In vitro activity of cefiderocol and other newly approved antimicrobials against multi-drug resistant Gram-negative pathogens recovered in intensive care units in Spain and Portugal.

OBJECTIVE: The antimicrobial resistance is a significant public health threat, particularly for healthcare-associated infections caused by carbapenem-resistant Gram-negative pathogens which are increasingly reported worldwide. The aim of this study was to provide data on the in vitro antimicrobial activity of cefiderocol and that of commercially available comparator antibiotics against a defined collection of recent clinical multi-drug resistant (MDR) microorganisms, including carbapenem resistant Gram-negative bacteria collected from different regions in Spain and Portugal. METHODS: A total of 477 clinical isolates of Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia were prospectively (n=265) and retrospectively (n=212) included (2016-2019). Susceptibility testing was performed using standard broad microdilution and results were interpreted using CLSI-2021 and EUCAST-2021 criteria. RESULTS: Overall, cefiderocol showed a good activity against Enterobacterales isolates, being 99.5% susceptible by CLSI and 94.5% by EUCAST criteria. It also demonstrated excellent activity against P. aeruginosa and S. maltophilia isolates, all being susceptible to this compound considering CLSI breakpoints. Regarding A. baumannii (n=64), only one isolate was resistant to cefiderocol. CONCLUSIONS: Our results are in agreement with other studies performed outside Spain and Portugal highlighting its excellent activity against MDR gram-negative bacteria. Cefiderocol is a therapeutic alternative to those available for the treatment of infections caused by these MDR bacteria.

Studies of the transition between amplified spontaneous emission and optical lasing in ultrahigh-Q polymeric micro-pedestals.

In this work, we demonstrate the properties of Rhodamine B-doped polymeric cylindrical microlasers to perform either as gain amplification devices through amplified spontaneous emission (ASE) or as optical lasing gain devices. A study based on different %wt concentrations of microcavity families with distinct geometrical features demonstrates the characteristic dependence on either gain amplification phenomena. Principal component analysis (PCA) discriminates the relationship between the main ASE and lasing properties and the geometrical aspects of the cavity families. ASE and optical lasing thresholds were found, respectively, as low as 0.2 µJcm-2 and 0.1 µJcm-2 passing the best-reported microlaser performances in literature for cylindrical cavities, even in comparison with those based on 2D patterns. Moreover, our microlasers showed ultrahigh Q-factor of ∼3 × 106, and for the first time, to the best of our knowledge, a visible emission comb constituted by above a hundred peaks at 40 µJcm-2 with a registered free spectral range (FSR) of 0.25 nm corroborated through the whispery gallery mode (WGM) theory.

Children with psoriasis and COVID-19: factors associated with an unfavourable COVID-19 course, and the impact of infection on disease progression (Chi-PsoCov registry).

BACKGROUND: The COVID-19 pandemic has raised questions regarding the management of chronic skin diseases, especially in patients on systemic treatments. Data concerning the use of biologics in adults with psoriasis are reassuring, but data specific to children are missing. Moreover, COVID-19 could impact the course of psoriasis in children. OBJECTIVES: The aim of this study was therefore to assess the impact of COVID-19 on the psoriasis of children, and the severity of the infection in relation to systemic treatments. METHODS: We set up an international registry of paediatric psoriasis patients. Children were included if they were under 18 years of age, had a history of psoriasis, or developed it within 1 month of COVID-19 and had COVID-19 with or without symptoms. RESULTS: One hundred and twenty episodes of COVID-19 in 117 children (mean age: 12.4 years) were reported. The main clinical form of psoriasis was plaque type (69.4%). Most children were without systemic treatment (54.2%); 33 (28.3%) were on biologic therapies, and 24 (20%) on non-biologic systemic drugs. COVID-19 was confirmed in 106 children (88.3%) and 3 children had two COVID-19 infections each. COVID-19 was symptomatic for 75 children (62.5%) with a mean duration of 6.5 days, significantly longer for children on non-biologic systemic treatments (P = 0.02) and without systemic treatment (P = 0.006) when compared with children on biologics. The six children who required hospitalization were more frequently under non-biologic systemic treatment when compared with the other children (P = 0.01), and particularly under methotrexate (P = 0.03). After COVID-19, the psoriasis worsened in 17 cases (15.2%). Nine children (8%) developed a psoriasis in the month following COVID-19, mainly a guttate form (P = 0.01). DISCUSSION: Biologics appear to be safe with no increased risk of severe form of COVID-19 in children with psoriasis. COVID-19 was responsible for the development of psoriasis or the worsening of a known psoriasis for some children.

