Mathematical Model of Plasmid-Mediated Resistance to Ceftiofur in Commensal Enteric Escherichia coli of Cattle

Antimicrobial use in food animals may contribute to antimicrobial resistance in bacteria of animals and humans. Commensal bacteria of animal intestine may serve as a reservoir of resistance-genes. To understand the dynamics of plasmid-mediated resistance to cephalosporin ceftiofur in enteric commensals of cattle, we developed a deterministic mathematical model of the dynamics of ceftiofur-sensitive and resistant commensal enteric Escherichia coli (E. coli) in the absence of and during parenteral therapy with ceftiofur. The most common treatment scenarios including those using a sustained-release drug formulation were simulated; the model outputs were in agreement with the available experimental data. The model indicated that a low but stable fraction of resistant enteric E. coli could persist in the absence of immediate ceftiofur pressure, being sustained by horizontal and vertical transfers of plasmids carrying resistance-genes, and ingestion of resistant E. coli. During parenteral therapy with ceftiofur, resistant enteric E. coli expanded in absolute number and relative frequency. This expansion was most influenced by parameters of antimicrobial action of ceftiofur against E. coli. After treatment (>5 weeks from start of therapy) the fraction of ceftiofur-resistant cells among enteric E. coli, similar to that in the absence of treatment, was most influenced by the parameters of ecology of enteric E. coli, such as the frequency of transfer of plasmids carrying resistance-genes, the rate of replacement of enteric E. coli by ingested E. coli, and the frequency of ceftiofur resistance in the latter

Constitutive Activation of PrfA Tilts the Balance of Listeria monocytogenes Fitness Towards Life within the Host versus Environmental Survival

PrfA is a key regulator of Listeria monocytogenes pathogenesis and induces the expression of multiple virulence factors within the infected host. PrfA is post-translationally regulated such that the protein becomes activated upon bacterial entry into the cell cytosol. The signal that triggers PrfA activation remains unknown, however mutations have been identified (prfA* mutations) that lock the protein into a high activity state. In this report we examine the consequences of constitutive PrfA activation on L. monocytogenes fitness both in vitro and in vivo. Whereas prfA* mutants were hyper-virulent during animal infection, the mutants were compromised for fitness in broth culture and under conditions of stress. Broth culture prfA*-associated fitness defects were alleviated when glycerol was provided as the principal carbon source; under these conditions prfA* mutants exhibited a competitive advantage over wild type strains. Glycerol and other three carbon sugars have been reported to serve as primary carbon sources for L. monocytogenes during cytosolic growth, thus prfA* mutants are metabolically-primed for replication within eukaryotic cells. These results indicate the critical need for environment-appropriate regulation of PrfA activity to enable L. monocytogenes to optimize bacterial fitness inside and outside of host cells

Cytoskeletal control of B cell responses to antigens.

The actin cytoskeleton is essential for cell mechanics and has increasingly been implicated in the regulation of cell signalling. In B cells, the actin cytoskeleton is extensively coupled to B cell receptor (BCR) signalling pathways, and defects of the actin cytoskeleton can either promote or suppress B cell activation. Recent insights from studies using single-cell imaging and biophysical techniques suggest that actin orchestrates BCR signalling at the plasma membrane through effects on protein diffusion and that it regulates antigen discrimination through the biomechanics of immune synapses. These mechanical functions also have a role in the adaptation of B cell subsets to specialized tasks during antibody responses

Estudio epidemiológico sobre el impacto de la pandemia COVID-19 en la salud mental de la población de Lima Metropolitana

Objetivo: Identificar en la población adulta de la Lima Metropolitana la prevalencia, acceso y factores asociados a los principales trastornos mentales (TM) durante la pandemia COVID-19. Metodología: Estudio transversal, correlacional en una muestra probabilística, bietápica, de 1823 personas adultas (≥18 años), entrevistada vía telefónica. Instrumentos: Ficha sociodemográfica y características de vivienda; Cuestionario sobre Experiencias COVID-19; la MINI International Neuropsychiatric Interview Versión CIE-10; la Escala de Riesgo Suicida del MINI; el Índice de Calidad de Sueño de Pittsburgh; Escala de Percepción de Estrés; Escala Breve de Funcionamiento Psicosocial (basada en áreas sugeridas del WHO DAS-S); Cuestionario sobre Acceso a Servicios de Salud; Índice de Calidad de Vida de Mezzich; Escala de Satisfacción con la Vida de Diener; Escala de Resiliencia del Yo de Block; y un Cuestionario Abreviado Ad-hoc sobre Violencia Doméstica. Se utilizó la F corregida como una variante del estadístico de chi-cuadrado corregido de Rao-Scott de segundo orden y análisis de regresión logística para muestras complejas. Resultados: Se encontró en un 57,2% de la población un nivel de estrés de moderado a severo. La mayoría de los indicadores de salud mental, incluyendo de salud positiva, mostraron resultados desfavorables con respecto a estudios previos, incluyendo indicadores suicidas, problemas de sueño y la violencia sistemática contra la mujer. La prevalencia a 12 meses, 6 meses y actual de algún TM fue del 19,6%, 17,8% y 12,5%, respectivamente. El TM más frecuente fue el episodio depresivo con una prevalencia anual de 13,6% y de 6 meses de 12,3%, seguido por el trastorno de ansiedad generalizada. La presencia de TM se asoció significativamente con el sexo femenino, menor edad, estado civil viudo(a), divorciado(a) o separado(a), un menor nivel educativo, baja situación económica, haber perdido el empleo por la pandemia, haberse contagiado de la COVID-19, tener un familiar contagiado y tener un familiar fallecido por COVID. De la misma manera las personas afectadas por la COVID-19 presentaron resultados desfavorables en los todos los indicadores de salud mental. El 12,2% de las personas con TM diagnosticables fue atendida, y 29,4% consideró haber necesitado bastante o mucha atención, pero no la recibió. Conclusiones: En comparación a períodos sin pandemia, se ha encontrado un incremento desfavorable de los indicadores de salud mental que obliga a asumir que uno de los principales efectos de la pandemia sería sobre la salud mental de las personas y, por lo tanto, las políticas sociales deberían orientarse con prioridad en este aspecto