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The global distribution of carbapenemases such as KPC, OXA-48, and metallo-β-lactamases (MBLs) gives cause for concern, as these enzymes are not inhibited by classical β-lactamase inhibitors (BLIs). The current development of new inhibitors is one of the most promising highlights for the treatment of multidrug-resistant bacteria. The activity of cefepime in combination with the novel BLIs zidebactam, taniborbactam, and enmetazobactam was studied in a collection of 400 carbapenemase-producing Enterobacterales (CPE). The genomes were fully sequenced and potential mechanisms of resistance to cefepime/BLI combinations were characterized. Cefepime resistance in the whole set of isolates was 79.5% (MIC50/90 64/≥128mg/L). The cefepime/zidebactam and cefepime/taniborbactam combinations showed the highest activity (MIC(50/90) ≤0.5/1 and ≤0.5/2 mg/L, respectively). Cefepime/zidebactam displayed high activity, regardless of the carbapenemase or extended-spectrum β-lactamase (ESBL) considered (99% of isolates displayed MIC ≤2 mg/L). Cefepime/taniborbactam displayed excellent activity against OXA-48- and KPC-producing Enterobacterales and lower activity against MBL-producing isolates (four strains yielded MICs ≥16 mg/L: 2 NDM producers with an insertion in PBP3, one VIM-1 producer with nonfunctional OmpK35, and one IMP-8 producer). Cefepime/enmetazobactam displayed the lowest activity (MIC(50/90) 1/≥128 mg/L), with MICs ≥16 mg/L for 49 MBL producers, 40 OXA-48 producers (13 with amino acid changes in OmpK35/36, 4 in PBPs and 11 in RamR) and 25 KPC producers (most with an insertion in OmpK36). These results confirm the therapeutic potential of the new β-lactamase inhibitors, shedding light on the activity of cefepime and BLIs against CPE and resistance mechanisms. The cefepime/zidebactam and cefepime/taniborbactam combinations are particularly highlighted as promising alternatives to penicillin-based inhibitors for the treatment of CPE.

Carbapenem resistance is increasing among Gram-negative bacteria, including the genus Acinetobacter. This study aimed to characterize, for the first time, the development of carbapenem resistance in clinical isolates of Acinetobacter junii and Acinetobacter nosocomialis conferred by the acquisition of a plasmid-borne

A challenge preventing successful inverse kinematics measurements with heavy nuclei that are not fully stripped is identifying and tagging the beam particles. For this purpose, the HEavy ISotope Tagger (HEIST) has been developed. HEIST utilizes two micro-channel plate timing detectors to measure time of flight, a multi-sampling ion chamber to measure energy loss, and a high purity Ge detector to identify isomer decays and calibrate the isotope identification system. HEIST has successfully identified $^{198}$Pb and other nearby nuclei at energies of about 75 MeV/A. In the experiment discussed, a typical cut containing 89\% of all $^{198}$Pb$^{+80}$ in the beam had a purity of 86\%. We examine the issues of charge state contamination. The observed charge state populations of these ions are presented and are moderately well described by the charge state model GLOBAL., Comment: The following article has been submitted to Review of Scientific Instruments

