Protective Yeasts Control V. anguillarum Pathogenicity and Modulate the Innate Immune Response of Challenged Zebrafish (Danio rerio) Larvae

Indexación: Web of ScienceWe investigated mechanisms involved in the protection of zebrafish (Danio rerio) larvae by two probiotic candidate yeasts, Debaryornyces hansenii 97 (Dh97) and Yarrowia Iypolitica 242 (YI242), against a Vibrio anguillarum challenge. We determined the effect of different yeast concentrations (10(4)-10(7) CFU/mL) to: (i) protect larvae from the challenge, (ii) reduce the in vivo pathogen concentration and (iii) modulate the innate immune response of the host. To evaluate the role of zebrafish microbiota in protection, the experiments were performed in conventionally raised and germ free larvae. In vitro co-aggregation assays were performed to determine a direct yeast-pathogen interaction. Results showed that both yeasts significantly increased the survival rate of conventionally raised larvae challenged with V. anguillarum. The concentration of yeasts in larvae tended to increase with yeast inoculum, which was more pronounced for Dh97. Better protection was observed with Dh97 at a concentration of 106 CFU/mL compared to 104 CFU/mL. In germ-free conditions V anguillarum reached higher concentrations in larvae and provoked significantly more mortality than in conventional conditions, revealing the protective role of the host microbiota. Interestingly, yeasts were equally (Dh97) or more effective (YI242) in protecting germ-free than conventionally-raised larvae, showing that protection can be exerted only by yeasts and is not necessarily related to modulation of the host microbiota. Although none of the yeasts co aggregated with V anguillarum, they were able to reduce its proliferation in conventionally raised larvae, reduce initial pathogen concentration in germ-free larvae and prevent the upregulation of key components of the inflammatory/anti-inflammatory response (il1b, tnfa, c3, mpx, and il10, respectively). These results show that protection by yeasts of zebrafish larvae challenged with V anguillarum relates to an in vivo anti-pathogen effect, the modulation of the innate immune system, and suggests that yeasts avoid the host-pathogen interaction through mechanisms independent of co-aggregation. This study shows, for the first time, the protective role of zebrafish microbiota against V. anguillarum infection, and reveals mechanisms involved in protection by two non-Saccharomyces yeasts against this pathogen.http://journal.frontiersin.org/article/10.3389/fcimb.2016.00127/ful

Evaluating the capacity of human gut microorganisms to colonize the zebrafish larvae (Danio rerio)

Indexación: Scopus.In this study we evaluated if zebrafish larvae can be colonized by human gut microorganisms. We tested two strategies: (1) through transplantation of a human fecal microbiota and (2) by successively transplanting aerotolerant anaerobic microorganisms, similar to the colonization in the human intestine during early life. We used conventionally raised zebrafish larvae harboring their own aerobic microbiota to improve the colonization of anaerobic microorganisms. The results showed with the fecal transplant, that some members of the human gut microbiota were transferred to larvae. Bacillus, Roseburia, Prevotella, Oscillospira, one unclassified genus of the family Ruminococcaceae and Enterobacteriaceae were detected in 3 days post fertilization (dpf) larvae; however only Bacillus persisted to 7 dpf. Successive inoculation of Lactobacillus, Bifidobacterium and Clostridioides did not improve their colonization, compared to individual inoculation of each bacterial species. Interestingly, the sporulating bacteria Bacillus clausii and Clostridioides difficile were the most persistent microorganisms. Their endospores persisted at least 5 days after inoculating 3 dpf larvae. However, when 5 dpf larvae were inoculated, the proportion of vegetative cells in larvae increased, revealing proliferation of the inoculated bacteria and better colonization of the host. In conclusion, these results suggest that it is feasible to colonize zebrafish larvae with some human bacteria, such as C. difficile and Bacillus and open an interesting area to study interactions between these microorganisms and the host. © 2018 Valenzuela, Caruffo, Herrera, Medina, Coronado, Feijóo, Muñoz, Garrido, Troncoso, Figueroa, Toro, Reyes-Jara, Magne and Navarrete.https://www.frontiersin.org/articles/10.3389/fmicb.2018.01032/ful

Impact of manufacturing tolerances on axial flux permanent magnet machines with ironless rotor core: a statistical approach

