance.

Pseudomonas aeruginosa is a major pathogen in burn wound infections. We present one of the first reports of small-colony variant (SCV) emergence of P. aeruginosa, taken from a patient under aminoglycosides for a persistent burn wound infection. We confirm the causative role of a single ispA mutation in SCV emergence and increased aminoglycoside resistance. IspA is involved in the synthesis of ubiquinone, providing a possible link between electron transport and SCV formation in P. aeruginosa

Prevención del dolor musculoesquelético en trabajadores de dos establecimientos hortícolas, en la provincia de Corrientes, Argentina

There is no previous researchwork as regards Musculoskeletal Disorders (MSD) in horticultural workers from Lavalle, Corrientes. The aims were to estimate the prevalence of MSD in the spine and shoulders, the physical effort of seedling transplant activity and the impact of preventive exercises in a population of intensive horticulture workers. A controlled and prospective clinical  trial study was carried out in three groups, two intervention groups A – B, for 12 months and a comparative group, C, for 6 months. The lifetime prevalence of punctual, quaterly and annual pain in cervical spine, thoracic, lumbar and shoulders, was analyzed at the beginning, at 3, 6, 9 and 12 months in the intervention groups A and B. In group C, at the beginning, at 3 and 6 months. The most prevalent MSD was low back pain 98%, 94.3% and 66.7%, followed by dorsal pain 61.7%, 52.7% and 55.3%; cervical pain 61%, 45% and 55.3%; and, shoulders pain 54%, 40.3% and 35%, (average lifetime, annual and punctual prevalence of the 3 groups A, B and C, respectively). Once the preventive strategies were implemented, low back pain decreased by 60% and 100% in the intervention groups; 33% in the comparative, back pain, 59.8% and 100%, in the intervention groups, and 25.4% in group C, neck pain, was reduced 87%, 100% and 0%, in intervention groups A, B and control C group, respectively. Shoulder pain fell 76% in the intervention group and 34% in the comparison group C. The transplant activity was characterized as "light" and "heavy", morning and afternoon, respectively. Low back pain is the most prevalent MSD. Prevention strategies, based on the combination of training and specific physical exercises, allowed to reduce pain in intensive horticulture workers.No existen antecedentes de estimación de prevalencias de dolencias físicas en trabajadores hortícolas de Lavalle, Corrientes. Objetivos: estimar la prevalencia de los Desórdenes Músculo-Esqueléticos (DME) en la columna vertebral y hombros, el esfuerzo físico de la actividad de trasplante de plantines y el impacto de ejercicios preventivos en una población de trabajadores de horticultura intensiva. Se realizó un ensayo clínico – controlado, prospectivo en tres grupos, dos de intervención A – B, por un período de 12 meses y un grupo comparativo C, 6 meses de duración. Se analizó, la prevalencia de vida, anual, trimestral y puntual de dolencias, en columna cervical, dorsal, lumbar y hombros, al inicio, 3, 6, 9 y 12 meses en los grupos de intervención A y B. En el grupo C, al inicio, 3 y 6 meses. La dolencia más prevalente, fue el dolor lumbar 98 %, 94,3 % y 66,7 %, seguida por el dorsal 61,7 %, 52,7 % y 55,3 %; cervical 61 %, 45 % y 55,3 %; hombros 54 %, 40,3 % y 35 % (prevalencias de vida, anual y puntual promedio de los 3 grupos A, B y C). Implementadas las estrategias preventivas, el dolor lumbar bajo un 60 % y 100 % en los grupos de intervención; 33 % en el comparativo, el dolor dorsal, 59,8 % y 100 %, en los grupos de intervención, y 25,4% en el grupo C, el dolor cervical, se redujo 87 %, 100 % y 0 %, en los grupos de intervención, A, B y en el control C, respectivamente. El dolor de hombros, cayó un 76 % en el de intervención y 34% en el grupo comparativo. La actividad de trasplante, se caracterizó como “ligera” y “pesada”, mañana y tarde, respectivamente  El dolor lumbar es el DME, más prevalente. Estrategias de prevención, basadas en la combinación de capacitación y ejercicios físicos específicos, permiten reducir las dolencias en trabajadores de horticultura intensiva

MosChito rafts as effective and eco-friendly tool for the delivery of a Bacillus thuringiensis-based insecticide to Aedes albopictus larvae

