Phagosomal granulocytic ROS in septic patients induce the bacterial SOS response.

Septic patients with worst clinical prognosis have increased circulating immature granulocytes (IG), displaying limited phagocytosis and reactive oxygen species (ROS) production. Here, we developed an ex vivo model of incubation of human granulocytes, from septic patients or healthy donors, with Escherichia coli. We showed that the ROS production in Sepsis-IG is lower due to decreased activation and protein expression of the NADPH oxidase complex. We also demonstrated that the low level of ROS production and lower phagocytosis of IG in sepsis induce the bacterial SOS response, leading to the expression of the SOS-regulated quinolone resistance gene qnrB2. Without antimicrobial pressure, the sepsis immune response alone may promote antibiotic resistance expression.

Construction of a Mycoviral Infectious Clone for Reverse Genetics in Botrytis cinerea.

The most important advances in our understanding of the viral life cycle, such as genome replication, packaging, transmission, and host interactions, have been made via the development of viral infectious full-length clones. Here, we describe the detailed protocols for the construction of an infectious clone derived from Botrytis virus F (BVF), a mycoflexivirus infecting the plant pathogenic fungus Botrytis cinerea, the determination of the complete sequence of the cloned mycovirus, the preparation of fungal protoplasts, and the transfection of protoplasts using transcripts derived from the BVF infectious clone.

SARS-CoV-2 infection and long COVID among California farmworkers.

PURPOSE: The purpose of this cross-sectional study was to determine the prevalence of long COVID and identify its clinical manifestations among farmworkers in California. METHODS: We collected data on sociodemographic characteristics, anthropometrics, clinical chemistries and anti-SARS-CoV-2 immunoglobulin G antibodies, self-reported SARS-CoV-2 infection history, and standardized health tests and scales from 297 farmworkers in California between February and July 2022. RESULTS: Most participants were born in Mexico or Central America, had less than a high school diploma, and were overweight or obese. The prevalence of long COVID (defined as self-reported SARS-CoV-2 infection with symptoms >28 days) among farmworkers with a suspected or test-confirmed infection was 61.8%. Participants with long COVID had higher mean [95% CI] body mass index (32.9 [31.6-34.1]) and high-sensitivity C-reactive protein levels (4.8 [3.7, 6.0]) than those with no COVID-19 history (30.5 [29.3-31.7], and 3.3 [2.2, 4.3], respectively). Farmworkers with long COVID also reported greater fatigue, dyspnea, taste and smell problems, and overall poorer mental and physical health, than those with no COVID-19 history. Farmworkers with long COVID had increased odds of functional limitations compared to those with a self-reported SARS-CoV-2 infection with symptoms ≤28 days (OR [95% CI]: 7.46 [3.26, 17.09]). CONCLUSIONS: A significant proportion of farmworkers experience long COVID with persistent symptoms that limit their ability to perform their work. A comprehensive approach that addresses the unique needs and challenges of farmworkers is warranted given this population's high prevalence of long COVID and the essential nature of their work.

Determination of the Mycovirome of a Necrotrophic Fungus.

Next-generation sequencing (NGS) of total RNA has allowed the detection of novel viruses infecting different hosts, such as fungi, increasing our knowledge on virus horizontal transfer events among different hosts, virus diversity, and virus evolution. Here, we describe the detailed protocols for the isolation of the plant pathogenic fungus Botrytis cinerea, from grapevine plants showing symptoms of the mold gray disease, the culture and maintenance of the isolated B. cinerea strains, the extraction of total RNA from B. cinerea strains for NGS, the bioinformatics pipeline designed and followed to detect mycoviruses in the sequenced samples, and the validation of the in silico detected mycoviruses by different approaches.

Molecular characterization of a tetra segmented ssDNA virus infecting Botrytis cinerea worldwide.

