Search

The Abocador de Can Mata (ACM) composite stratigraphic sequence (els Hostalets de Pierola, Vallès-Penedès Basin, NE Iberian Peninsula) has yielded a diverse primate assemblage from the late Aragonian (Middle to Late Miocene). Detailed litho-, bio-, and magnetostratigraphic control has enabled an accurate dating of these fossil remains. Comparable data, however, were lacking for the nearby locality of Can Mata 1 (CM1), which yielded a dryopithecine canine of a female individual. Given the lack of hipparionin equids and giraffids, CM1 has been correlated to the latest Aragonian (Mammal Neogene [MN] zone MN7+8). Here we revise the age of CM1 based on fieldwork and associated paleomagnetic samplings undertaken in 2018-2021. Our results extend the ACM composite sequence upward and indicate that CM1 correlates to the earliest Vallesian (MN9). The updated ACM sequence has a thickness of ∼300 m and comprises 12 magnetozones correlated to subchrons C5Ar.1r to C5n.2n (∼12.6-11.1 Ma; latest MN6 to earliest MN9, late Aragonian to earliest Vallesian). CM1 is correlated to C5r.1r (11.146-11.056 Ma), with an interpolated age of 11.11 Ma, thus postdating the dispersal of hipparionin horses into the Vallès-Penedès Basin-which is correlated to the previous subchron C5r.1n, with an interpolated age of 11.18 Ma, and by definition marks the beginning of the Vallesian. CM1 also minimally postdates the earliest record of giraffids at ACM-representing their earliest well-dated occurrence in the basin-being correlated to C5r.1n with an interpolated age of 11.11 Ma. We conclude that CM1 has an earliest Vallesian (MN9) age of ∼11.1 Ma, intermediate between the Aragonian dryopithecins and the Vallesian hispanopithecins. Ongoing paleontological surveillance at ACM thus offers the prospect to yield additional earliest Vallesian ape remains, which are essential to clarify their taxonomic allocation as well as to confirm whether hispanopithecins evolved locally from dryopithecins rather than immigrating from elsewhere during MN9., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Infections caused by multidrug-resistant Acinetobacter baumannii would benefit from the development of novel treatment approaches. Compounds that interfere with bacterial iron metabolism, such as iron chelators and gallium nitrate, have previously been shown to have antimicrobial activity against A. baumannii . In this study, we characterize the effect of LpxC inhibitors on the antimicrobial activity of previously characterized iron chelators, 2,2'-bipyridyl (BIP) and deferiprone (DFP), and gallium nitrate (Ga(NO 3 ) 3 ) against A. baumannii reference strains and multidrug-resistant clinical isolates. The LpxC inhibitor LpxC-2 was synergistic with BIP for 30% of strains tested (FICI values: 0.38-1.02), whereas inhibition with LpxC-4 was synergistic with BIP for 60% of strains tested (FICI values: 0.09-0.75). In time-kill assays, combinations of BIP with both LpxC inhibitors demonstrated synergistic activity, with a more than 3 log 10 reduction in bacterial counts compared to BIP alone. LpxC-2 was synergistic with Ga(NO 3 ) 3 for 50% of strains tested (FICI values: 0.27-1.0), whereas LpxC-4 was synergistic with Ga(NO 3 ) 3 for all strains tested (FICI values: 0.08-≤0.50). In time-kill assays, combinations of Ga(NO 3 ) 3 with LpxC-2 and LpxC-4 decreased the growth of both strains compared to each compound separately; however, only the combination with LpxC-4 met the defined criteria for synergy. These results identify a novel synergy between two antimicrobial classes against A. baumannii strains.

Iron is essential for multiple bacterial processes and is thus required for host colonization and infection. The antimicrobial activity of multiple iron chelators and gallium-based therapies against different bacterial species has been characterized in preclinical studies. In this review, we provide a synthesis of studies characterizing the antimicrobial activity of the major classes of iron chelators (hydroxamates, aminocarboxylates and hydroxypyridinones) and gallium compounds. Special emphasis is placed on recent in-vitro and in-vivo studies with the novel iron chelator DIBI. Limitations associated with iron chelation and gallium-based therapies are presented, with emphasis on limitations of preclinical models, lack of understanding regarding mechanisms of action, and potential host toxicity. Collectively, these studies demonstrate potential for iron chelators and gallium to be used as antimicrobial agents, particularly in combination with existing antibiotics. Additional studies are needed in order to characterize the activity of these compounds under physiologic conditions and address potential limitations associated with their clinical use as antimicrobial agents.