Adult mosquito females, through their bites, are responsible for the transmission of different zoonotic pathogens. Although adult control represents a pillar for the prevention of disease spread, larval control is also crucial. Herein we characterized the effectiveness of a suitable tool, named "MosChito raft", for the aquatic delivery of a Bacillus thuringiensis var. israelensis (Bti) formulate, a bioinsecticide active by ingestion against mosquito larvae. MosChito raft is a floating tool composed by chitosan cross-linked with genipin in which a Bti-based formulate and an attractant have been included. MosChito rafts (i) resulted attractive for the larvae of the Asian tiger mosquito Aedes albopictus, (ii) induced larval mortality within a few hours of exposure and, more importantly, (iii) protected the Bti-based formulate, whose insecticidal activity was maintained for more than one month in comparison to the few days residual activity of the commercial product. The delivery method was effective in both laboratory and semi-field conditions, demonstrating that MosChito rafts may represent an original, eco-based and user-friendly solution for larval control in domestic and peri-domestic aquatic habitats such as saucers and artificial containers in residential or urban environments

Efficacy assessment of a novel endolysin PlyAZ3aT for the treatment of ceftriaxone-resistant pneumococcal meningitis in an infant rat model.

BACKGROUND Treatment failure in pneumococcal meningitis due to antibiotic resistance is an increasing clinical challenge and alternatives to antibiotics warrant investigation. Phage-derived endolysins efficiently kill gram-positive bacteria including multi-drug resistant strains, making them attractive therapeutic candidates. The current study assessed the therapeutic potential of the novel endolysin PlyAZ3aT in an infant rat model of ceftriaxone-resistant pneumococcal meningitis. METHODS Efficacy of PlyAZ3aT was assessed in a randomized, blinded and controlled experimental study in infant Wistar rats. Meningitis was induced by intracisternal infection with 5 x 107 CFU/ml of a ceftriaxone-resistant clinical strain of S. pneumoniae, serotype 19A. Seventeen hours post infection (hpi), animals were randomized into 3 treatment groups and received either (i) placebo (phosphate buffered saline [PBS], n = 8), (ii) 50 mg/kg vancomycin (n = 10) or (iii) 400 mg/kg PlyAZ3aT (n = 8) via intraperitoneal injection. Treatments were repeated after 12 h. Survival at 42 hpi was the primary outcome; bacterial loads in cerebrospinal fluid (CSF) and blood were secondary outcomes. Additionally, pharmacokinetics of PlyAZ3aT in serum and CSF was assessed. RESULTS PlyAZ3aT did not improve survival compared to PBS, while survival for vancomycin treated animals was 70% which is a significant improvement when compared to PBS or PlyAZ3aT (p<0.05 each). PlyAZ3aT was not able to control the infection, reflected by the inability to reduce bacterial loads in the CSF, whereas Vancomycin sterilized the CSF and within 25 h. Pharmacokinetic studies indicated that PlyAZ3aT did not cross the blood brain barrier (BBB). In support, PlyAZ3aT showed a peak concentration of 785 μg/ml in serum 2 h after intraperitoneal injection but could not be detected in CSF. CONCLUSION In experimental pneumococcal meningitis, PlyAZ3aT failed to cure the infection due to an inability to reach the CSF. Optimization of the galenic formulation e.g. using liposomes might enable crossing of the BBB and improve treatment efficacy

Research Trends on Preventive and Therapeutic Use of TIF4 for Dental Caries and Erosion

Objective: To evaluate TIF4 preventive and therapeutic use in caries and erosive lesions. Material and Methods: Searches were performed in six databases. Studies evaluating TiF4 use in vitro, in situ, and in vivo in caries and erosive lesions were included and imported into VantagePoint™ (VP). Data about publication year, authors, country, journal, study design, outcomes, TIF4 vehicles, application and intervention time, cariogenic challenge, erosive cycles, effects (positive/ negative /null) and approach (preventive/therapeutic) were analyzed through VP and Excel. Results: 93 published studies were included and an increase in publications was observed between 2010 and 2021. Forty-three authors published three or more articles, of which 67.4% were developed in Brazil and published in Caries Research (22.6%). 69.9% were in vitro studies with erosion assays (59.1%) and with preventive approaches (67.4%). The principal vehicle was a solution (69.9%) with a 1-min single application (58.0%) and with an intervention time of 5-7 days (22.6%). The principal cariogenic challenge in vitro was pH cycling (11.8%); in situ was sucrose + biofilm (6.2%); and in vivo, biofilm (6.2%). The most used erosive cycle was 4× per day in in vitro studies (20.4%) and 1× in vivo (2.1%). A positive effect was observed in prevention (41.9%) and treatment (24.7%) studies. Conclusion: TIF4 has shown a positive effect in prevention and therapeutic treatments for dental caries and erosion