In Vitro Activity of Cefiderocol Compared to Other Antimicrobials against a Collection of Metallo-Beta-Lactamase-Producing Gram-Negative Bacilli from Southern Spain.

In this study, we aimed to comparatively evaluate the in vitro activity of cefiderocol versus other antimicrobials against a well-characterized collection of metallo-beta-lactamase (MBL)-producing Gram-negative bacilli (MBL-GNB) isolates from hospitals in Andalusia, Spain. We recovered 232 MBL-GNB from Andalusian hospitals, including 160 Enterobacterales and 72 nonfermenting Gram-negative bacilli belonging to 44 different clones (2015 to 2020). Cefiderocol and comparator MICs were determined with commercial methods (UMIC [Bruker] and EUMDROXF [Sensititre; Thermo Fisher], respectively). EUCAST breakpoints were used for all antimicrobials tested, and CLSI also was used for cefiderocol. Control strains used were E. coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. Cefiderocol showed potent in vitro activity against isolates tested, regardless of breakpoint (susceptibility rates, 85.3% for EUCAST versus 96.6% for CLSI, P < 0.001). MIC ranges for Enterobacterales and nonfermenting Gram-negative bacilli (NF-GNB) were ≤0.03 to 1 mg/L and 0.06 to 2 (IMP), 0.06 to 8 mg/L and 0.06 to 16 (VIM), 0.25 to 16 mg/L and 2 to 16 mg/L (NDM), respectively, and 0.25 to 8 mg/L for double MBL-producing Enterobacterales. By species, all cefiderocol-susceptible rates were over 90%, except Klebsiella oxytoca, Enterobacter cloacae, Escherichia coli, and Acinetobacter spp. Significant differences were observed comparing resistant isolates between Enterobacterales and NF-GNB by EUCAST (19.4% versus 4.2%, P < 0.01), but not by CLSI (4.4% versus 1.4%, P = 0.2). Cefiderocol was the most active antimicrobial tested. Cefiderocol showed excellent in vitro activity against MBL-GNB, especially NF-GNB; almost all isolates resistant to comparators were susceptible. IMPORTANCE This article demonstrates the efficacy of cefiderocol against a large collection of well-characterized metallo-beta-lactamase-producing isolates, some of them even producing double carbapenemases. Furthermore, cefiderocol activity is compared to other novel broad-spectrum antimicrobials with activity against carbapenemases.

Activity of fosfomycin and amikacin against fosfomycin-heteroresistant Escherichia coli strains in a hollow-fiber infection model.

Objectives:To evaluate human-like intravenous doses of fosfomycin (8g/Q8h) and amikacin (15mg/kg/Q24h) efficacy in monotherapy and in combination against six fosfomycin-heteroresistant Escherichia coli isolates using a hollow-fiber infection model (HFIM).Materials and methods:Six fosfomycin-heteroresistant E. coli isolates (4 with strong mutator phenotype) and the control strain E. coli ATCC 25922 were used. Mutant frequencies for rifampin (100mg/L), fosfomycin (50 and 200mg/L) and amikacin (32mg/L) were determined. Fosfomycin and amikacin MICs were assessed by agar dilution (AD), gradient strip (GSA) and broth microdilution (BMD) assays. Fosfomycin and amikacin synergies were studied by checkerboard and time-kill assays at different concentrations. Fosfomycin (8g/Q8h) and amikacin (15mg/kg/Q24h) efficacy alone and in combination were assessed using a HFIM.Results:Five isolates were resistant to fosfomycin by AD and BMD, but all susceptible by GSA. All isolates were considered susceptible to amikacin. Antibiotic combinations were synergistic in two isolates and no antagonism was detected. In time-kill assays, all isolates survived under fosfomycin at 64mg/L, although, at 307mg/L, only the normomutators and two hypermutators survived. Four isolates survived under 16mg/L amikacin and none at 45mg/L. No growth was detected under combination conditions. In HFIM, fosfomycin and amikacin monotherapies failed to sterilise bacterial cultures, however, fosfomycin and amikacin combination showed a rapid eradication.Conclusions.There may be a risk of treatment failure of fosfomycin-heteroresistant E. coli isolates using either amikacin or fosfomycin in monotherapy. These results support that the combination amikacin-fosfomycin can rapidly decrease bacterial burden and prevent the emergence of resistant subpopulations against fosfomycin-heteroresistant strains.