[Abstract] Carbapenem resistance is increasing among Gram-negative bacteria, including the genus Acinetobacter. This study aimed to characterize, for the first time, the development of carbapenem resistance in clinical isolates of Acinetobacter junii and Acinetobacter nosocomialis conferred by the acquisition of a plasmid-borne blaOXA-24/40 gene and also to characterize the dissemination of this gene between species of Acinetobacter. Carbapenem-resistant A. nosocomialis HUAV-AN66 and A. junii HUAV-AJ77 strains were isolated in the Arnau de Vilanova Hospital (Spain). The genomes were sequenced, and in silico analysis were performed to characterize the genetic environment and the OXA-24/40 transmission mechanism. Antibiotic MICs were determined, and horizontal transfer assays were conducted to evaluate interspecies transmission of OXA-24/40. Carbapenems MICs obtained were ≥64 mg/L for HUAV-AN66 and HUAV-AJ77. Genome analysis revealed the presence in both strains of a new plasmid, designated pHUAV/OXA-24/40, harboring the carbapenem-resistance gene blaOXA-24/40 and flanked by sequences XerC/XerD. pHUAV/OXA-24/40 was successfully transferred from A. nosocomialis and A. junii to a carbapenem-susceptible A. baumannii strain, thus conferring carbapenem resistance. A second plasmid (pHUAV/AMG-R) was identified in both clinical isolates for the successful horizontal transfer of pHUAV/OXA-24/40. blaOXA-24/40-carrying plasmids of the GR12 group and showing high identity with pHUAV/OXA-24/40 were identified in at least 8 Acinetobacter species. In conclusion the carbapenemase OXA-24/40 is described for the first time in A. nosocomialis and A. junii. In both isolates the blaOXA-24/40 gene was located in the GR12 pHUAV/OXA-24/40 plasmid. GR12 plasmids are implicated in the dissemination and spread of carbapenem resistance among Acinetobacter species. IMPORTANCE Acinetobacter baumannii is one of the most relevant pathogens in terms of antibiotic resistance. The main resistance mechanisms are the carbapenem-hydrolyzing class D β-lactamases (CHDLs), especially OXA-23 and OXA-24/40. In addition to A. baumannii, there are other species within the genus Acinetobacter, which in general exhibit much lower resistance rates. In this work we characterize for the first time two clinical isolates of Acinetobacter nosocomialis and Acinetobacter junii, isolated in the same hospital, carrying the carbapenemase OXA-24/40 and displaying high resistance rates to carbapenems. By means of bioinformatics analysis we have also been able to characterize the mechanism by which this carbapenemase is horizontally transferred interspecies of Acinetobacter spp. The dissemination of carbapenemase OXA-24/40 between non-baumannii Acinetobacter species is concerning since it prevents the use of most β-lactam antibiotics in the fight against these resistant isolates. This work was supported by Projects PI17/01482 and PI20/01212 awarded to A.B. and PI18/00501 to G.B., all within in the National Plan for Scientific Research, Development and Technological Innovation 2013–2016 and funded by the ISCIII - General Subdirection of Assessment and Promotion of the Research-European Regional Development Fund (FEDER) “A way of making Europe.” The work was also supported by CIBERINF (CIBER de Enfermedades Infecciosas). The study was also funded by project IN607A 2020/05 (GAIN- Agencia Gallega de Innovación - Consellería de Economía, Emprego e Industria) awarded to G.B. and IN607D 2021/12 awarded to A.B. This work was also supported by Planes Nacionales de I+D+i2008 to 2011/2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía y Competitividad, Spanish Network for Research in Infectiosus Diseases (REIPI RD16/0016/006) cofinanced by European Development Regional Fund “A way to achieve Europe” and operative program Intelligent Growth 2014–2020. J.A.-S.was financially supported by the Rio Hortega program (ISCIII, CM19/00219), J.C.V.-U. was financially supported by the pFIS program (ISCIII, PI17/01482), C.L.-M. was financially supported by IN606A-2019/029 Grant (Xunta de Galicia) and P.G.-S. was financially supported by IN607A 2020/05 Grant (Xunta de Galicia) Xunta de Galicia; IN607A 2020/05 Xunta de Galicia; IN607D 2021/12 Xunta de Galicia; IN606A-2019/029