BACKGROUND: Family Genomoviridae was recently established, and only a few mycoviruses have been described and characterized, and almost all of them (Sclerotinia sclerotiorum hypovirulence-associated DNA virus 1, Fusarium graminearum gemyptripvirus 1 and Botrytis cinerea gemydayirivirus 1) induced hypovirulence in their host. Botrytis cinerea ssDNA virus 1 (BcssDV1), a tetrasegmented single-stranded DNA virus infecting the fungus Botrytis cinerea, has been molecularly characterized in this work. METHODS: BcssDV1 was detected in Spanish and Italian B. cinerea field isolates obtained from grapevine. BcssDV1 variants genomes were molecularly characterized via NGS and Sanger sequencing. Nucleotide and amino acid sequences were used for diversity and phylogenetic analysis. Prediction of protein tertiary structures and putative associated functions were performed by AlphaFold2 and DALI. RESULTS: BcssDV1 is a tetrasegmented single-stranded DNA virus. The mycovirus was composed by four genomic segments of approximately 1.7 Kb each, which are DNA-A, DNA-B, and DNA-C and DNA-D, that coded, respectively, for the rolling-circle replication initiation protein (Rep), capsid protein (CP) and two hypothetical proteins. BcssDV1 was present in several Italian and Spanish regions with high incidence and low variability among the different viral variants. DNA-A and DNA-D were found to be the more conserved genomic segments among variants, while DNA-B and DNA-C segments were shown to be the most variable ones. Tertiary structures of the proteins encoded by each segment suggested specific functions associated with each of them. CONCLUSIONS: This study presented the first complete sequencing and characterization of a tetrasegmented ssDNA mycovirus, its incidence in Spain and Italy, its presence in other countries and its high conservation among regions.

Co-exposure to pathogens in wild ungulates from Doñana National Park, South Spain.

Multiple infections or co-exposure to pathogens should be considered systematically in wildlife to better understand the ecology and evolution of host-pathogen relationships, so as to better determine the potential use of multiple pathogens as indicators to guide health management. We describe the pattern of co-exposure to several pathogens (i.e. simultaneous positive diagnosis to pathogens in an individual considering Mycobacterium tuberculosis complex lesions, and the presence of antibodies against Toxoplasma gondii, bluetongue virus, and hepatitis E virus) and assessed their main drivers in the wild ungulate community from Doñana National Park (red deer, fallow deer, and wild boar) for a 13-years longitudinal study. The lower-than-expected frequency of co-exposure registered in all species was consistent with non-mutually exclusive hypotheses (e.g. antagonism or disease-related mortality), which requires further investigation. The habitat generalist species (red deer and wild boar) were exposed to a greater diversity of pathogens (frequency of co-exposure around 50%) and/or risk factors than fallow deer (25.0% ± CI95% 4.9). Positive relationships between pathogens were evidenced, which may be explained by common risk factors favouring exposure. The specific combination of pathogens in individuals was mainly driven by different groups of factors (individual, environmental, stochastic, and populational), as well as its interaction, defining a complex eco-epidemiological landscape. To deepen into the main determinants and consequences of co-infections in a complex assemblage of wild hosts, and at the interface with humans and livestock, there also is needed to expand the range of pathogens and compare diverse assemblages of hosts under different environmental and management circumstances.

Living donor liver paired exchange between pediatric and adult recipients due to donor graft size mismatch.

Living donor liver transplantation is an effective means to decrease organ shortage. However, many potential living donors are currently being denied due to ABO incompatibility or inadequate donor liver volume. Liver paired exchange (LPE) provides a practical solution to overcome these obstacles, and yet the first case of LPE in the United States was only recently reported in 2020. Here, we report world's first case of LPE involving pediatric and adult recipients to avoid surgical complexity of the pediatric recipient and to increase the graft-to-recipient weight ratio of the adult recipient between 2 ABO compatible pairs. As living donor liver transplantation becomes more widely adopted, the need for pair exchange to improve surgical safety and postoperative outcomes between 2 ABO compatible pairs is likely to increase.