Fenotipo de la enfermedad de Parkinson basado en la edad de inicio en pacientes latinoamericanos: un análisis emparejado / Parkinson’s disease phenotype based on age at onset in Latin American patients: a paired-based analysis

Introducción: Diversos estudios han demostrado una mayor gravedad de sintomatología motora y no motora en pacientes con enfermedad de Parkinson (EP) con edad de inicio tardía comparados con los de inicio intermedio. Decidimos probar estos resultados en una población con EP en Latinoamérica. Pacientes y métodos: Reclutamos a 24 pacientes con EP con una edad de inicio > 65 años (inicio tardío), y cada paciente se emparejó con un control con inicio de la enfermedad entre los 48 y los 60 años (inicio intermedio), emparejados por sexo y duración de la enfermedad (±2 años). Se registraron baterías de pruebas clínicas que evaluaron los síntomas motores –escala unificada de la enfermedad de Parkinson modificada por la Sociedad de Trastornos del Movimiento (MDS-UPDRS)–, los no motores (escala de síntomas no motores), los cognitivos (escala de evaluación cognitiva de Montreal) y la calidad de vida (cuestionario de enfermedad de Parkinson 8). Los grupos se compararon con análisis de regresión logística condicional. Resultados: La edad media de inicio fue de 70,53 ± 3,28 y 53,79 ± 4,96 para los grupos de inicio tardío y de inicio intermedio, respectivamente. No se observaron diferencias significativas en la mayoría de las baterías clínicas cuando se compararon los pacientes con EP según la edad de inicio, con peores puntuaciones significativamente en la MDS-UPDRS, parte III, y en su subdominio de temblor en el grupo de inicio intermedio. Conclusiones: Éste es el primer estudio que informa sobre un fenotipo motor más benigno en pacientes con EP de inicio tardío. A pesar de utilizar una edad de corte más baja para definir el inicio tardío, las características vasculares, epidemiológicas, étnicas y de adhesión al tratamiento también deben considerarse como posibles factores explicativos.(AU)

Introduction: Studies have demonstrated a higher motor and non-motor burden in Parkinson’s disease (PD) patients with old age at onset compared to those with middle age at onset. We decided to test these findings in a Latin American PD population. Patients and methods: We recruited 24 PD patients with age at onset > 65 years, and each patient was matched to 1 control patient with disease onset at ages between 48 and 60 years, matched for gender and disease duration (±2 years). Clinical test batteries that assessed motor (MDS-UPDRS), non-motor (NMSS), cognitive (MoCA), and quality of life (PDQ-8) were recorded. Groups were compared with conditional logistic regression analysis. A comparative post-hoc analysis was also conducted, considering only patients with age at onset > 70 years (n = 11) and their matched controls. Results: Mean age at onset was 70.53 ± 3.28 and 53.79 ± 4.96 for the old-age and middle-age group, respectively. No significant differences were observed in most clinical batteries when comparing PD patients based on age at onset, with worse scores in MDS-UPDRS Part III and Tremor subscore in the middle-age onset group. The post-hoc analysis showed similar results, with non-significantly worse scores in the middle-age onset group. Conclusion: This is the first study reporting a more benign motor phenotype in old-age onset PD patients. Despite the lower cut-off value used for old age onset PD, vascular, epidemiological, ethnic and treatment adherence features must be also considered as potential explicative factors, with further multicenter studies in larger populations needed.(AU)

[Parkinson's disease phenotype based on age at onset in Latin American patients: a paired-based analysis]. / Fenotipo de la enfermedad de Parkinson basado en la edad de inicio en pacientes latinoamericanos: un análisis emparejado.

INTRODUCTION: Studies have demonstrated a higher motor and non-motor burden in Parkinson's disease (PD) patients with old age at onset compared to those with middle age at onset. We decided to test these findings in a Latin American PD population. PATIENTS AND METHODS: We recruited 24 PD patients with age at onset > 65 years, and each patient was matched to 1 control patient with disease onset at ages between 48 and 60 years, matched for gender and disease duration (±2 years). Clinical test batteries that assessed motor (MDS-UPDRS), non-motor (NMSS), cognitive (MoCA), and quality of life (PDQ-8) were recorded. Groups were compared with conditional logistic regression analysis. A comparative post-hoc analysis was also conducted, considering only patients with age at onset > 70 years (n = 11) and their matched controls. RESULTS: Mean age at onset was 70.53 ± 3.28 and 53.79 ± 4.96 for the old-age and middle-age group, respectively. No significant differences were observed in most clinical batteries when comparing PD patients based on age at onset, with worse scores in MDS-UPDRS Part III and Tremor subscore in the middle-age onset group. The post-hoc analysis showed similar results, with non-significantly worse scores in the middle-age onset group. CONCLUSION: This is the first study reporting a more benign motor phenotype in old-age onset PD patients. Despite the lower cut-off value used for old age onset PD, vascular, epidemiological, ethnic and treatment adherence features must be also considered as potential explicative factors, with further multicenter studies in larger populations needed.