Bacterial diversity in high Andean grassland soils disturbed with Lepidium meyenii crops evaluated by metagenomics / Diversidade bacteriana em solos de prados andinos elevados perturbados por culturas de Lepidium meyenii avaliadas por metagenômica

Soil quality is usually determined by its physical-chemical characteristics without taking into account the bacterial communities that play a fundamental role in the chemical decomposition of plant nutrients. In this context, the objective of the study was to evaluate bacterial diversity in high Andean grassland soils disturbed with Lepidium meyenii cultivation under different gradients of use (first, second and third use) and crop development (pre-sowing, hypocotyl development and post-harvest). The sampling was carried out in the Bombón plateau in the central Andes of Peru, during the rainy and low water seasons, by the systematic method based on a specific pattern assigned in a geometric rectangular shape at a depth of 0 - 20 cm. The characterization of the bacterial communities was carried out through the metagenomic sequencing of the 16S rRNA. 376 families of bacteria were reported, of which it was determined that there was a significant change in bacterial composition and distribution in relation to use pressure. There were no major changes due to the development of Lepidium meyenii. The families most sensitive to use pressure and soil poverty indicators were Verrucomicrobiaceae, Acidobacteraceae and Aakkermansiaceae.

A qualidade do solo é normalmente determinada pelas suas características físico-químicas sem ter em conta as comunidades bacterianas que desempenham um papel fundamental na decomposição química dos nutrientes das plantas. Neste contexto, o objetivo do estudo foi avaliar a diversidade bacteriana em solos de prados andinos elevados perturbados pelo cultivo de Lepidium meyenii sob diferentes gradientes de utilização (primeira, segunda e terceira utilizações) e desenvolvimento das culturas (pré-semeadura, desenvolvimento do hipocótilo e pós colheita). A amostragem foi realizada no planalto de Bombón, nos Andes centrais do Peru, durante as estações das chuvas e das águas baixas, pelo método sistemático baseado num padrão específico atribuído em forma geométrica retangular a uma profundidade de 0 - 20 cm. A caracterização das comunidades bacterianas foi realizada através da sequenciação metagenômica do rRNA 16S. Foram relatadas 376 famílias de bactérias, das quais se verificou uma alteração significativa na composição e distribuição bacteriana em relação à pressão de utilização. Não se registaram grandes alterações devido ao desenvolvimento do Lepidium meyenii. As famílias mais sensíveis à utilização de indicadores de pressão e pobreza do solo foram as Verrucomicrobiaceae, Acidobacteraceae e Aakkermansiaceae.

Bacterial diversity in high Andean grassland soils disturbed with Lepidium meyenii crops evaluated by metagenomics

Abstract Soil quality is usually determined by its physical-chemical characteristics without taking into account the bacterial communities that play a fundamental role in the chemical decomposition of plant nutrients. In this context, the objective of the study was to evaluate bacterial diversity in high Andean grassland soils disturbed with Lepidium meyenii cultivation under different gradients of use (first, second and third use) and crop development (pre-sowing, hypocotyl development and post-harvest). The sampling was carried out in the Bombón plateau in the central Andes of Peru, during the rainy and low water seasons, by the systematic method based on a specific pattern assigned in a geometric rectangular shape at a depth of 0 - 20 cm. The characterization of the bacterial communities was carried out through the metagenomic sequencing of the 16S rRNA. 376 families of bacteria were reported, of which it was determined that there was a significant change in bacterial composition and distribution in relation to use pressure. There were no major changes due to the development of Lepidium meyenii. The families most sensitive to use pressure and soil poverty indicators were Verrucomicrobiaceae, Acidobacteraceae and Aakkermansiaceae.