Education is going through a period of crisis related to the SARS-CoV-2 pandemic that most probably will follow a continuum organized into distinct phases: emergency, recovery, reconstruction, development, and institutionalization. This article analyzes the response of curriculum to an unpredictable, chaotic, and recursive crisis situation. The article also highlights the role of important, but often forgotten, actors in a formal education system-parents-and examines the stresses the pandemic has placed on them. Finally, in the light of the continuum of the educational crisis and the impacts of Covid-19 on certain curricular dimensions, the article concludes with reflections on the need to rethink curricula, even in education systems that considered themselves robust in their institutionalization., (© UNESCO IBE 2021.)

Introduction: The sensitivities of conventional mycobacterial culture in solid or liquid media and acid-fast bacilli (AFB) smear microscopy for Mycobacterium tuberculosis complex (MTBC) detection in extrapulmonary specimens are suboptimal. We evaluated the field performance of the Abbott RealTime MTB assay for the diagnosis of extrapulmonary tuberculosis in a low-prevalence setting., Methods: The total number of extrapulmonary specimens with mycobacterial culture and PCR results was 566: sterile fluids (n=278), non-sterile fluids (n=147), lymph node material (n=69) tissue biopsies (n=63), and abscess aspirates (n=9). A composite standard consisting of mycobacterial culture results, clinical treatment response to anti-TB drugs, when administered, and histopathology, radiological and laboratory findings were used as a reference for sensitivity and specificity calculations., Results: Mycobacterial cultures and PCR were positive in 17 and 28 specimens, respectively. The overall agreement between culture and PCR was moderate (Cohen's kappa coefficient: 0.549; P=0.0001). Taking as a reference our composite standard, the sensitivity of the Abbott PCR assay was 77.7%, the specificity 99.5%, the PPV 95.4%, and the NPV 98.8%. In turn, the sensitivity of the mycobacterial culture was 62.9%, the specificity and PPV 100%, and the NPV 97.9%., Conclusion: The good field performance of the Abbott RealTime MTB assay makes it valuable for the diagnosis of extrapulmonary tuberculosis in a low-prevalence setting. The use of molecular methods along with culture improves the diagnosis of extrapulmonary tuberculosis., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Background: Vaccination is the primary method for preventing influenza respiratory virus infection (RVI). Although the influenza vaccine is able to achieve serological responses in some allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, its clinical benefits are still uncertain., Methods: In this prospective, cross-sectional study, we retrospectively analyzed the effect of inactivated trivalent influenza vaccination on the prevalence of influenza RVI in a consecutive cohort of 136 allo-HSCT adult recipients who developed 161 RVI over 5 flu seasons (from 2013 to 2018). Respiratory viruses in upper- and/or lower-respiratory tract specimens were tested using multiplex polymerase chain reaction panel assays., Results: Overall, we diagnosed 74 episodes (46%) of influenza RVI in 70 allo-HSCT recipients. Influenza RVI occurred in 51% of the non-vaccinated compared to 36% of the vaccinated recipients (P = .036). A multivariate analysis showed that influenza vaccination was associated with a lower prevalence of influenza RVI (odds ratio [OR] 0.39, P = .01). A multivariate risk factor analysis of lower-respiratory tract disease (LRTD) identified 2 conditions associated with the probability of influenza RVI progression: influenza vaccination (OR 0.12, 95% confidence interval [CI] 0.014-1, P = .05) and a high-risk immunodeficiency score (OR 36, 95% CI 2.26-575, P = .011). Influenza vaccination was also associated with a lower likelihood of an influenza-related hospital admission (14% vs 2%, P = .04)., Conclusions: This study shows that influenza vaccination may have a clinical benefit in allo-HSCT recipients with virologically-confirmed RVI, in terms of a lower influenza RVI prevalence, slower LRTD progression, and lower likelihood of hospital admission., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: To date no definitive cut-off value for cytomegalovirus (CMV) DNA load in bronchoalveolar lavage (BAL) fluid specimens has been established to discriminate between CMV pneumonia and pulmonary CMV DNA shedding in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients., Methods: The current retrospective study is aimed at assessing the range of CMV DNA loads quantified in BAL fluid specimens from allo-HSCT patients with pneumonia in which different microorganisms were causally involved., Results: A total of 144 BAL specimens from 123 patients were included. CMV DNA was detected in 56 out of 144 BAL fluid specimens and the median CMV DNA load from patients in whom CMV pneumonia was unlikely or could be tentatively ruled out was 1210 (31-68, 920) IU/ml. The frequency of CMV DNA detection and median CMV DNA loads were comparable, irrespective of the attributable cause of pneumonia. Detection of CMV DNA loads in BAL fluid specimens >500 IU/ml was independently associated with pneumonia-attributable mortality., Conclusions: The current study highlights the difficulty in establishing universal CMV DNA load thresholds in BAL fluid specimens for distinguishing between CMV pneumonia and pulmonary CMV DNA shedding, and suggests that the presence of CMV DNA in BAL fluid specimens beyond a certain level may have a deleterious impact on patient outcome., (Copyright © 2019. Published by Elsevier Ltd.)