TITLE: Fenotipo de la enfermedad de Parkinson basado en la edad de inicio en pacientes latinoamericanos: un análisis emparejado.Introducción. Diversos estudios han demostrado una mayor gravedad de sintomatología motora y no motora en pacientes con enfermedad de Parkinson (EP) con edad de inicio tardía comparados con los de inicio intermedio. Decidimos probar estos resultados en una población con EP en Latinoamérica. Pacientes y métodos. Reclutamos a 24 pacientes con EP con una edad de inicio > 65 años (inicio tardío), y cada paciente se emparejó con un control con inicio de la enfermedad entre los 48 y los 60 años (inicio intermedio), emparejados por sexo y duración de la enfermedad (±2 años). Se registraron baterías de pruebas clínicas que evaluaron los síntomas motores ­escala unificada de la enfermedad de Parkinson modificada por la Sociedad de Trastornos del Movimiento (MDS-UPDRS)­, los no motores (escala de síntomas no motores), los cognitivos (escala de evaluación cognitiva de Montreal) y la calidad de vida (cuestionario de enfermedad de Parkinson 8). Los grupos se compararon con análisis de regresión logística condicional. Resultados. La edad media de inicio fue de 70,53 ± 3,28 y 53,79 ± 4,96 para los grupos de inicio tardío y de inicio intermedio, respectivamente. No se observaron diferencias significativas en la mayoría de las baterías clínicas cuando se compararon los pacientes con EP según la edad de inicio, con peores puntuaciones significativamente en la MDS-UPDRS, parte III, y en su subdominio de temblor en el grupo de inicio intermedio. Conclusiones. Éste es el primer estudio que informa sobre un fenotipo motor más benigno en pacientes con EP de inicio tardío. A pesar de utilizar una edad de corte más baja para definir el inicio tardío, las características vasculares, epidemiológicas, étnicas y de adhesión al tratamiento también deben considerarse como posibles factores explicativos.

Interplay among Different Fosfomycin Resistance Mechanisms in Klebsiella pneumoniae.

The objectives of this study were to characterize the role of the uhpT, glpT, and fosA genes in fosfomycin resistance in Klebsiella pneumoniae and evaluate the use of sodium phosphonoformate (PPF) in combination with fosfomycin. Seven clinical isolates of K. pneumoniae and the reference strain (ATCC 700721) were used, and their genomes were sequenced. ΔuhpT, ΔglpT, and ΔfosA mutants were constructed from two isolates and K. pneumoniae ATCC 700721. Fosfomycin susceptibility testing was done by the gradient strip method. Synergy between fosfomycin and PPF was studied by checkerboard assay and analyzed using SynergyFinder. Spontaneous fosfomycin mutant frequencies at 64 and 512 mg/liter, in vitro activity using growth curves with fosfomycin gradient concentrations (0 to 256mg/liter), and time-kill assays at 64 and 307 mg/liter were evaluated with and without PPF (0.623 mM). The MICs of fosfomycin against the clinical isolates ranged from 16 to ≥1,024 mg/liter. The addition of 0.623 mM PPF reduced fosfomycin MIC between 2- and 8-fold. Deletion of fosA led to a 32-fold decrease. Synergistic activities were observed with the combination of fosfomycin and PPF (most synergistic area at 0.623 mM). The lowest fosfomycin-resistant mutant frequencies were found in ΔfosA mutants, with decreases in frequency from 1.69 × 10-1 to 1.60 × 10-5 for 64 mg/liter of fosfomycin. In the final growth monitoring and time-kill assays, fosfomycin showed a bactericidal effect only with the deletion of fosA and not with the addition of PPF. We conclude that fosA gene inactivation leads to a decrease in fosfomycin resistance in K. pneumoniae The pharmacological approach using PPF did not achieve enough activity, and the effect decreased with the presence of fosfomycin-resistant mutations.

Solution processed nanostructured hybrid materials based on PbS quantum dots and reduced graphene oxide with tunable optoelectronic properties.

Nanostructured hybrid materials (NHMs) are promising candidates to improve the performance of several materials in different applications. In the case of optoelectronic technologies, the ability to tune the optical absorption of such NHMs is an appealing feature. Along with the capacity to transform the absorbed light into charge carriers (CC), and their consequently efficient transport to the different electrodes. In this regard, NHM based on graphene-like structures and semiconductor QDs are appealing candidates, assuming the NHMs retain the light absorption and CC photogeneration properties of semiconductor QDs, and the excellent CC transport properties displayed by graphene-like materials. In the current work a solution-processed NHM using PbS quantum dots (QDs) and graphene oxide (GO) was fabricated in a layer-by-layer configuration by dip-coating. Afterwards, these NHMs were reduced by thermal or chemical methods. Reduction process had a direct impact on the final optoelectronic properties displayed by the NHMs. All reduced samples displayed a decrement in their resistivity, particularly the sample chemically reduced, displaying a 107 fold decrease; mainly attributed to N-doping in the reduced graphene oxide (rGO). The optical absorption coefficients also showed a dependence on the rGO's reduction degree, with reduced samples displaying higher values, and sample thermally reduced at 300 °C showing the highest absorption coefficient, due to the combined absorption of unaltered PbS QDs and the appearance of sp2 regions within rGO. The photogenerated current increased in most reduced samples, displaying the highest photocurrent the sample reduced at 400 °C, presenting a 2500-fold increment compared to the NHM before reduction, attributed to an enhanced CC transfer from PbS QDs to rGO, as a consequence of an improved band alignment between them. These results show clear evidence on how the optoelectronic properties of NHMs based on semiconductor nanoparticles and rGO, can be tuned based on their configuration and the reduction process parameters.