Resumo A qualidade do solo é normalmente determinada pelas suas características físico-químicas sem ter em conta as comunidades bacterianas que desempenham um papel fundamental na decomposição química dos nutrientes das plantas. Neste contexto, o objetivo do estudo foi avaliar a diversidade bacteriana em solos de prados andinos elevados perturbados pelo cultivo de Lepidium meyenii sob diferentes gradientes de utilização (primeira, segunda e terceira utilizações) e desenvolvimento das culturas (pré-semeadura, desenvolvimento do hipocótilo e pós-colheita). A amostragem foi realizada no planalto de Bombón, nos Andes centrais do Peru, durante as estações das chuvas e das águas baixas, pelo método sistemático baseado num padrão específico atribuído em forma geométrica retangular a uma profundidade de 0 - 20 cm. A caracterização das comunidades bacterianas foi realizada através da sequenciação metagenômica do rRNA 16S. Foram relatadas 376 famílias de bactérias, das quais se verificou uma alteração significativa na composição e distribuição bacteriana em relação à pressão de utilização. Não se registaram grandes alterações devido ao desenvolvimento do Lepidium meyenii. As famílias mais sensíveis à utilização de indicadores de pressão e pobreza do solo foram as Verrucomicrobiaceae, Acidobacteraceae e Aakkermansiaceae.

Bacterial diversity in high Andean grassland soils disturbed with Lepidium meyenii crops evaluated by metagenomics / Diversidade bacteriana em solos de prados andinos elevados perturbados por culturas de Lepidium meyenii avaliadas por metagenômica

Soil quality is usually determined by its physical-chemical characteristics without taking into account the bacterial communities that play a fundamental role in the chemical decomposition of plant nutrients. In this context, the objective of the study was to evaluate bacterial diversity in high Andean grassland soils disturbed with Lepidium meyenii cultivation under different gradients of use (first, second and third use) and crop development (pre-sowing, hypocotyl development and post-harvest). The sampling was carried out in the Bombón plateau in the central Andes of Peru, during the rainy and low water seasons, by the systematic method based on a specific pattern assigned in a geometric rectangular shape at a depth of 0 - 20 cm. The characterization of the bacterial communities was carried out through the metagenomic sequencing of the 16S rRNA. 376 families of bacteria were reported, of which it was determined that there was a significant change in bacterial composition and distribution in relation to use pressure. There were no major changes due to the development of Lepidium meyenii. The families most sensitive to use pressure and soil poverty indicators were Verrucomicrobiaceae, Acidobacteraceae and Aakkermansiaceae.

A qualidade do solo é normalmente determinada pelas suas características físico-químicas sem ter em conta as comunidades bacterianas que desempenham um papel fundamental na decomposição química dos nutrientes das plantas. Neste contexto, o objetivo do estudo foi avaliar a diversidade bacteriana em solos de prados andinos elevados perturbados pelo cultivo de Lepidium meyenii sob diferentes gradientes de utilização (primeira, segunda e terceira utilizações) e desenvolvimento das culturas (pré-semeadura, desenvolvimento do hipocótilo e póscolheita). A amostragem foi realizada no planalto de Bombón, nos Andes centrais do Peru, durante as estações das chuvas e das águas baixas, pelo método sistemático baseado num padrão específico atribuído em forma geométrica retangular a uma profundidade de 0 - 20 cm. A caracterização das comunidades bacterianas foi realizada através da sequenciação metagenômica do rRNA 16S. Foram relatadas 376 famílias de bactérias, das quais se verificou uma alteração significativa na composição e distribuição bacteriana em relação à pressão de utilização. Não se registaram grandes alterações devido ao desenvolvimento do Lepidium meyenii. As famílias mais sensíveis à utilização de indicadores de pressão e pobreza do solo foram as Verrucomicrobiaceae, Acidobacteraceae e Aakkermansiaceae.