Risk factors (RFs) and mortality data of community-acquired respiratory virus (CARVs) lower respiratory tract disease (LRTD) with concurrent pulmonary co-infections in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is scarce. From January 2011 to December 2017, we retrospectively compared the outcome of allo-HSCT recipients diagnosed of CARVs LRTD mono-infection (n = 52, group 1), to those with viral, bacterial, or fungal pulmonary CARVs LRTD co-infections (n = 15, group 2; n = 20, group 3, and n = 11, group 4, respectively), and with those having bacterial pneumonia mono-infection (n = 19, group 5). Overall survival (OS) at day 60 after bronchoalveolar lavage (BAL) was significantly higher in group 1, 2, and 4 compared to group 3 (77%, 67%, and 73% vs 35%, respectively, P = .012). Recipients of group 5 showed a trend to better OS compared to those of group 3 (62% vs 35%, P = .1). Multivariate analyses showed bacterial co-infection as a RF for mortality (hazard ratio[HR] 2.65, 95% C.I. 1.2-6.9, P = .017). We identified other 3 RFs for mortality: lymphocyte count <0.5 × 10 9 /L (HR 2.6, 95% 1.1-6.2, P = .026), the occurrence of and CMV DNAemia requiring antiviral therapy (CMV-DNAemia-RAT) at the time of BAL (HR 2.32, 95% C.I. 1.1-4.9, P = .03), and the need of oxygen support (HR 8.3, 95% C.I. 2.9-35.3, P = .004). CARV LRTD co-infections are frequent and may have a negative effect in the outcome, in particular in the context of bacterial co-infections., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Vancomycin minimum inhibitory concentrations (MICs) at the upper end of the susceptible range for Staphylococcus aureus have been associated with poor clinical outcomes of bloodstream infections. We tested the hypothesis that high vancomycin MICs in S. aureus bacteraemia isolates are associated with increased cell wall thickness and suboptimal bacterial internalisation or lysis by human phagocytes. In total, 95 isolates were evaluated. Original vancomycin MICs were determined by Etest. The susceptibility of S. aureus isolates to killing by phagocytes was assessed in a human whole blood assay. Internalisation of bacterial cells by phagocytes was investigated by flow cytometry. Cell wall thickness was evaluated by transmission electron microscopy. Genotypic analysis of S. aureus isolates was performed using a DNA microarray system. Vancomycin MICs were significantly higher (P=0.006) in isolates that were killed suboptimally (killing index <60%) compared with those killed efficiently (killing index >70%) and tended to correlate inversely (P=0.08) with the killing indices. Isolates in both killing groups were internalised by human neutrophils and monocytes with comparable efficiency. The cell wall was significantly thicker (P=0.03) in isolates in the low killing group. No genotypic differences were found between the isolates in both killing groups. In summary, high vancomycin MICs in S. aureus bacteraemia isolates were associated with increased cell wall thickness and reduced intracellular killing by phagocytes., (Copyright © 2016 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Objective: To investigate the mechanisms of quinolone resistance and the association with other resistance markers among Esherichia coli (E. coli) strains isolated from outpatient with urinary tract infection in north of Algeria., Methods: A total of 30 nalidixic acid-resistant E. coli isolates from outpatient with urinary tract infections from January 2010 to April 2011 in north of Algeria (Bejaia) were studied. Antimicrobial susceptibility was determined by disc diffusion assay, minimal inhibitory concentrations (MIC) of quinolone were determined by microdilution. Mutations in the Quinolone Resistance-Determining Region (QRDR) of gyrA and parC genes and screening for qnr (A, B and S) and bla genes were done by PCR and DNA sequencing., Results: Most of the E. coli isolates (56.66%) were shown to carry mutations in gyrA and parC (gyrA: Ser83Leu + Asp87Asn and parC:Ser80Ile). While, 16.66% had only an alteration in gyrA: Ser83Leu. One isolate produced qnrB-like and two qnrS-like. Four isolates were CTX-M-15 producers associated with TEM-1 producing in one case. Co-expression of blaCTX-M-15 and qnrB was determined in one E. coli isolate., Conclusions: Our findings suggested the community emergence of gyrA and parC alterations and Qnr determinants that contributed to the development and spread of fluoroquinolone resistance in Algerian E. coli isolates., (Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.)