World Trade Organization agreements: a framework for trade in animals and animal products.

This paper will provide an overview of the World Trade Organization's agreements on trade in animals and animal products and of the standards developed by the World Organisation for Animal Health (OIE) for the same purpose. Together, these form an international framework for trade in animals and animal products, which is supplemented by the Agreement on the Application of Sanitary and Phytosanitary Measures (SPS Agreement). In this paper, the authors introduce the main provisions of the SPS Agreement, the role of the OIE international standards, the importance of science and the work of the SPS Committee. The authors also explore the relevance of the Agreement on Technical Barriers to Trade and the Trade Facilitation Agreement.

Cet article donne une vue d'ensemble des accords de l'Organisation mondiale du commerce (OMC) relatifs aux échanges internationaux d'animaux et de produits d'origine animale ainsi que des normes élaborées en la matière par l'Organisation mondiale de la santé animale (OIE). Ces deux corpus normatifs constituent le cadre international applicable aux échanges internationaux d'animaux et de produits d'origine animale, auquel s'ajoute l'Accord de l'OMC sur l'application des mesures sanitaires et phytosanitaires (Accord SPS). Les auteurs expliquent les principales dispositions de l'Accord SPS, le rôle des normes internationales de l'OIE, l'importance de la science ainsi que la teneur des travaux du Comité SPS. Ils examinent également la pertinence de l'Accord sur les obstacles techniques au commerce et de l'Accord sur la facilitation des échanges.

Los autores pasan revista a los acuerdos de la Organización Mundial del Comercio (OMC) que encuadran el comercio de animales y productos de origen animal y a las normas elaboradas con el mismo objetivo por la Organización Mundial de Sanidad Animal (OIE). Estos textos forman en conjunto un ordenamiento internacional en el que se inscribe este comercio y que se complementa con el Acuerdo de la OMC sobre la Aplicación de Medidas Sanitarias y Fitosanitarias (Acuerdo MSF). Los autores exponen las principales disposiciones del Acuerdo MSF y la función de las normas internacionales de la OIE, así como el papel de la ciencia al respecto y la labor del Comité de Medidas Sanitarias y Fitosanitarias (Comité MSF). Además, examinan la pertinencia del Acuerdo sobre Obstáculos Técnicos al Comercio y el Acuerdo sobre Facilitación del Comercio.

Evaluation of functionality of type II toxin-antitoxin systems of Clostridioides difficile R20291.

Clostridioides difficile is a nosocomial, Gram-positive, strictly anaerobic, spore-forming pathogen capable of colonizing and proliferating in the human intestine. In bacteria, it has been shown that the Toxin-Antitoxin systems mediate the cellular response to external stress by initiating processes such as biofilm formation and programmed cell death. This work aims to evaluate the functionality of four type II TA modules of Clostridioides difficile R20291. We performed bioinformatic analysis to search for putative TA systems using the TADB platform. Then we performed a heterologous expression assay to evaluate the functionality of these systems. Our results showed that the MazEF and RelBE systems were functional, suggesting that their corresponding toxins possess an endoribonuclease activity. In conclusion, MazEF and RelBE systems of C. difficile R20291 are functional in a heterologous expression system.

Efficacy of 1-day vs. 2-day intestinal preparation using peg 3350 + Bisacodyl: A randomized clinical trial. / Eficacia de la preparación intestinal con un día de PEG 3350 + bisacodilo en comparación con dos días: ensayo clínico aleatorizado.