Leucoencefalopatía multifocal progresiva: enfermedad grave en el paciente inmunosuprimido. Reporte de caso / Progressive multifocal leukoencephalopathy: severe disease in the immunosuppressed patient. Case report

RESUMEN INTRODUCCIÓN: Los pacientes con compromiso del sistema inmune pueden desarrollar una enfermedad neurológica incapacitante e incluso mortal, como lo es la leucoencefalopatía multifocal progresiva (LMP) producida por el virus de John Cunningham (JC). PRESENTACIÓN DEL CASO: Se presenta el caso de un hombre de 26 años con diagnóstico reciente de infección por virus de la inmunodeficiencia humana (VIH) que presentó síntomas constitucionales, déficit neurológico progresivo por hemiparesia espástica izquierda, disminución de la agudeza visual y cambios comportamentales. En las imágenes de resonancia magnética (IRM) cerebral contrastada se encontró afectación subcortical difusa de la sustancia blanca con compromiso de las fibras en U que, correlacionado con una prueba de reacción en cadena de la polimerasa (PCR) para virus JC en LCR, confirmó el diagnóstico de LMP. DISCUSIÓN: La LMP puede manifestarse por medio de síntomas cognitivos usualmente imperceptibles para el clínico, pero también como déficit sensorio-motor y visual que se puede corroborar en las IRM al identificar las lesiones típicas en la sustancia blanca, o bien por medio de detección del virus por PCR en líquido cefalorraquídeo. El manejo específico de la causa que desencadenó la inmunosupresión sigue siendo el pilar de tratamiento. CONCLUSIÓN: La mínima sospecha diagnóstica en aquellos pacientes con factores de riesgo y manifestaciones clínicas concordantes con la enfermedad debe llevar a que se confirme el diagnóstico y que se inicie prontamente el manejo terapéutico en búsqueda de restablecer la respuesta inmune.

ABSTRACT INTRODUCTION: Patients with immunocompromised or weakened immune system can develop a disabling and even life-threatening neurological disorder such as progressive multifocal leukoencephalopathy (PML) caused by John Cunningham (JC) virus. CASE PRESENTATION: We present the case of a 26-year-old man with a recent diagnosis of human immunodeficiency virus (HIV) infection who presented constitutional symptoms, progressive neurological deficit due to left spastic hemiparesis with decreased visual acuity and behavioral changes. The brain Magnetic Resonance Imaging (MRI) showed diffuse subcortical involvement of the white matter including the U-fibers, which, correlated with a detection of JC virus DNA by polymerase chain reaction (PCR) cerebrospinal fluid, confirmed the diagnosis of PML. DISCUSSION: PML can range from subtle cognitive impairment imperceptible to the clinician to sensory-motor deficits and visual disturbances that can be corroborated in MRI by identifying the typical lesions in the white matter or by detecting the virus by PCR in cerebrospinal fluid. The specific management of the cause that triggered the immunosuppression continues to be the mainstay of treatment. CONCLUSION: At the minimum diagnostic suspicion in patients with risk factors and clinical manifestations consistent with the disease should proceed to confirm the diagnosis and promptly immune reconstitution.

Performance of the Cepheid Methicillin-Resistant Staphylococcus aureus/S. aureus Skin and Soft Tissue Infection PCR Assay on Respiratory Samples from Mechanically Ventilated Patients for S. aureus Screening during the Phase 2 Double-Blind SAATELLITE Study.