Bacterial diversity in high Andean grassland soils disturbed with Lepidium meyenii crops evaluated by metagenomics.

Soil quality is usually determined by its physical-chemical characteristics without taking into account the bacterial communities that play a fundamental role in the chemical decomposition of plant nutrients. In this context, the objective of the study was to evaluate bacterial diversity in high Andean grassland soils disturbed with Lepidium meyenii cultivation under different gradients of use (first, second and third use) and crop development (pre-sowing, hypocotyl development and post-harvest). The sampling was carried out in the Bombón plateau in the central Andes of Peru, during the rainy and low water seasons, by the systematic method based on a specific pattern assigned in a geometric rectangular shape at a depth of 0 - 20 cm. The characterization of the bacterial communities was carried out through the metagenomic sequencing of the 16S rRNA. 376 families of bacteria were reported, of which it was determined that there was a significant change in bacterial composition and distribution in relation to use pressure. There were no major changes due to the development of Lepidium meyenii. The families most sensitive to use pressure and soil poverty indicators were Verrucomicrobiaceae, Acidobacteraceae and Aakkermansiaceae.

Low-cost fabrication of microlasers based on polymeric micropedestals.

Our current work exploits direct laser writing (DLW) and low one-photon absorption (LOPA) in a low-cost three-dimensional optical fabrication system designed to print micrometric polymeric structures. Micropedestals were obtained by focusing a laser beam on a photoresist layer deposited on a silica glass substrate. Subsequent coating with rhodamine 6G dye allows these pedestals to function as microlasers upon optical excitation at 532 nm. Our microlasers, with a diameter of ∼53µm and a height of ∼40µm, exhibit a broad fluorescence peak in the spectral range 540-600 nm, in addition to narrow lasing peaks, exhibiting quality factors Q exceeding 2000 and a lasing threshold of ∼5µJcm-2. The observed free spectral range associated with the lasing peaks of ∼1.3nm is consistent with simulations, which we include in this paper. In addition, we present simulations for the longitudinal shift of the patterning laser spot, which occurs particularly for relatively thick photoresist layers, coupled with a large index contrast at the photoresist top surface. Such a shift could introduce errors in the resulting microfabricated structures if left unaccounted for. We hope that our work will contribute to the development of microlasers for various photonic applications, particularly if dimensions can be reduced, for on-chip optical communications and data processing.

Pantoea agglomerans como marcador de cáncer en pacientes inmunodeprimidos / Pantoea agglomerans as a cancer hallmark in immunocompromised patients

Pantoea agglomerans es un bacilo gramnegativo reportado principalmente en heridas penetrantes, infecciones neonatales o como contaminante. La infección relevante por esta bacteria es rara. Nuestra revisión de la literatura sugirió una asociación consistente entre la infección por Pantoea agglomerans en pacientes inmunodeprimidos y una neoplasia maligna previamente diagnosticada. Los autores describen un derrame pleural paraneumónico en el que el aislamiento de Pantoea agglomerans permitió el diagnóstico de novo de cáncer de pulmón

Pantoea agglomerans is a gram-negative rod reported mainly in penetrating wounds, neonatal infections or as a contaminant. Relevant infection by this bacterium is rare. Our review of available literature suggested a consistent association between Pantoea agglomerans infection in immunocompromised patients and previously diagnosed malignancy. The authors describe a parapneumonic pleural effusion in which the isolation of Pantoea agglomerans allowed for de novo diagnosis of lung cancer

Blockade of dopamine D2 receptors disrupts intrahippocampal connectivity and enhances pain-related working memory deficits in neuropathic pain rats.