Traballo fin de grao (UDC.DER). Dereito. Curso 2021/2022

Traballo Fin de Grao en Pedagoxía. Curso 2021-2022 O presente traballo responde a unha iniciación á investigación de campo co obxectivo de coñecer as relacións existentes entre a comunidade educativa e o conxunto da cidadanía do concello de San Sadurniño para determinar o grao de desenvolvemento da participación social no municipio. Tralo encadre teórico das relacións entre familia, escola e comunidade e as vías da participación social, séguese unha metodoloxía que combina métodos cuantitativos e cualitativos para recoller as perspectivas do Centro educativo, a Administración local e o tecido asociativo veciñal do concello de San Sadurniño. A análise da información recollida das tres partes ofrece unha visión xeral da realidade do municipio onde o CPI San Sadurniño e o Concello manteñen unha relación forte e fluída, postulándose como o eixe condutor para as accións comunitarias ante a baixa implicación familiar e a debilidade das relacións entre o tecido asociativo veciñal. Os resultados obtidos pretenden servir como punto de partida para posibles accións futuras que busquen a integración de todos os axentes sociais El presente trabajo responde a una iniciación a la investigación de campos con el objetivo de conocer las relaciones existentes entre la comunidad educativa y el conjunto de la ciudadanía del municipio de San Sadurniño para determinar el grado de desarrollo de la participación social en el mismo. Tras el encuadre teórico de las relaciones entre familia, escuela y comunidad y las vías de participación social, se decide una metodología que combina métodos cuantitativos y cualitativos para recoger las perspectivas del Centro educativo, la Administración local y el tejido asociativo vecinal del municipio de San Sadurniño. En análisis de la información recogida de las tres partes ofrece una visión general de la realidad del municipio donde el CPI San Sadurniño y el Ayuntamiento mantienen una relación fuerte y fluida, postulándose como el eje conductor para las acciones comunitarias ante la baja implicación familiar y la debilidad de las relaciones entre el tejido asociativo vecinal. Los resultados obtenidos pretenden servir como punto de partida para posibles acciones futuras que busquen la integración de todos los agentes sociales The following paper responds to an initiation to the field investigation with the objective of knowing the existing relationships between the learning community and the citizens of San Sadurniño’s township in order to determine its degree of development in social participation. After the theoretical framing of the relationships between school, family and community, and the social participation tracks, a methodology that combines quantitative and qualitative methods is chosen for the collection of the perspectives of the educational center and the neighborhood’s association networks of the township of San Sadurniño. The analysis of the recovered information of the three parts offers a general vision of the reality of the township, where the CPI San Sadurniño and the city hall maintain a strong and fluid relationship, applying as a conductor axle for communitarian actions in view of the low family involvement and the weakness of the neighborhood’s association networks. The obtained results will serve as a starting point for possible future actions that look forward to the integration of all the social agents

13 pags., 8 figs., 1 tab., We measured 135 cross sections of residual nuclei produced in fragmentation reactions of C12, N14, and O13−16,20,22 projectiles impinging on a carbon target at kinetic energies of near 400A MeV, most of them for the first time, with the RB3/LAND setup at the GSI facility in Darmstadt (Germany). The use of this state-of-the-art experimental setup in combination with the inverse kinematics technique gave the full identification in atomic and mass numbers of fragmentation residues with a high precision. The cross sections of these residues were determined with uncertainties below 20% for most of the cases. These data are compared to other previous measurements with stable isotopes and are also used to benchmark different model calculations., This work has been partially supported by the Spanish Ministry for Science and Innovation under Grants No. PGC2018-099746-B-C21, No. PGC2018-099746-B-C22, and No. PID2019-104390GB-100; Xunta de Galicia under program “Grupos de referencia competitiva” (Project No. ED431C 2017/54); the German Bundesministerium für Bildung und Forschung (BMBF) (Grants No. 05P12RDFN8, No. 05P15RDFN1, and No. 05P19RDFN); the Swedish Research Council; and U.S. Department of Energy Grant No. DE-FG02-08ER41533. J.J.R.S. acknowledges the support of Xunta de Galicia under Grant No. ED481B-2017/002.

Apresentação do Dossier Temático da revista Medievalista intitulado “Intercâmbios Peninsulares”. O dossier temático constitui um dos resultados do projeto "Transferencias humanas, culturales e ideológicas entre los reinos ibéricos (siglos XIII-XV)" (Ref. HAR2017-89398-P), financiado pelo Ministerio de Economía, Industria y Competitividad, de Espanha. Projeto "Transferencias humanas, culturales e ideológicas entre los reinos ibéricos (siglos XIII-XV)" (Ref. HAR2017-89398-P), financiado pelo Ministerio de Economía, Industria y Competitividad, de Espanha. info:eu-repo/semantics/publishedVersion

Urban drainage systems face intrinsic constraints related to the deterioration of infrastructure, the interaction between systems, and increasing requirements and stresses that lower the quality of provided services. Furthermore, climate change and the need for the efficient use of resources are providing additional pressures that cannot be addressed solely with “Business-as-usual” solutions. In this paper, the consequences of such problems and limitations on the urban environment have been assessed through the identification of linked major impacts (e.g., urban flooding and pollution events) and societal externalities (e.g., economic losses, health and social issues, and environmental risks). Since Nature-based Solutions (NBS) consider human well-being, socio-economic development, and governance principles, they open new perspectives regarding urban sustainability, quality of life, and climate change adaptation. To highlight their added value to existing Urban Drainage Systems (UDS), the synergies that result from implementing NBS with traditional urban drainage systems were identified and assessed. Based on a comprehensive framework, for both wastewater and stormwater, the relevant opportunities for rethinking UDS and NBS were identified. Most relevant positive effects go beyond the mitigation of existing intrinsic constraints of traditional systems (e.g., dealing with the control of pollutants or stormwater management) since NBS also provide important economic, social, and environmental co-benefits by including water in urban planning and providing greener open spaces. This integrated and complementary solution not only represents a contribution to the sustainable management of urban water, but also enables an increase in the resilience of urban areas and, in particular, water services against climate change and for additional social co-benefits.

In Solid-State Chemistry, a well-known route to obtain new compounds and modulate their properties is the formation of solid solutions, a strategy widely exploited in the case of classical inorganic perovskites but relatively unexplored among emergent hybrid organic–inorganic perovskites (HOIPs). In this work, to the best of our knowledge, we present the first dicyanamide-perovskite solid solution of [TPrA][Co0.5Ni0.5(dca)3] and study its thermal, dielectric and optical properties, comparing them with those of the parent undoped compounds [TPrA][Co(dca)3] and [TPrA][Ni(dca)3]. In addition, we show that the prepared doped compound can be used as a precursor that, by calcination, allows CNTs with embedded magnetic Ni:Co alloy nanoparticles to be obtained through a fast and much simpler synthetic route than other complex CVD or arc-discharge methods used to obtain this type of material.

Infections caused by ceftolozane-tazobactam and ceftazidime-avibactam-resistant P. aeruginosa infections are an emerging concern. We aimed to analyze the underlying ceftolozane-tazobactam and ceftazidime-avibactam resistance mechanisms in all multidrug-resistant or extensively drug-resistant (MDR/XDR) P. aeruginosa isolates recovered during 1 year (2020) from patients with a documented P. aeruginosa infection. Fifteen isolates showing ceftolozane-tazobactam and ceftazidime-avibactam resistance were evaluated. Clinical conditions, previous positive cultures, and β-lactams received in the previous month were reviewed for each patient. MICs were determined by broth microdilution. Multilocus sequence types (MLSTs) and resistance mechanisms were determined using short- and long-read whole-genome sequencing (WGS). The impact of Pseudomonas-derived cephalosporinases (PDCs) on β-lactam resistance was demonstrated by cloning into an ampC-deficient PAO1 derivative (PAOΔC) and construction of 3D models. Genetic support of acquired β-lactamases was determined in silico from high-quality hybrid assemblies. In most cases, the isolates were recovered after treatment with ceftolozane-tazobactam or ceftazidime-avibactam. Seven isolates from different sequence types (STs) owed their β-lactam resistance to chromosomal mutations and all displayed specific substitutions in PDC: Phe121Leu and Gly222Ser, Pro154Leu, Ala201Thr, Gly214Arg, ΔGly203-Glu219, and Glu219Lys. In the other eight isolates, the ST175 clone was overrepresented (6 isolates) and associated with IMP-28 and IMP-13, whereas two ST1284 isolates produced VIM-2. The cloned PDCs conferred enhanced cephalosporin resistance. The 3D PDC models revealed rearrangements affecting residues involved in cephalosporin hydrolysis. Carbapenemases were chromosomal (VIM-2) or plasmid-borne (IMP-28, IMP-13) and associated with class-1 integrons located in Tn402-like transposition modules. Our findings highlighted that cephalosporin/β-lactamase inhibitors are potential selectors of MDR/XDR P. aeruginosa strains producing PDC variants or metallo-β-lactamases. Judicious use of these agents is encouraged.