Axial Flux Permanent Magnet (AFPM) machines with ironless rotors are an attractive and recently studied solution in low-speed applications, due to their potentially high power/weight ratio, high aspect ratio, and high efficiency. Nevertheless, these machines are prone to be affected by manufacturing tolerance during its fabrication process and consequently, the magnets may move freely inside the rotor structure. This work presents a statistical analysis of manufacturing tolerances of an AFPM machine with an ironless rotor, considering several magnet fault types. A computationally efficient superposition method is developed and implemented to obtain both the cogging torque and rated torque considering several tolerance combinations with acceptable accuracy. The results obtained from a statistical analysis of 10,000 designs of a two-stator one rotor tooth coil winding AFPM (TCW-AFPM) machine allowed us to identify the parameters with the most impact on relevant performance indicators and disclosed a substantial increase in cogging and ripple torque when unavoidable combined tolerances are present

Association of common ATM variants with familial breast cancer in a South American population

Background: The ATM gene has been frequently involved in hereditary breast cancer as a low-penetrance susceptibility gene but evidence regarding the role of ATM as a breast cancer susceptibility gene has been contradictory. Methods: In this study, a full mutation analysis of the ATM gene was carried out in patients from 137 Chilean breast cancer families, of which 126 were BRCA1/2 negatives and 11 BRCA1/2 positives. We further perform a case-control study between the subgroup of 126 cases BRCA1/2 negatives and 200 controls for the 5557G > A missense variant and the IVS38-8T > C and the IVS24-9delT polymorphisms. Results: In the full mutation analysis we detected two missense variants and eight intronic polymorphisms. Carriers of the variant IVS24-9delT, or IVS38-8T > C, or 5557G > A showed an increase in breast cancer risk. The higher significance was observed in the carriers of IVS38-8T > C (OR = 3.09 [95% CI 1.11-8.59], p = 0.024). The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype confered a 3.19 fold increase in breast cancer risk (OR = 3.19 [ 95% CI 1.16-8.89], p = 0.021). The haplotype estimation suggested a strong linkage disequilibrium between the three markers (D' = 1). We detected only three haplotypes in the cases and control samples, some of these may be founder haplotypes in the Chilean population. Conclusion: The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype alone or in combination with certain genetic background and/or environmental factors, could modify the cancer risk by increasing genetic inestability or by altering the effect of the normal DNA damage response

Probiotic Yeasts and Vibrio anguillarum Infection Modify the Microbiome of Zebrafish Larvae

The host microbiome plays an essential role in health and disease. Microbiome modification by pathogens or probiotics has been poorly explored especially in the case of probiotic yeasts. Next-generation sequencing currently provides the best tools for their characterization. Debaryomyces hansenii 97 (D. hansenii 97) and Yarrowia lipolytica 242 (Y. lipolytica 242) are yeasts that protect wildtype zebrafish (Danio rerio) larvae against a Vibrio anguillarum (V. anguillarum) infection, increasing their survival rate. We investigate the effect of these microorganisms on the microbiome and neutrophil response (inflammation) in zebrafish larvae line Tg(Bacmpx:GFP)i114. We postulated that preinoculation of larvae with yeasts would attenuate the intestinal neutrophil response and prevent modification of the larval microbiome induced by the pathogen. Microbiome study was performed by sequencing the V3-V4 region of the 16S rRNA gene and prediction of metabolic pathways by Piphillin in conventionally raised larvae. Survival and the neutrophil response were both evaluated in conventional and germ-free conditions. V. anguillarum infection resulted in higher neutrophil number in the intestinal area compared to non-infected larvae in both conditions. In germ-free conditions, infected larvae pre-inoculated with yeasts showed fewer neutrophil numbers than infected larvae. In both conditions, only D. hansenii 97 increased the survival of infected larvae. Beta diversity of the microbiota was modified by V. anguillarum and both yeasts, compared to non-inoculated larvae. At 3 days post-infection, V. anguillarum modified the relative abundance of 10 genera, and pre-inoculation with D. hansenii 97 and Y. lipolytica 242 prevented the modification of 5 and 6 of these genera, respectively. Both yeasts prevent the increase of Ensifer and Vogesella identified as negative predictors for larval survival (accounting for 40 and 27 of the variance, respectively). In addition, yeast pre-inoculation prevents changes in some metabolic pathways altered by V. anguillarum’s infection. These results suggest that both yeasts and V. anguillarum can shape the larval microbiota configuration in the early developmental stage of D. rerio. Moreover, modulation of key taxa or metabolic pathways of the larval microbiome by yeasts can be associated with the survival of infected larvae. This study contributes to the understanding of yeast–pathogen–microbiome interactions, although further studies are needed to elucidate the mechanisms involved

Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

publishersversionPeer reviewe

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: a systematic review and modelling study

Background: Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middle-income countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018. Methods: We estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and population-based childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries. Findings: In 2018, among children under 5 years globally, there were an estimated 109·5 million influenza virus episodes (uncertainty range [UR] 63·1–190·6), 10·1 million influenza-virus-associated ALRI cases (6·8–15·1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000–1 415 000), 15 300 in-hospital deaths (5800–43 800), and up to 34 800 (13 200–97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries. Interpretation: A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middle-income countries. Funding: WHO; Bill & Melinda Gates Foundation.Fil: Wang, Xin. University of Edinburgh; Reino UnidoFil: Li, You. University of Edinburgh; Reino UnidoFil: O'Brien, Katherine L.. University Johns Hopkins; Estados UnidosFil: Madhi, Shabir A.. University of the Witwatersrand; SudáfricaFil: Widdowson, Marc Alain. Centers for Disease Control and Prevention; Estados UnidosFil: Byass, Peter. Umea University; SueciaFil: Omer, Saad B.. Yale School Of Public Health; Estados UnidosFil: Abbas, Qalab. Aga Khan University; PakistánFil: Ali, Asad. Aga Khan University; PakistánFil: Amu, Alberta. Dodowa Health Research Centre; GhanaFil: Azziz-Baumgartner, Eduardo. Centers for Disease Control and Prevention; Estados UnidosFil: Bassat, Quique. University Of Barcelona; EspañaFil: Abdullah Brooks, W.. University Johns Hopkins; Estados UnidosFil: Chaves, Sandra S.. Centers for Disease Control and Prevention; Estados UnidosFil: Chung, Alexandria. University of Edinburgh; Reino UnidoFil: Cohen, Cheryl. National Institute For Communicable Diseases; SudáfricaFil: Echavarría, Marcela Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Fasce, Rodrigo A.. Public Health Institute; ChileFil: Gentile, Angela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Gordon, Aubree. University of Michigan; Estados UnidosFil: Groome, Michelle. University of the Witwatersrand; SudáfricaFil: Heikkinen, Terho. University Of Turku; FinlandiaFil: Hirve, Siddhivinayak. Kem Hospital Research Centre; IndiaFil: Jara, Jorge H.. Universidad del Valle de Guatemala; GuatemalaFil: Katz, Mark A.. Clalit Research Institute; IsraelFil: Khuri Bulos, Najwa. University Of Jordan School Of Medicine; JordaniaFil: Krishnan, Anand. All India Institute Of Medical Sciences; IndiaFil: de Leon, Oscar. Universidad del Valle de Guatemala; GuatemalaFil: Lucero, Marilla G.. Research Institute For Tropical Medicine; FilipinasFil: McCracken, John P.. Universidad del Valle de Guatemala; GuatemalaFil: Mira-Iglesias, Ainara. Fundación Para El Fomento de la Investigación Sanitaria; EspañaFil: Moïsi, Jennifer C.. Agence de Médecine Préventive; FranciaFil: Munywoki, Patrick K.. No especifíca;Fil: Ourohiré, Millogo. No especifíca;Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Rahi, Manveer. University of Edinburgh; Reino UnidoFil: Rasmussen, Zeba A.. National Institutes Of Health; Estados UnidosFil: Rath, Barbara A.. Vienna Vaccine Safety Initiative; AlemaniaFil: Saha, Samir K.. Child Health Research Foundation; BangladeshFil: Simões, Eric A.F.. University of Colorado; Estados UnidosFil: Sotomayor, Viviana. Ministerio de Salud de Santiago de Chile; ChileFil: Thamthitiwat, Somsak. Thailand Ministry Of Public Health; TailandiaFil: Treurnicht, Florette K.. University of the Witwatersrand; SudáfricaFil: Wamukoya, Marylene. African Population & Health Research Center; KeniaFil: Lay-Myint, Yoshida. Nagasaki University; JapónFil: Zar, Heather J.. University of Cape Town; SudáfricaFil: Campbell, Harry. University of Edinburgh; Reino UnidoFil: Nair, Harish. University of Edinburgh; Reino Unid

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks