Serological Survey of Antibodies to Mannheimia haemolytica and Pasteurella multocida in Camelids from Argentina

South American camelids are a source of livestock wealth in Andean countries. In Argentina,there is little information about camelid pathogens, and most of the literature data available areseroprevalence works against virus. Besides, little is known about the immunological status againstbacterial agents affecting these animals. In an effort to explore the serological status of Argentineancamelids, we evaluated the presence of serum antibodies against bacterial pathogens involved inpneumonic diseases (Pasteurella multocida and Mannheimia haemolytica) in llamas from differentregions of the country. By ELISA, a high seroprevalence for both pathogens was found in the serumsamples; higher optical density (OD) values were obtained when the sera were incubated with heatkilledP. multocida as coating antigen compared to M. haemolytica. In addition, a large number ofsera analyzed presented high OD values for both microorganisms independently of their originregion. Serum avidity was also evaluated, by means of an assay based on antibody desorption byurea. No correlation was found between the high ODs obtained for P. multocida and the serumavidity. On the other hand, samples reacting with M. haemolytica had lower OD values but higheravidity index. The antigenic recognition pattern for both microorganisms was determined bywestern blot. Unlike P. multocida, the antigenic recognition pattern of M. haemolytica did not differamong serum samples obtained from animals living in different areas. In summary, we found thatcamelids can synthetize antibodies that recognize M. haemolytica with high avidity for differentantigens of the bacterium, suggesting that Argentinean camelids are in contact with M. haemolyticawhich is probably a causative agent of subclinical infections. Conversely, specific antibodies forP. multocida were also found, but these sera presented low avidity that is probably the result of acolonization process by this bacterium, or else, to be a consequence of cross-reactivity phenomenaFil: Díaz, Ailén Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Ledesma, Martin Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Calcagno, M. L.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Físico Matemática. Cátedra de Matemáticas; ArgentinaFil: Leoni, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Manghi, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Canellada, Andrea Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Castro, Marisa Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentin

Peptidome profiling for the immunological stratification in sepsis: a proof of concept study

Sepsis has been called the graveyard of pharmaceutical companies due to the numerous failed clinical trials. The lack of tools to monitor the immunological status in sepsis constrains the development of therapies. Here, we evaluated a test based on whole plasma peptidome acquired by MALDI-TOF-mass spectrometer and machine-learning algorithms to discriminate two lipopolysaccharide-(LPS) induced murine models emulating the pro- and anti-inflammatory/immunosuppression environments that can be found during sepsis. The LPS group was inoculated with a single high dose of LPS and the IS group was subjected to increasing doses of LPS, to induce proinflammatory and anti-inflammatory/immunosuppression profiles respectively. The LPS group showed leukopenia and higher levels of cytokines and tissue damage markers, and the IS group showed neutrophilia, lymphopenia and decreased humoral response. Principal component analysis of the plasma peptidomes formed discrete clusters that mostly coincided with the experimental groups. In addition, machine-learning algorithms discriminated the different experimental groups with a sensitivity of 95.7% and specificity of 90.9%. Data reveal the potential of plasma fingerprints analysis by MALDI-TOF-mass spectrometry as a simple, speedy and readily transferrable method for sepsis patient stratification that would contribute to therapeutic decision-making based on their immunological status.Fil: Ledesma, Martin Manuel. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Todero, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Maceira, Lautaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Prieto, Monica. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; ArgentinaFil: Vay, Carlos. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Galas, Marcelo Fabián. Organización Panamericana de la Salud; Estados UnidosFil: López, Beatriz. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; ArgentinaFil: Yokobori, Noemí. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

A combined approach of MALDI-TOF mass spectrometry and multivariate analysis as a potential tool for the detection of SARS-CoV-2 virus in nasopharyngeal swabs

Coronavirus disease 2019, known as COVID-19, is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The early, sensitive and specific detection of SARS-CoV-2 virus is widely recognized as the critical point in responding to the ongoing outbreak. Currently, the diagnosis is based on molecular real time RT-PCR techniques, although their implementation is being threatened due to the extraordinary demand for supplies worldwide. That is why the development of alternative and / or complementary tests becomes so relevant. Here, we exploit the potential of mass spectrometry technology combined with machine learning algorithms, for the detection of COVID-19 positive and negative protein profiles directly from nasopharyngeal swabs samples. According to the preliminary results obtained, accuracy =67.66 %, sensitivity =61.76 %, specificity =71.72 %, and although these parameters still need to be improved to be used as a screening technique, mass spectrometry- based methods coupled with multivariate analysis showed that it is an interesting tool that deserves to be explored as a complementary diagnostic approach due to the low cost and fast performance. However, further steps, such as the analysis of a large number of samples, should be taken in consideration to determine the applicability of the method developed.Fil: Rocca, María Florencia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina. Universidad Nacional de Santiago del Estero. Facultad de Humanidades Ciencias Sociales y de la Salud. Instituto de Estudios e Investigaciones en Enfermería; Argentina. Red Nacional de Espectrometría de Masas Aplicada a la Microbiología Clínica; ArgentinaFil: Zintgraff, Jonathan Cristian. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina. Universidad Nacional de Santiago del Estero. Facultad de Humanidades Ciencias Sociales y de la Salud. Instituto de Estudios e Investigaciones en Enfermería; Argentina. Red Nacional de Espectrometría de Masas Aplicada a la Microbiología Clínica; ArgentinaFil: Dattero, María Elena. Universidad Nacional de Santiago del Estero. Facultad de Humanidades Ciencias Sociales y de la Salud. Instituto de Estudios e Investigaciones en Enfermería; Argentina. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Medicina Tropical; ArgentinaFil: Santos, Leonardo Silva. Universidad de Talca; ChileFil: Ledesma, Martin Manuel. Red Nacional de Espectrometría de Masas Aplicada A la Microbiología Clínica (renaem Argentina); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vay, Carlos Alberto. Red Nacional de Espectrometría de Masas Aplicada a la Microbiología Clínica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Prieto, Mónica Raquel. Red Nacional de Espectrometría de Masas Aplicada a la Microbiología Clínica; Argentina. Universidad de Buenos Aires; ArgentinaFil: Benedetti, Estefanía. Universidad Nacional de Santiago del Estero. Facultad de Humanidades Ciencias Sociales y de la Salud. Instituto de Estudios e Investigaciones en Enfermería; Argentina. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Medicina Tropical; ArgentinaFil: Avaro, Martín. Universidad Nacional de Santiago del Estero. Facultad de Humanidades Ciencias Sociales y de la Salud. Instituto de Estudios e Investigaciones en Enfermería; Argentina. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Medicina Tropical; ArgentinaFil: Russo, Mara Laura. Universidad Nacional de Santiago del Estero. Facultad de Humanidades Ciencias Sociales y de la Salud. Instituto de Estudios e Investigaciones en Enfermería; Argentina. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Medicina Tropical; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nachtigall, Fabiane Manke. Universidad Autónoma de Chile; ChileFil: Baumeister, Elsa. Universidad Nacional de Santiago del Estero. Facultad de Humanidades Ciencias Sociales y de la Salud. Instituto de Estudios e Investigaciones en Enfermería; Argentina. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Medicina Tropical; Argentin

The synthetic phospholipid C8-C1P determines pro-angiogenic and pro-reparative features in human macrophages restraining the proinflammatory M1-like phenotype

Monocytes (Mo) are highly plastic myeloid cells that differentiate into macrophages after extravasation, playing a pivotal role in the resolution of inflammation and regeneration of injured tissues. Wound-infiltrated monocytes/macrophages are more pro-inflammatory at early time points, while showing anti-inflammatory/pro-reparative phenotypes at later phases, with highly dynamic switching depending on the wound environment. Chronic wounds are often arrested in the inflammatory phase with hampered inflammatory/repair phenotype transition. Promoting the tissue repair program switching represents a promising strategy to revert chronic inflammatory wounds, one of the major public health loads. We found that the synthetic lipid C8-C1P primes human CD14+ monocytes, restraining the inflammatory activation markers (HLA-DR, CD44, and CD80) and IL-6 when challenged with LPS, and preventing apoptosis by inducing BCL-2. We also observed increased pseudo-tubule formation of human endothelial-colony-forming cells (ECFCs) when stimulated with the C1P-macrophages secretome. Moreover, C8-C1P-primed monocytes skew differentiation toward pro-resolutive-like macrophages, even in the presence of inflammatory PAMPs and DAMPs by increasing anti-inflammatory and pro-angiogenic gene expression patterns. All these results indicate that C8-C1P could restrain M1 skewing and promote the program of tissue repair and pro-angiogenic macrophage

In vitro and in vivo anti-Trypanosoma cruzi activity of new arylamine Mannich base-type derivatives

Chagas disease is a neglected tropical disease with 6-7 million people infected worldwide and there is no effective treatment. Therefore, there is an urgent need to continue researching in order to discover novel therapeutic alternatives. We present a series of arylaminoketone derivatives as means of identifying new drugs to treat Chagas disease in the acute phase with greater activity, less toxicity and with a larger spectrum of action than that corresponding to the reference drug benznidazole. Indexes of high selectivity found in vitro formed the basis for later in vivo assays in BALB/c mice. Murine model results show that compounds 3, 4, 7 and 10 induced a remarkable decrease in parasitemia levels in acute phase and the parasitemia reactivation following immunosuppression, and curative rates were higher than with benznidazole. These high anti-parasitic activities encourage us to propose these compounds as promising molecules for developing an easy to synthesize anti-Chagas agent

SALMANTICOR study. Rationale and design of a population-based study to identify structural heart disease abnormalities: a spatial and machine learning analysis

[EN]Introduction: This study aims to obtain data on the prevalence and incidence of structural heart disease in a population setting and, to analyse and present those data on the application of spatial and machine learning methods that, although known to geography and statistics, need to become used for healthcare research and for political commitment to obtain resources and support effective public health programme implementation. Methods and analysis: We will perform a cross-sectional survey of randomly selected residents of Salamanca (Spain). 2400 individuals stratified by age and sex and by place of residence (rural and urban) will be studied. The variables to analyse will be obtained from the clinical history, different surveys including social status, Mediterranean diet, functional capacity, ECG, echocardiogram, VASERA and biochemical as well as genetic analysis. Ethics and dissemination: The study has been approved by the ethical committee of the healthcare community. All study participants will sign an informed consent for participation in the study. The results of this study will allow the understanding of the relationship between the different influencing factors and their relative importance weights in the development of structural heart disease

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Background: Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. Methods: The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. Findings: Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. Interpretation: In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. Funding: Novo Nordisk

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article