BACKGROUND: Dopamine (DA) is thought to be important to local hippocampal networks integrity during spatial working memory (sWM) processing. Chronic pain may contribute to deficient dopaminergic signalling, which may in turn affect cognition. However, the neural mechanisms that determine this impairment are poorly understood. Here, we evaluated whether the sWM impairment characteristic of animal models of chronic pain is dependent on DA D2 receptor (D2r) activity. METHODS: To address this issue, we implanted multichannel arrays of electrodes in the dorsal and ventral hippocampal CA1 field (dvCA1) of rats and recorded the neuronal activity during a classical delayed food-reinforced T-maze sWM task. Within-subject behavioural performance and patterns of dorsoventral neural activity were assessed before and after the onset of persistent neuropathic pain using the spared nerve injury (SNI) model. RESULTS: Our results show that the peripheral nerve lesion caused a disruption in sWM and hippocampus spike activity and that disruption was maximized by the systemic administration of the D2r antagonist raclopride. These deficits are strictly correlated with a selective disruption of hippocampal theta-oscillations. Particularly, we found a significant decrease in intrahippocampal CA1 field connectivity level. CONCLUSIONS: Together, these results suggest that disruption of the dopaminergic balance in the intrahippocampal networks may be important for the development of cognitive deficits experienced during painful conditions. SIGNIFICANCE: This study provides new insights into the role of D2r in the manifestation of pain-related sWM deficits. Our findings support that selective blockade of D2r produces a significant decrease in intrahippocampal connectivity mediated by theta-oscillations, and amplifies pain-related sWM deficits. These results suggest that further characterization of intrahippocampal dopaminergic modulation may be clinically relevant for the understanding of cognitive impairments that accompanies nociceptive stressful conditions.

The role of epigenetic modifiers in extended cultures of functional hepatocyte-like cells derived from human neonatal mesenchymal stem cells.

The development of predictive in vitro stem cell-derived hepatic models for toxicological drug screening is an increasingly important topic. Herein, umbilical cord tissue-derived mesenchymal stem cells (hnMSCs) underwent hepatic differentiation using an optimized three-step core protocol of 24 days that mimicked liver embryogenesis with further exposure to epigenetic markers, namely the histone deacetylase inhibitor trichostatin A (TSA), the cytidine analogue 5-azacytidine (5-AZA) and dimethyl sulfoxide (DMSO). FGF-2 and FGF-4 were also tested to improve endoderm commitment and foregut induction during Step 1 of the differentiation protocol, being HHEX expression increased with FGF-2 (4 ng/mL). DMSO (1%, v/v) when added at day 10 enhanced cell morphology, glycogen storage ability, enzymatic activity and induction capacity. Moreover, the stability of the hepatic phenotype under the optimized differentiation conditions was examined up to day 34. Our findings showed that hepatocyte-like cells (HLCs) acquired the ability to metabolize glucose, produce albumin and detoxify ammonia. Global transcriptional analysis of the HLCs showed a partial hepatic differentiation degree. Global analysis of gene expression in the different cells revealed shared expression of gene groups between HLCs and human primary hepatocytes (hpHeps) that were not observed between HepG2 and hpHeps. In addition, bioinformatics analysis of gene expression data placed HLCs between the HepG2 cell line and hpHeps and distant from hnMSCs. The enhanced hepatic differentiation observed was supported by the presence of the hepatic drug transporters OATP-C and MRP-2 and gene expression of the hepatic markers CK18, TAT, AFP, ALB, HNF4A and CEBPA; and by their ability to display stable UGT-, EROD-, ECOD-, CYP1A1-, CYP2C9- and CYP3A4-dependent activities at levels either comparable with or even higher than those observed in primary hepatocytes and HepG2 cells. Overall, an improvement of the hepatocyte-like phenotype was achieved for an extended culture time suggesting a role of the epigenetic modifiers in hepatic differentiation and maturation and presenting hnMSC-HLCs as an advantageous alternative for drug discovery and in vitro toxicology testing.

Mass, nutrient pool, and mineralization of litter and fine roots in a tropical mountain cloud forest.

We used fine root and litter mass from a tropical mountain cloud forest to assess their relative contribution to nutrient content and to examine mineralization processes during a laboratory incubation experiment. Our results showed that average fine root mass density ranged from 2.86kgm-3 to 11.59kgm-3, while litter mass density ranged from 72.5kgm-3 to 177.3kgm-3. On average, fine root mass density represented 4.7% of the mass density of the O horizon. Fine root mass density followed an exponentially declining trend with soil depth. On average, 83% of fine root mass density within the soil profile was concentrated in the O horizon. Mean element pools in litter decreased from 44.08mgcm-3 to 0.49µgcm-3 in the following sequence: C>N>Fe>S>Ca>P>K>Mg>Na>Mn>Zn>Cu. For fine roots, a different mean element pool sequence (C>N>Ca>K>Fe>S>Mg>Na>P>Mn>Zn>Cu) in decreasing abundance (from 2.88mgcm-3 to 0.13µgcm-3) was observed with respect to litter. Regarding C, litter mineralized faster than fine roots, with a mean k value of 0.25d-1 for litter and 0.13d-1 for fine roots. Principal component analysis (PCA) combined with stepwise regression analysis revealed that the main mass density predictors were N, S, Zn, and Mn for litter (p<0.0001, R2=0.92), and S and C/N ratio for fine roots (p<0.0001, R2=0.82). These results demonstrate the potential of chemical composition to influence the mineralization of fine root and litter mass and therefore the nutrient availability and C sequestration.

Intercambiabilidad entre el método por auscultación y por dispositivo electrónico automático de la presión arterial media en mujeres embarazadas sin hipertensión. Estudio piloto / Auscultation and automated electronic blood pressure device interchangeability in non-hypertensive pregnant women. A pilot study

Resumen OBJETIVO: definir el tamaño de muestra necesario para evaluar la intercambiabilidad entre el método por auscultación y por dispositivo electrónico automático de la presión arterial media en mujeres embarazadas sin hipertensión. MATERIALES Y MÉTODOS: estudio piloto, observacional, efectuado en mujeres embarazadas sin hipertensión. La medición estandarizada de la presión arterial se efectuó por los dos métodos en ambos brazos y se calculó el coeficiente de correlación entre las presiones arteriales medias combinadas; el IC95% inferior se utilizó para el cálculo necesario de la muestra final. RESULTADOS: se estudiaron 30 pacientes en quienes la correlación entre métodos tuvo una r = 0.557 (IC95% 0.246; 0.763, p = 0.001 y r2 = 0.3097). CONCLUSIONES: la correlación entre métodos, aunque estadísticamente significativa, podría ser clínicamente inaceptable para fines de intercambiabilidad. Para probarlo se requiere un tamaño de muestra con n = 127.

Abstract OBJECTIVE: To define the sample size needed to evaluate exchangeability between the auscultation method and the automated electronic device for MAP measurement in pregnancies without hypertension. MATERIALS AND METHODS: A standardized blood pressure measurement on both arms, and by both methods was performed on 30 pregnancies without hypertension; the combined MAP correlation coefficient was calculated, using the lower CI95% for final sample size needed. RESULTS: Correlation between methods was r = 0.557 (CI95% = 0.246; 0.763, p = 0.001 and r2 = 0.3097). CONCLUSIONS: The statistically significant correlation between methods could be clinically unacceptable for exchangeability; a sample size of n = 127 is needed to prove it.