OBJECTIVE: The objective was to compare the efficacy of 1-day intestinal preparation for colonoscopy using PEG 3350 (polyethylene glycol) (4 g/kg/day) + bisacodyl vs. 2-day intestinal preparation using PEG 3350 (2 g/kg/day) + bisacodyl in pediatric patients. MATERIALS AND METHODS: A blind, randomized clinical trial was carried out with endoscopists who assessed colon cleansing. Patients aged 2-18 years old undergoing scheduled colonoscopy were included. They were randomized into 2 groups: 1-day preparation using PEG 3350 (4 g/kg/day) + bisacodyl, and 2-day preparation using PEG 3350 (2 g/kg/day) + bisacodyl. Endoscopic evaluation (Boston Scale) allowed the efficacy of both preparations to be assessed. Statistical analysis: T of Student for quantitative variables, and Chi square for qualitative variables. RESULTS: 72 patients with a mean age of 94 ± 49 months were included. No significant difference was found between groups regarding preparation difficulty and safety. Efficacy, assessed using the Boston Scale score and the proportion of excellent and good grades achieved, was higher in the 1-day group. Left colon score and total score were higher than in the 2-day group (left colon: 2.20 vs. 1.89, p=0.03; total score: 7.28 vs. 6.76, p=0.01) (left colon: 94.4% vs. 83.4%, p=0.034). CONCLUSIONS: Efficacy in the quality of intestinal preparation for colonoscopy was higher in the 1-day group using PEG 3350 + oral bisacodyl than in the 2-day group.

OBEJTIVO: Comparar la eficacia de la preparación intestinal para colonoscopia con 1 día de preparación con PEG 3350 (polietilenglicol) (4 g/kg/día) + bisacodilo en comparación con 2 días de preparación con PEG 3350 (2 g/kg/día) + bisacodilo en pacientes pediátricos. MATERIAL Y METODOS: Se realizó un ensayo clínico, aleatorizado y cegado para los médicos endoscopistas que evaluaron la limpieza del colon. Se incluyeron pacientes de 2 a 18 años, que ameritaban colonoscopia en forma programada. Se aleatorizaron a los pacientes en dos grupos: 1 día de preparación con PEG 3350 (4 g/kg/día) + bisacodilo y 2 días de preparación con PEG 3350 (2 g/kg/día) + bisacodilo. Por medio de valoración endoscópica (escala de Boston) se determinó la eficacia de las dos preparaciones a evaluar. Análisis estadístico: T de student para cuantitativas y Chi2 para cualitativas. RESULTADOS: Se incluyeron 72 pacientes con edad promedio de 94 ± 49 meses. No hubo diferencia significativa entre los grupos con respecto a la dificultad y seguridad de la preparación. La eficacia, evaluada por el puntaje de la escala de Boston y la proporción de calificación excelente o buena, fue mejor en el grupo de un 1 día, el colon izquierdo y el puntaje total fue mejor en comparación al grupo de 2 días (colon izquierdo 2,20 vs. 1,89 p= 0,03 y total 7,28 vs. 6,76 p= 0,01) (colon izquierdo 94,4 vs. 83,4% p= 0,034). CONCLUSIONES: La eficacia de la calidad en la preparación intestinal para colonoscopia fue mejor entre el grupo de 1 día con PEG 3350 + bisacodilo vía oral en comparación a la preparación de 2 días.

Eficacia de la preparación intestinal con un día de PEG 3350 + bisacodilo en comparación con dos días: ensayo clínico aleatorizado / Efficacy of 1-day vs. 2-day intestinal preparation using peg 3350 + bisacodyl: A randomized clinical trial

Objetivo: Comparar la eficacia de la preparación intestinal para colonoscopia con 1 día de preparación con PEG 3350 (polietilenglicol) (4 g/kg/día) + bisacodilo en comparación con 2 días de preparación con PEG 3350 (2 g/kg/día) + bisacodilo en pacientes pediátricos. Material y métodos: Se realizó un ensayo clínico, aleatorizado y cegado para los médicos endoscopistas que evaluaron la limpieza del colon. Se incluyeron pacientes de 2 a 18 años, que ameritaban colonoscopia en forma programada. Se aleatorizaron a los pacientes en dos grupos: 1 día de preparación con PEG 3350 (4 g/kg/día) + bisacodilo y 2 días de preparación con PEG 3350 (2 g/kg/día) + bisacodilo. Por medio de valoración endoscópica (escala de Boston) se determinó la eficacia de las dos preparaciones a evaluar. Análisis estadístico: T de student para cuantitativas y Chi2 para cualitativas. Resultados: Se incluyeron 72 pacientes con edad promedio de 94 ± 49 meses. No hubo diferencia significativa entre los grupos con respecto a la dificultad y seguridad de la preparación. La eficacia, evaluada por el puntaje de la escala de Boston y la proporción de calificación excelente o buena, fue mejor en el grupo de un 1 día, el colon izquierdo y el puntaje total fue mejor en comparación al grupo de 2 días (colon izquierdo 2,20 vs. 1,89 p = 0,03 y total 7,28 vs. 6,76 p = 0,01) (colon izquierdo 94,4 vs. 83,4% p = 0,034). Conclusiones: La eficacia de la calidad en la preparación intestinal para colonoscopia fue mejor entre el grupo de 1 día con PEG 3350 + bisacodilo vía oral en comparación a la preparación de 2 días