We investigated the performance of the Xpert methicillin-resistant Staphylococcus aureus (MRSA)/S. aureus skin and soft tissue (SSTI) quantitative PCR (qPCR) assay in SAATELLITE, a multicenter, double-blind, phase 2 study of suvratoxumab, a monoclonal antibody (MAb) targeting S. aureus alpha-toxin, for reducing the incidence of S. aureus pneumonia. The assay was used to detect methicillin-susceptible S. aureus (MSSA) and MRSA in lower respiratory tract (LRT) samples from mechanically ventilated patients. LRT culture results were compared with S. aureus protein A (spa) gene cycle threshold (CT) values. Receiver operating characteristic (ROC) and Youden index were used to determine the CT cutoff for best separation of culture-S. aureus-negative and S. aureus-positive patients. Of 720 screened subjects, 299 (41.5%) were S. aureus positive by qPCR, of whom 209 had culture data: 162 (77.5%) were S. aureus positive and 47 (22.5%) were S. aureus negative. Culture results were negatively affected by antibiotic use and cross-laboratory variability. An inverse linear correlation was observed between CT values and quantitative S. aureus culture results. A spa CT value of 29 (≈2 × 103 CFU/mL) served as the best cutoff for separation between culture-negative and culture-positive samples. The associated area under the ROC curve was 83.8% (95% confidence interval [CI], 78 to 90%). Suvratoxumab provided greater reduction in S. aureus pneumonia or death than placebo in subjects with low S. aureus load (CT ≥ 29; relative risk reduction [RRR], 50.0%; 90% CI, 2.7 to 74.4%) versus the total study population (RRR, 25.2%; 90% CI, -4.3 to 46.4%). The qPCR assay was easy to perform, sensitive, and standardized and provided better sensitivity than conventional culture for S. aureus detection. Quantitative PCR CT output correlated with suvratoxumab efficacy in reducing S. aureus pneumonia incidence or death in S. aureus-colonized, mechanically ventilated patients.

Construction and Characterization of a Botrytis Virus F Infectious Clone.

Botrytis virus F (BVF) is a positive-sense, single-stranded RNA (+ssRNA) virus within the Gammaflexiviridae family of the plant-pathogenic fungus Botrytis cinerea. In this study, the complete sequence of a BVF strain isolated from B. cinerea collected from grapevine fields in Spain was analyzed. This virus, in this work BVF-V448, has a genome of 6827 nt in length, excluding the poly(A) tail, with two open reading frames encoding an RNA dependent RNA polymerase (RdRP) and a coat protein (CP). The 5'- and 3'-terminal regions of the genome were determined by rapid amplification of cDNA ends (RACE). Furthermore, a yet undetected subgenomic RNA species in BVF-V448 was identified, indicating that the CP is expressed via 3' coterminal subgenomic RNAs (sgRNAs). We also report the successful construction of the first BVF full-length cDNA clone and synthesized in vitro RNA transcripts using the T7 polymerase, which could efficiently transfect two different strains of B. cinerea, B05.10 and Pi258.9. The levels of growth in culture and virulence on plants of BVF-V448 transfected strains were comparable to BVF-free strains. The infectious clones generated in this work provide a useful tool for the future development of an efficient BVF foreign gene expression vector and a virus-induced gene silencing (VIGS) vector as a biological agent for the control of B. cinerea.

High prevalence of infections in non-COVID-19 patients admitted to the Emergency Department with severe lymphopenia.

BACKGROUND: In the Emergency Department (ED), early and accurate recognition of infection is crucial to prompt antibiotic therapy but the initial presentation of patients is variable and poorly characterized. Lymphopenia is commonly associated with bacteraemia and poor outcome in intensive care unit patients. The objective of this retrospective study was to assess the prevalence of community-acquired infection in a cohort of unselected patients admitted to the ED with undifferentiated symptoms and severe lymphopenia. METHODS: This is a retrospective single-center study conducted over a 1 year-period before the COVID-19 pandemic. Consecutive adult patients admitted to the ED with severe lymphopenia (lymphocyte count < 0.5 G/L) were studied. Patients with hematological or oncological diseases, HIV infection, hepato-cellular deficiency, immunosuppression, or patients over 85 years old were excluded. Diagnoses of infection were validated by an independent adjudication committee. The association between various parameters and infection was assessed using a multivariate logistic regression analysis. RESULTS: Of 953 patients admitted to the ED with severe lymphopenia, 245 were studied (148 men; mean age: 63 ± 19 years). Infection was confirmed in 159 patients (65%) (bacterial: 60%, viral: 30%, other: 10%). Only 61 patients (25%) were referred to the ED for a suspected infection. In the univariate analysis, SIRS criteria (OR: 5.39; 95%CI: 3.04-9.70; p < 0.001) and temperature ≥ 38.3 °C (OR: 10.95; 95%CI: 5.39-22.26; p < 0.001) were strongly associate with infection. In the multivariate analysis, only SIRS criteria (OR: 2.4; 95%CI: 1.48-3.9; p < 0.01) and fever (OR: 3.35; 95%CI: 1.26-8.93; p = 0.016) were independently associated with infection. CONCLUSIONS: The prevalence of underlying infection is high in patients admitted to the ED with lymphopenia, irrespective of the reason for admission. Whether lymphopenia could constitute a valuable marker of underlying infection in this clinical setting remains to be confirmed prospectively in larger cohorts. TRIAL REGISTRATION: No registration required as this is a retrospective study.