Corrección de medianas de la fracción beta libre de gonadotrofina coriónica humana y proteína plasmática A del embarazo del primer trimestre para una muestra de población mexicana / Medians correction of free beta subunit of human chorionic gonadotropin and pregnancy-associated plasma protein-A during the first trimester for a Mexican population sample

Resumen Objetivo: determinar si en una muestra de población mexicana la distribución de los marcadores séricos del primer trimestre difiere del modelo de riesgos de The Fetal Medicine Foundation y calcular los factores de corrección necesarios para un desempeño adecuado de la prueba. Materiales y Métodos: estudio descriptivo y transversal en el que se midieron las concentraciones de beta-hCG-libre y proteína plasmática A del embarazo en sueros maternos del primer trimestre, por ensayo de electroquimioluminiscencia aprobado por la Fetal Medicine Foundation. Se obtuvieron los múltiplos de mediana ajustados por el algoritmo de la Fetal Medicine Foundation (astraia). Para describir la distribución de cada marcador y probar su diferencia estadística con la media 0.000, se hizo su transformación a log10 ideal mediante la prueba de t para una muestra. Además, se describen las distribuciones de los múltiplos de mediana por características del embarazo y lote de reactivo. Resultados: en 1008 sueros, el log10 MoM global fue de -0.121 ± 0.2706 para beta-hCG-libre y -0.049 ± 0.2372 para proteína plasmática A del embarazo. Conclusiones: en esta muestra poblacional mexicana las distribuciones de beta-hCG-libre y proteína plasmática A del embarazo difieren de las esperadas para población similar a la hispana europea. Se recomienda aplicar los respectivos factores de corrección de 0.756 y de 0.893 para las medianas del algoritmo.

Abstract Objective: To determine whether first trimester serum markers distribution on a Mexican population sample differ from The Fetal Medicine Foundation (FMF) risks model, and to calculate the necessary correction factors for accurate test performance. Materials and Method: Transverse descriptive study, Free-beta-hCG and PAPP-A were measured on unselected first trimester maternal sera using FMF approved electrochemiluminescence assay, the adjusted MoM were obtained from FMF algorithm (astraia); they were log10 transformed to describe each marker distribution and to test their statistical difference with the 0.000 ideal mean by one sample t-test. MoM distributions for pregnancy characteristics and reagent lot are additionally described. Results: On 1008 sera, the overall adjusted log10MoM was -0.121 ± 0.2706 SD for Free-beta-hCG and -0.049 ± 0.2372 SD for PAPP-A; these distributions differed significantly from tåzhe expected by FMF risks model. Conclusions: Free-beta-hCG and PAPP-A distributions on this Mexican population sample differ from expected for population similar to Hispanic European, median correction factors of 0.756 MoM and of 0.893 MoM, respectively, are recommended for the algorithm.

Falta de evidencia en la determinación de la isoenzima BB de la fosforilasa de glucógeno (GPBB) como prueba diagnóstica de preeclampsia / Lack of evidence for offering the qualitative determination of glycogen phosphorylase isoenzyme BB (GPBB) in capillary blood of pregnant women as diagnostic test of pre-eclampsia

Resumen OBJETIVO: estructurar una pregunta clínica para conocer la utilidad de la prueba cualitativa de GPBB en sangre capilar de pacientes embarazadas, con la finalidad de establecer el diagnóstico de preeclampsia. MATERIALES Y MÉTODOS: estudio ambispectivo efectuado con base en las respuestas a la pregunta clínica estructurada: ¿cuál es la validez diagnóstica de la prueba cualitativa de la isoenzima BB de la fosforilasa de glucógeno (GPBB) en sangre capilar para preeclampsia? se buscaron las fuentes primarias en PubMed, mediante las palabras clave (MeSH): "Glycogen phosphorylase isoenzyme BB AND Pregnancy" y "Glycogen phosphorylase isoenzyme BB AND Pre-eclampsia". Se seleccionaron los artículos más relevantes, se les asignó nivel de evidencia, se investigó si la muestra y metodología fueron iguales, comparables o diferentes de la prueba cualitativa en sangre capilar, y se analizaron sus resultados con la finalidad de establecer el diagnóstico clínico de preeclampsia. RESULTADOS: no se encontraron estudios de la determinación cualitativa de GPBB en sangre capilar. En tres ensayos de casos y controles (nivel de evidencia 4) se compararon las concentraciones de GPBB en suero mediante ELISA y se encontraron cifras elevadas al momento de establecer el diagnóstico clínico; sin embargo, se consideró como un rasgo fenotípico de preeclampsia clínica, pero no como una prueba diagnóstica. CONCLUSIONES: no existe suficiente evidencia médica que respalde la utilidad de la determinación cualitativa de GPBB en sangre capilar de pacientes embarazadas para establecer el diagnóstico de preeclampsia; por lo tanto, no se sustenta su aplicación en ningún escenario clínico.