Objective: The objective was to compare the efficacy of 1-day intestinal preparation for colonoscopy using PEG 3350 (polyethylene glycol) (4 g/kg/day) + bisacodyl vs. 2-day intestinal preparation using PEG 3350 (2 g/kg/day) + bisacodyl in pediatric patients. Materials and methods: A blind, randomized clinical trial was car-ried out with endoscopists who assessed colon cleansing. Patients aged 2-18 years old undergoing scheduled colonoscopy were included. They were randomized into 2 groups: 1-day preparation using PEG 3350 (4 g/kg/day) + bisacodyl, and 2-day preparation using PEG 3350 (2 g/kg/day) + bisacodyl. Endoscopic evaluation (Boston Scale) allowed the efficacy of both preparations to be assessed. Statistical analysis: T of Student for quantitative variables, and Chi square for qualitative variables. Results: 72 patients with a mean age of 94 ± 49 months were included. No significant difference was found between groups regarding preparation difficulty and safety. Efficacy, assessed using the Boston Scale score and the proportion of excellent and good grades achieved, was higher in the 1-day group. Left colon score and total score were higher than in the 2-day group (left colon: 2.20 vs. 1.89, p = 0.03; total score: 7.28 vs. 6.76, p = 0.01) (left colon: 94.4% vs. 83.4%, p = 0.034). Conclusions: Efficacy in the quality of intestinal preparation for colonoscopy was higher in the 1-day group using PEG 3350 + oral bisacodyl than in the 2-day group

Estimation of the lateral dimensions of epitaxial submonolayer CdSe/ZnSe quantum dots.

CdSe fractional monolayer quantum dots (FMQDs) embedded in a ZnSe matrix were produced by atomic layer epitaxy with a nominal coverage of 0.5 monolayer. They have a thickness of a/2, where a is the strained perpendicular lattice constant of cubic CdSe. Their photoluminescence spectra at low temperature exhibit narrow and intense excitonic emission around 2.759 eV. Based on the experimental excitonic emission energy and applying the factorized-envelope approximation, we have estimated that the lateral dimensions of these FMQDs are around 4-5 nm and their density is [Formula: see text] cm-2.

Study protocol to investigate biomolecular muscle profile as predictors of long-term urinary incontinence in women with gestational diabetes mellitus.

BACKGROUND: Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated. METHODS: The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24-26 weeks, with a follow-up at 34-38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24-48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. DISCUSSION: To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.

Morphological changes in rat rectus abdominis muscle induced by diabetes and pregnancy.

The urethral muscle of diabetic pregnant rats is affected by long-term mild diabetes and short-term severe diabetes, which plays a crucial role in the pathogenesis of pelvic floor disorders. We hypothesized that muscles outside the pelvis are subject to similar changes. The current study aimed at analyzing the effects of long-term mild and short-term severe diabetes on the structure and ultrastructure of fiber muscles and collagen in rats' rectus abdominis (RA) muscle. Therefore, the RA muscle of virgin, pregnant, long-term mild diabetic, short-term severe diabetic, long-term mild diabetic pregnant and short-term severe diabetic pregnant 3-month-old Wistar rats were collected. The structure was analyzed by picrosirius red staining, immunohistochemistry for fast and slow muscle fibers and transmission electron microscopy. We investigated two levels of STZ- induced diabetes: long-term mild diabetes (blood glucose level: 120-200 mg/dL) and short-term severe diabetes (blood glucose level >300 mg/dL). Long-term mild diabetic pregnant and short-term severe diabetic pregnant rats had decreased fast fibers and increased slow fibers, disrupted areas of sarcomere, intermyofibrillar mitochondria and myelin figures in the RA muscle. Both groups enabled us to analyze the specific influence of pregnancy, separately from diabetes. The current study demonstrated that diabetes and pregnancy induced intramuscular transformation and reorganization of RA muscle with a switch of fiber type adjusting their architecture according to intensity and duration of hyperglycemic insult within pregnancy.

Síndrome de Guillain-Barré: viejos y nuevos conceptos / Guillain-Barre syndrome: older and news concepts

Resumen: En la actualidad el síndrome de Guillain-Barré (SGB) es la causa más frecuente de parálisis flácida aguda. La forma clásica de síndrome no ha sufrido modificaciones importantes en su comportamiento clínico; sin embargo, el espectro de variantes clínicas del síndrome es extenso, sustentado en los avances de la biología molecular y la inmunología que han permitido caracterizar mejor estas formas del síndrome de Guillain-Barré. Los anticuerpos anti-gangliósidos han reestructurado los criterios porque aumentan la sensibilidad y la especificidad del diagnóstico; debido a ello, los criterios clásicos son insuficientes para lograr una adecuada clasificación y discriminar los imitadores del síndrome. La evolución de los criterios debe cambiar la perspectiva en el abordaje del cuadro y normar la conducta terapéutica, sin sobrepasar el juicio clínico de la práctica médica diaria.