Strategy of Nematophagous Fungi in Determining the Activity of Plant Parasitic Nematodes and Their Prospective Role in Sustainable Agriculture.

In this review, we supply a framework for the importance of nematophagous fungi (nematophagous fungi [NF]) and their role in agricultural ecosystems. We characterize the taxonomy, diversity, ecology, and type of NF, depending on their interaction with plant-parasitic nematodes (PPNs). We described potential mechanisms of NF in the control of PPNs, the efficiency and methods of utilization, and the use of nematicides in sustainable agriculture. We explain the utilization of NF in nanotechnology as a new approach. NF are significant in the soil for having the effective potential for use in sustainable agriculture. These types of fungi belong to wide taxa groups, such as Ascomycota, Basidiomycota, and other groups. Diverse NF are available in different kinds of soil, especially in soils that contain high densities of nematodes. There is a relationship between the environment of nematodes and NF. NF can be divided into two types according to the mechanisms that affect nematodes. These types are divided into direct or indirect effects. The direct effects include the following: ectoparasites, endoparasites, cyst, or egg parasites producing toxins, and attack tools as special devices. However, the indirect effect comprises two groups: paralyzing toxins and the effect on the life cycle of nematodes. We explained the molecular mechanisms for determining the suitable conditions in brief and clarified the potential for increasing the efficacy of NF to highly impact sustainable agriculture in two ways: directly and indirectly.

Immature granulocytes can help the diagnosis of pulmonary bacterial infections in patients with severe COVID-19 pneumonia.

During COVID-19, immature granulocyte (IG) concentration is heterogeneous with higher concentrations than those found in bacterial sepsis. We investigated the relationship between IG levels at ICU admission and on days 7 (± 2) and 15 (± 2) and associated pulmonary bacterial infections in intensive care unit (ICU) patients hospitalized for an acute respiratory distress syndrome (ARDS) related to SARS-CoV-2. Patients with associated pulmonary bacterial infection had a peak of IGs. IG thresholds of 18% or 2 G/L allowed discriminating patients with ventilator associated pneumonia with 100% sensitivity and specificity. Our study supports that IGs could help identifying pulmonary bacterial infections in this population.

Novel Mycoviruses Discovered in the Mycovirome of a Necrotrophic Fungus.