Abstract OBJECTIVE: To establish if the clinical use of the test for the diagnosis of pre-eclampsia is scientifically supported by evidence-based medicine. MATERIALS AND METHODS: Ambispective study based on the responses to the PICO clinical question was constructed, then primary sources were searched in PubMed by the strategies Glycogen phosphorylase isoenzyme BB AND Pregnancy, and Glycogen phosphorylase isoenzyme BB AND pre-eclampsia, the relevant ones were selected, with allocation of level of evidence, determining if samples and methodology were similar, comparable or different to the capillary blood test, and results were analized under diagnosis clinical intention. RESULTS: No studies were found on qualitative GPBB detection in capillary blood. Three case-control studies (evidence level 4) compared GPBB maternal serum levels determined by ELISA, and described an elevation of GPBB at clinical diagnosis, rather as a phenotypical feature of clinical Pre-eclampsia, but not a diagnostic test. CONCLUSIONS: There is no evidence at all to offer the qualitative determination of GPBB in capillary blood of pregnant women; its clinical use is not supported whatsoever.

La retina, una ventana al bagaje cardiovascular / The retina, a window to the cardiovascular baggage

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Estrogen promotes the brain metastatic colonization of triple negative breast cancer cells via an astrocyte-mediated paracrine mechanism.

Brain metastases (BM) are a devastating consequence of breast cancer. BM occur more frequently in patients with estrogen receptor-negative (ER-) breast cancer subtypes; HER2 overexpressing (HER2+) tumors and triple-negative (TN) (ER-, progesterone receptor-negative (PR-) and normal HER2) tumors. Young age is an independent risk factor for the development of BM, thus we speculated that higher circulating estrogens in young, pre-menopausal women could exert paracrine effects through the highly estrogen-responsive brain microenvironment. Using a TN experimental metastases model, we demonstrate that ovariectomy decreased the frequency of magnetic resonance imaging-detectable lesions by 56% as compared with estrogen supplementation, and that the combination of ovariectomy and letrozole further reduced the frequency of large lesions to 14.4% of the estrogen control. Human BM expressed 4.2-48.4% ER+ stromal area, particularly ER+ astrocytes. In vitro, E2-treated astrocytes increased proliferation, migration and invasion of 231BR-EGFP cells in an ER-dependent manner. E2 upregulated epidermal growth factor receptor (EGFR) ligands Egf, Ereg and Tgfa mRNA and protein levels in astrocytes, and activated EGFR in brain metastatic cells. Co-culture of 231BR-EGFP cells with E2-treated astrocytes led to the upregulation of the metastatic mediator S100 Calcium-binding protein A4 (S100A4) (1.78-fold, P<0.05). Exogenous EGF increased S100A4 mRNA levels in 231BR-EGFP cells (1.40±0.02-fold, P<0.01 compared with vehicle control) and an EGFR/HER2 inhibitor blocked this effect, suggesting that S100A4 is a downstream effector of EGFR activation. Short hairpin RNA-mediated S100A4 silencing in 231BR-EGFP cells decreased their migration and invasion in response to E2-CM, abolished their increased proliferation in co-cultures with E2-treated astrocytes and decreased brain metastatic colonization. Thus, S100A4 is one effector of the paracrine action of E2 in brain metastatic cells. These studies provide a novel mechanism by which estrogens, acting through ER+ astrocytes in the brain microenvironment, can promote BM of TN breast cancers, and suggests existing endocrine agents may provide some clinical benefit towards reducing and managing BM.