Abstract: Currently, Guillain-Barre syndrome (GBS) is the most frequent cause of acute flaccid paralysis. The classical form of syndrome has not undergone major changes in their clinical behavior; however, the spectrum of clinical variants of the syndrome is extensive, supporting advances in molecular biology and immunology have allowed better characterize these forms of GBS. The anti-ganglioside antibodies have restructured the criteria because they increase the sensitivity and specificity of diagnosis; because of this, the traditional criteria are inadequate for appropriated classification and discriminate imitators of the syndrome. The evolution of the criteria should change the perspective in addressing the box and regulate the therapeutic approach, without exceeding the clinical trial of daily medical practice.

Molecular insights into fosfomycin resistance in Escherichia coli.

Objectives: Fosfomycin activity in Escherichia coli depends on several genes of unknown importance for fosfomycin resistance. The objective was to characterize the role of uhpT , glpT , cyaA and ptsI genes in fosfomycin resistance in E. coli. Methods: WT E. coli BW25113 and null mutants, Δ uhpT , Δ glpT , Δ cyaA , Δ ptsI , Δ glpT-uhpT , Δ glpT-cyaA , Δ glpT-ptsI , Δ uhpT-cyaA , Δ uhpT-ptsI and Δ ptsI-cyaA , were studied. Susceptibility to fosfomycin was tested using CLSI guidelines. Fosfomycin mutant frequencies were determined at concentrations of 64 and 256 mg/L. Fosfomycin in vitro activity was tested using time-kill assays at concentrations of 64 and 307 mg/L (human C max ). Results: Fosfomycin MICs were: WT E. coli BW25113 (2 mg/L), Δ glpT (2 mg/L), Δ uhpT (64 mg/L), Δ cyaA (8 mg/L), Δ ptsI (2 mg/L), Δ glpT-uhpT (256 mg/L), Δ glpT-cyaA (8 mg/L), Δ glpT-ptsI (2 mg/L), Δ uhpT-cyaA (512 mg/L), Δ uhpT-ptsI (64 mg/L) and Δ ptsI-cyaA (32 mg/L). In the mutant frequency assays, no mutants were recovered from BW25113. Mutants appeared in Δ glpT , Δ uhpT , Δ cyaA and Δ ptsI at 64 mg/L and in Δ uhpT and Δ cyaA at 256 mg/L. Δ glpT-ptsI , but not Δ glpT-cyaA , Δ uhpT-cyaA or Δ uhpT-ptsI , increased the mutant frequency compared with the highest frequency found in each single mutant. In time-kill assays, all mutants regrew at 64 mg/L. Initial bacterial reductions of 2-4 log 10 cfu/mL were observed for all strains, except for Δ uhpT-ptsI , Δ glpT-uhpT and Δ uhpT-cyaA . Only Δ glpT and Δ ptsI mutants were cleared using 307 mg/L. Conclusions: Fosfomycin MIC may not be a good efficacy predictor, as highly resistant mutants may appear, depending on other pre-existing mutations with no impact on MIC.

Self-organised silicide nanodot patterning by medium-energy ion beam sputtering of Si(100): local correlation between the morphology and metal content.

We have produced self-organised silicide nanodot patterns by medium-energy ion beam sputtering (IBS) of silicon targets with a simultaneous and isotropic molybdenum supply. Atomic force microscopy (AFM) studies show that these patterns are qualitatively similar to those produced thus far at low ion energies. We have determined the relevance of the ion species on the pattern ordering and properties. For the higher ordered patterns produced by Xe(+) ions, the pattern wavelength depends linearly on the ion energy. The dot nanostructures are silicide-rich as assessed by x-ray photoelectron spectroscopy (XPS) and emerge in height due to their lower sputtering yield, as observed by electron microscopy. Remarkably, a long wavelength corrugation is observed on the surface which is correlated with both the Mo content and the dot pattern properties. Thus, as assessed by electron microscopy, the protrusions are Mo-rich with higher and more spaced dots on their surface whereas the valleys are Mo-poor with smaller dots that are closer to each other. These findings indicate that there is a correlation between the local metal content of the surface and the nanodot pattern properties both at the nanodot and the large corrugation scales. These results contribute to advancing the understanding of this interesting nanofabrication method and aid in developing a comprehensive theory of nanodot pattern formation and evolution.

Salmonella Typhimurium exhibits fluoroquinolone resistance mediated by the accumulation of the antioxidant molecule H2S in a CysK-dependent manner.