Botrytis cinerea is one of the most important plant-pathogenic fungus. Products based on microorganisms can be used in biocontrol strategies alternative to chemical control, and mycoviruses have been explored as putative biological agents in such approaches. Here, we have explored the mycovirome of B. cinerea isolates from grapevine of Italy and Spain to increase the knowledge about mycoviral diversity and evolution, and to search for new widely distributed mycoviruses that could be active ingredients in biological products to control this hazardous fungus. A total of 248 B. cinerea field isolates were used for our metatranscriptomic study. Ninety-two mycoviruses were identified: 62 new mycoviral species constituting putative novel viral genera and families. Of these mycoviruses, 57 had a positive-sense single-stranded RNA (ssRNA) genome, 19 contained a double-stranded RNA (dsRNA) genome, 15 had a negative-sense ssRNA genome, and 1 contained a single-stranded DNA (ssDNA) genome. In general, ssRNA mycoviruses were widely distributed in all sampled regions, the ssDNA mycovirus was more frequently found in Spain, and dsRNA mycoviruses were scattered in some pools of both countries. Some of the identified mycoviruses belong to clades that have never been found associated with Botrytis species: Botrytis-infecting narnaviruses; alpha-like, umbra-like, and tymo-like ssRNA+ mycoviruses; trisegmented ssRNA- mycovirus; bisegmented and tetrasegmented dsRNA mycoviruses; and finally, an ssDNA mycovirus. Among the results obtained in this massive mycovirus screening, the discovery of novel bisegmented viruses, phylogenetically related to narnaviruses, is remarkable.IMPORTANCE The results obtained here have expanded our knowledge of mycoviral diversity, horizontal transfers, and putative cross-kingdom events. To date, this study presents the most extensive and wide diversity collection of mycoviruses infecting the necrotrophic fungus B. cinerea The collection included all types of mycoviruses, with dsRNA, ssRNA+, ssRNA-, and ssDNA genomes, most of which were discovered here, and some of which were previously reported as infecting B. cinerea or other plant-pathogenic fungi. Some of these mycoviruses are reported for the first time here associated with B. cinerea, as a trisegmented ssRNA- mycovirus and as an ssDNA mycovirus, but even more remarkablly, we also describe here four novel bisegmented viruses (binarnaviruses) not previously described in nature. The present findings significantly contribute to general knowledge in virology and more particularly in the field of mycovirology.

Efficacy and safety of suvratoxumab for prevention of Staphylococcus aureus ventilator-associated pneumonia (SAATELLITE): a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial.