Perinatal transmission of HIV has dramatically decreased in high-income countries in the last few years with current rates below 1%, but it still occurs in high-risk situations, mainly pregnant women with late diagnosis of infection, poor antiretroviral adherence and a high viral load (VL). In these high-risk situations, many providers recommend combined neonatal prophylaxis (CNP). Our aim was to evaluate the safety and toxicity of CNP in infants deemed at high-risk of HIV infection among mother-infant pairs in the Madrid Cohort.Prospective, multicenter, observational cohort study between years 2000 and 2019. The subgroup of newborns on CNP and their mothers were retrospectively selected (cohort A) and compared with those who received monotherapy with zidovudine (cohort B). Infants with monotherapy were classified according to treatment regimes in long (6 weeks) and short (4 weeks) course.We identified 227 newborns (33.3% preterm and 7 sets of twins) with CNP. A maternal diagnosis of HIV-1 infection was established during the current pregnancy in 72 cases (36.4%) and intrapartum or postpartum in 31 cases (15.7%). Most infants received triple combination antiretroviral therapy (65.6%; n = 149). The perinatal transmission rate in cohort A was 3.5% (95% confidence interval: 1.13%-5.92%). Infants from cohort A developed anemia (26.1% vs. 19.4%, P = 0.14) and neutropenia more frequently at 50-120 days (21.4% vs. 10.9%, P0.01), without significant differences in grade 3 and 4 anemia or neutropenia between the two cohorts. There were no differences in increased alanine aminotransferase. Neutropenia was more common in the long zidovudine regimes.Our findings provide further evidence of the safety of CNP in infants with high-risk of HIV-1 perinatal transmission.

BackgroundLow-dose dexamethasone demonstrated clinical improvement in patients with coronavirus disease 2019 (COVID-19) needing oxygen therapy; however, evidence on the efficacy of high-dose dexamethasone is limited.MethodsWe performed a randomised, open-label, controlled trial involving hospitalised patients with confirmed COVID-19 pneumonia needing oxygen therapy. Patients were randomly assigned in a 1:1 ratio to receive low-dose dexamethasone (6 mg once daily for 10 days) or high-dose dexamethasone (20 mg once daily for 5 days, followed by 10 mg once daily for an additional 5 days). The primary outcome was clinical worsening within 11 days since randomisation. Secondary outcomes included 28-day mortality, time to recovery and clinical status at day 5, 11, 14 and 28 on an ordinal scale ranging from 1 (discharged) to 7 (death).ResultsA total of 200 patients (mean±sd age 64±14 years; 62% male) were enrolled. 32 (31.4%) out of 102 patients enrolled in the low-dose group and 16 (16.3%) out of 98 in the high-dose group showed clinical worsening within 11 days since randomisation (rate ratio 0.427, 95% CI 0.216–0.842; p=0.014). The 28-day mortality was 5.9% in the low-dose group and 6.1% in the high-dose group (p=0.844). There was no significant difference in time to recovery, and in the seven-point ordinal scale at days 5, 11, 14 and 28.ConclusionsAmong hospitalised COVID-19 patients needing oxygen therapy, high dose of dexamethasone reduced clinical worsening within 11 days after randomisation, compared with low dose.

Staphylococcus aureus is regarded as a threatening bacterial pathogen causing invasive pneumonia in healthcare settings and in the community. The continuous emergence of multidrug resistant strains is narrowing the treatment options for these infections. The development of an effective S. aureus vaccine is, therefore, a global priority. We have previously developed a vaccine candidate, 132 ΔmurI Δdat, which is auxotrophic for D-glutamate, and protects against sepsis caused by S. aureus. In the present study, we explored the potential of this vaccine candidate to prevent staphylococcal pneumonia, by using an acute lung infection model in BALB/c mice. Intranasal inoculation of the vaccine strain yielded transitory colonization of the lung tissue, stimulated production of relevant serum IgG and secretory IgA antibodies in the lung and distal vaginal mucosa and conferred cross-protection to acute pneumonia caused by clinically important S. aureus strains. Although these findings are promising, additional research is needed to minimize dose-dependent toxicity for safer intranasal immunization with this vaccine candidate.