OBJECTIVES: To evaluate the contribution of cysK and cysM to the fluoroquinolone (ofloxacin) antibiotic resistance in Salmonella Typhimurium, and their impact on H2S and cysteine production through targeted mutagenesis. METHODS: Salmonella Typhimurium 14028s and its cysK and cysM mutants were tested for their susceptibility to ofloxacin, as determined by a broth microdilution test (to determine the MIC) and survival curves. H2S levels were measured by the Pb(AC)2 method and cysteine levels were determined using 5,5-dithio-bis-2-nitrobenzoic acid. DNA damage induced by antibiotic treatment was determined by PFGE. Finally, expression of cysK and cysM genes under antibiotic treatment was determined by real-time reverse transcription PCR. RESULTS: As determined by MIC, the ΔcysK strain was more resistant to ofloxacin, a reactive oxygen species (ROS)-producing fluoroquinolone, than the WT and ΔcysM strains, which correlates with survival curves. Moreover, the ΔcysK strain exhibited higher H2S levels and lower cysteine levels than the WT strain. Finally, the ΔcysK strain exhibited lower DNA damage upon challenge with ofloxacin than the WT and ΔcysM strains. These results are in accordance with lower expression of cysK under ofloxacin treatment in the WT strain. CONCLUSIONS: This work demonstrated that cysteine metabolism in Salmonella Typhimurium modulated H2S levels, conferring resistance to second-generation fluoroquinolones.

Lose to win: marT pseudogenization in Salmonella enterica serovar Typhi contributed to the surV-dependent survival to H2O2, and inside human macrophage-like cells.

The difference in host range between Salmonella enterica serovar Typhimurium (S. Typhimurium) and Salmonella enterica serovar Typhi (S. Typhi) can be partially attributed to the gain of functions, to the loss of functions (i.e. pseudogenization), or to a combination of both processes. As previously reported, the loss of functions by pseudogenization may play a role in bacterial evolution, especially in host-restricted pathogens such as S. Typhi. The marT-fidL operon, located at the SPI-3, encodes the MarT transcriptional regulator and a hypothetical protein (i.e. FidL) with no significant similarities to known proteins, respectively. Even though predicted S. Typhimurium FidL exhibit 99.4% identity with S. Typhi FidL, marT has been annotated as a pseudogene in S. Typhi. In this work, we found that S. Typhi expressing S. Typhimurium marT-fidL exhibited an increased accumulation of reactive oxygen species (ROS), leading to a decreased survival in presence of H2O2. Moreover, we found that that the presence of a functional copy of S. Typhimurium marT-fidL in S. Typhi resulted in a repression of surV (STY4039), an ORF found in the S. Typhi SPI-3 but absent from S. Typhimurium SPI-3, that contribute to the resistance to H2O2 by decreasing the accumulation of ROS. Finally, we observed that the presence of S. Typhimurium marT-fidL in S. Typhi negatively affected the survival inside macrophage-like cells, but not in epithelial cells, after 24h post infection. Therefore, this work provides evidence arguing that marT pseudogenization in Salmonella Typhi contributed to the surV-dependent survival against H2O2, and inside human macrophage-like cells. This is a good example of how the loss of functions (marT pseudogenization) and the gain of functions (presence of surV) might contribute to phenotypic changes improving virulence.

Maternal-Foetal Diabetes Modifies Neonatal Fc Receptor Expression on Human Leucocytes.

This study investigated the expression of the neonatal Fc receptor (FcRn) in maternal blood, cord blood and placental cells and determined IgG levels in maternal blood and cord blood from diabetic mothers. Peripheral blood, cord blood and placenta samples were collected from 26 mothers with normoglycaemia (non-diabetic, ND group) and 52 with hyperglycaemia (26 with mild gestational hyperglycaemia, MGH group, and 26 with type 2 diabetes mellitus, DM-2 group). Cells expressing CD19(+) and FcRn were identified by flow cytometry. Total IgG and its subclasses were quantified by ELISA. Maternal blood from DM-2 and cord blood from MGH exhibited a higher proportion of CD19(+) expression by B cells. DM-2 showed a lower proportion of CD19(+) cells in placenta. FcRn expression increased in cells from cord blood and placenta from MGH. Maternal blood, cord blood and placenta cells from DM-2 showed lower FcRn expression. Blood IgG levels were lower in DM-2, and cord blood IgG levels were higher in MGH. The highest levels of IgG4 were detected in the blood of hyperglycaemic mothers. The highest IgG3 and IgG4 levels in cord blood were detected in MGH, and the lowest IgG2 and IgG3 levels in DM-2. Maternal hyperglycaemia compromised placental transfer of IgG1, IgG3 and IgG4. The results suggest that regardless of hyperglycaemia degree, it decreases FcRn expression in placenta and blood cells and compromises the production and transfer of antibodies from maternal blood to newborns.