BACKGROUND: Staphylococcus aureus remains a common cause of ventilator-associated pneumonia, with little change in incidence over the past 15 years. We aimed to evaluate the efficacy of suvratoxumab, a monoclonal antibody targeting the α toxin, in reducing the incidence of S aureus pneumonia in patients in the intensive care unit (ICU) who are on mechanical ventilation. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial at 31 hospitals in Belgium, the Czech Republic, France, Germany, Greece, Hungary, Portugal, Spain, and Switzerland. Eligible patients were in the ICU, aged ≥18 years, were intubated and on mechanical ventilation, were positive for S aureus colonisation of the lower respiratory tract, as assessed by quantitative PCR (qPCR) analysis of endotracheal aspirate, and had not been diagnosed with new-onset pneumonia. Patients were excluded if they had confirmed or suspected acute ongoing staphylococcal disease; had received antibiotics for S aureus infection for more than 48 h within 72 h of randomisation; had a Clinical Pulmonary Infection Score of 6 or higher; had an acute physiology and chronic health evaluation II score of 25 or higher with a Glasgow coma scale (GCS) score of more than 5, or an acute physiology and chronic health evaluation II score of at least 30 with a GCS score of 5 or less; had a Sequential Organ Failure Assessment score of 9 or higher; or had active pulmonary disease that would impair the ability to diagnose pneumonia. Colonised patients were randomly assigned (1:1:1), by use of an interactive voice or web response system, to receive either a single intravenous infusion of suvratoxumab 2000 mg, suvratoxumab 5000 mg, or placebo. Randomisation was done in blocks of size four, stratified by country and by whether patients had received systemic antibiotics for S aureus infection. Patients, investigators, and study staff involved in the treatment or clinical evaluation of patients were masked to patient assignment. The primary efficacy endpoint was the incidence of S aureus pneumonia at 30 days, as determined by a masked independent endpoint adjudication committee, in all patients who received their assigned treatment (modified intention-to-treat [ITT] population). Primary safety endpoints were the incidence of treatment-emergent adverse events at 30 days, 90 days, and 190 days after treatment, and the incidence of treatment-emergent serious adverse events, adverse events of special interest, and new-onset chronic disease at 190 days after treatment. All primary safety endpoints were assessed in the modified ITT population. This trial is registered with ClinicalTrials.gov (NCT02296320) and the EudraCT database (2014-001097-34). FINDINGS: Between Oct 10, 2014, and April 1, 2018, 767 patients were screened, of whom 213 patients with confirmed S aureus colonisation of the lower respiratory tract were randomly assigned to the suvratoxumab 2000 mg group (n=15), the suvratoxumab 5000 mg group (n=96), or the placebo group (n=102). Two patients in the placebo group did not receive treatment after randomisation because their clinical conditions changed and they no longer met the eligibility criteria for dosing. As adjudicated by the data monitoring committee at an interim analysis, the suvratoxumab 2000 mg group was discontinued on the basis of predefined pharmacokinetic criteria. At 30 days after treatment, 17 (18%) of 96 patients in the suvratoxumab 5000 mg group and 26 (26%) of 100 patients in the placebo group had developed S aureus pneumonia (relative risk reduction 31·9% [90% CI -7·5 to 56·8], p=0·17). The incidence of treatment-emergent adverse events at 30 days were similar between the suvratoxumab 5000 mg group (87 [91%]) and the placebo group (90 [90%]). The incidence of treatment-emergent serious adverse events at 30 days were also similar between the suvratoxumab 5000 mg group (36 [38%]) and the placebo group (32 [32%]). No significant difference in the incidence of treatment-emergent adverse events between the two groups at 90 days (89 [93%] in the suvratoxumab 5000 mg group vs 92 [92%] in the placebo group) and at 190 days (93 [94%] vs 93 [93%]) was observed. 40 (40%) patients in the placebo group and 50 (52%) in the suvratoxumab 5000 mg group had a serious adverse event at 190 days. In the suvratoxumab 5000 mg group, one (1%) patient reported at least one treatment-emergent serious adverse event related to treatment, two (2%) patients reported an adverse event of special interest, and two (2%) reported a new-onset chronic disease. INTERPRETATION: In patients in the ICU receiving mechanical ventilation with qPCR-confirmed S aureus colonisation of the lower respiratory tract, the incidence of S aureus pneumonia at 30 days was not significantly lower following treatment with 5000 mg suvratoxumab than with placebo. Despite these negative results, monoclonal antibodies still represent one promising therapeutic option to reduce antibiotic consumption that require further exploration and studies. FUNDING: AstraZeneca, with support from the Innovative Medicines Initiative Joint Undertaking.

The Influence of Teachers on Motivation and Academic Stress and Their Effect on the Learning Strategies of University Students.

Students often experience the university period as a very stressful time. The teacher is a key figure who can cushion this stressful experience for the student. This study therefore aims to analyse the influence of teachers from the Self-Determination Theory perspective on academic stress, motivation, critical thinking, metacognitive strategies and academic performance in university students. The study involved 2456 university students with an average age of 22.51 years. A structural equation model was created to analyse the causal relationships between the variables. The results showed that the psychological controlling of the teacher positively predicted academic stress while autonomy support negatively predicted academic stress. Academic stress negatively predicted motivation, metacognitive strategies, critical thinking and academic performance. Academic motivation positively predicted metacognitive strategies and critical thinking. Finally, metacognitive strategies and critical thinking positively predicted academic performance. These results highlight the importance of the role that the teacher adopts during classes and the protective factor of academic motivation in the presence of stress.

The Influence of Transformational Teacher Leadership on Academic Motivation and Resilience, Burnout and Academic Performance.

Currently, the university failure rate is around 33% of students starting their studies. Among the main reasons are demanding academic situations and the use of inappropriate coping strategies. Therefore, the aim of this study was to analyze the influence of teacher leadership on academic resilience and motivation, burnout, and academic performance. This study involved 3354 university students. A structural equation model was made to analyze the predictive relationships between the study's variables. The results showed that teacher leadership positively predicted academic resilience and motivation; academic resilience negatively predicted burnout and positively predicted academic performance; likewise, academic motivation negatively predicted burnout and positively predicted academic performance; finally, burnout negatively predicted academic resilience.