Small GTPases of the Ras subfamily are best known for their role as proto-oncoproteins, while their function during microbial infection has remained elusive. Here, we show that Legionella pneumophila hijacks the small GTPase NRas to the Legionella-containing vacuole (LCV) surface. A CRISPR interference screen identifies a single L. pneumophila effector, DenR (Lpg1909), required for this process. Recruitment is specific for NRas, while its homologs KRas and HRas are excluded from LCVs. The C-terminal hypervariable tail of NRas is sufficient for recruitment, and interference with either NRas farnesylation or S-acylation sites abrogates recruitment. Intriguingly, we detect markers of active NRas signaling on the LCV, suggesting it acts as a signaling platform. Subsequent phosphoproteomics analyses show that DenR rewires the host NRas signaling landscape, including dampening of the canonical mitogen-activated protein kinase pathway. These results provide evidence for L. pneumophila targeting NRas and suggest a link between NRas GTPase signaling and microbial infection.
Bacterial Proteins , GTP Phosphohydrolases , Legionella pneumophila , MAP Kinase Signaling System , Membrane Proteins , Legionella pneumophila/metabolism , Legionella pneumophila/pathogenicity , Humans , Membrane Proteins/metabolism , Membrane Proteins/genetics , GTP Phosphohydrolases/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Down-Regulation , HEK293 Cells , Legionnaires' Disease/microbiology , Legionnaires' Disease/metabolism , Vacuoles/metabolism , Proto-Oncogene Proteins p21(ras)/metabolism , Proto-Oncogene Proteins p21(ras)/genetics
OBJECTIVES: Data are scarce regarding the prevalence and predictors of perinatal mood and anxiety disorders (PMADs) among Black women. The purpose of this study was to examine the prevalence and predictors of symptoms of PMADS among Black women. METHODS: Black women completed a paper survey between August 2019 and October 2019. Binomial logistic regression was employed to examine predictors of PMAD symptoms. RESULTS: The prevalence of symptoms of PMADs was 56%. A higher proportion of women with PMADs had experienced depression (16% vs. 32%, p = 0.006); physical (18% vs. 31%, p = 0.030), emotional (35% vs. 61%, p = 0.000), or sexual abuse (12% vs. 29%, p = 0.002); and symptoms of depression or anxiety before pregnancy (18% vs. 46%, p = 0.000). After adjusting for socio-demographics in multivariate analysis, experiencing symptoms of depression or anxiety before pregnancy (adjusted odds ratio [aOR] = 3.445, p = 0.001) was positively associated with experiencing symptoms of PMADs, whereas higher levels of self-esteem (aOR = 0.837, p = 0.000) were negatively associated with experiencing symptoms of perinatal mood and anxiety disorders. CONCLUSIONS FOR PRACTICE: The prevalence of PMAD symptoms among this sample of Black women was alarmingly high. Women who experienced PMADs were more likely to report adverse childhood experiences (e.g., physical, emotional, and/or sexual abuse). By understanding the prevalence of PMADs and the factors associated with these disorders, healthcare professionals can improve diagnosis and treatment rates among this understudied and underserved population.
Anxiety Disorders , Anxiety , Anxiety/epidemiology , Anxiety/psychology , Anxiety Disorders/diagnosis , Anxiety Disorders/epidemiology , Anxiety Disorders/psychology , Depression/diagnosis , Depression/epidemiology , Depression/psychology , Female , Humans , Mood Disorders/diagnosis , Mood Disorders/epidemiology , Parturition , Pregnancy , Prevalence
BACKGROUND AND PURPOSE: A recent report suggested that a serious burn injury was due to the presence of the identification (ID) wristband. As such, in lieu of removing or padding hospital ID wristbands in all patients prior to magnetic resonance imaging (MRI), testing may be performed to characterize risks for ID wristbands. Therefore, the purpose of this investigation was to evaluate the magnetic field interactions, heating and artifacts at 3 T for a hospital ID wristband. MATERIALS AND METHODS: Standardized test methods were used to evaluate magnetic field interactions, MRI-related heating, and artifacts at 3 T for a hospital ID wristband. RESULTS: There were no magnetic field interactions. MRI-related heating evaluated at a relatively high, MR system-reported, whole body-averaged specific absorption rate (2.9 W/kg) did not increase above the background level. The artifacts related to the ink used for printing were "small" for one toner and "large" for the other in relation to the dimensions of the printing. CONCLUSIONS: Based on the tests performed, this particular hospital ID wristband is considered MR safe and will not pose a hazard to a patient undergoing an MRI examination. Importantly, it is not necessary to remove this item for a patient referred for MRI.
Burns/prevention & control , Equipment Failure , Magnetic Resonance Imaging/adverse effects , Magnetic Resonance Imaging/instrumentation , Patient Identification Systems , Burns/etiology , Equipment Failure Analysis/methods , Hot Temperature , Humans , Wrist
OBJECTIVE: A newly developed CSF shunt valve that incorporates a magnetically adjustable mechanism designed to resist unintended setting changes was evaluated for problems during 3-T MRI. MATERIALS AND METHODS: Standardized protocols were used to assess magnetic field interactions, MRI-related heating, artifacts, and functional changes related to multiple exposures and various MRI conditions in nine different samples at 3 T. RESULTS: The magnetic field interactions were not excessive. MRI-related heating, which was studied at a relatively high, MRI system-reported whole body-averaged specific absorption rate (2.9 W/kg), was at a level that should not pose a hazard to a patient. Although artifacts were large in relation to the dimensions of this programmable CSF shunt valve, the results were consistent with similar devices containing permanent magnets. Multiple exposures and various MRI conditions at 3 T did not damage or affect the functional aspects of the devices, and no unintentional changes to the valve setting were observed. CONCLUSION: In consideration of the test results, this new programmable CSF shunt valve is not adversely affected by the 3-T MRI environment and is acceptable for a patient undergoing MRI at 3 T or less when specific guidelines are followed, including verifying the valve setting according to manufacturer recommendations immediately after the MRI procedure.
Burns, Electric/etiology , Burns, Electric/prevention & control , Cerebrospinal Fluid Shunts/adverse effects , Magnetic Resonance Imaging/adverse effects , Magnetic Resonance Imaging/instrumentation , Equipment Design , Equipment Failure Analysis , Humans
La enfermedad hipertensiva aguda del embarazo (EHAE) es un síndrome vasoespástico probablemente debido a un factor placentario. Una vez establecido el síndrome hipertensivo, el flujo uteroplacentario se reduce y el flujo intervelloso disminuye. Desde la semana 18-24 antes que la EHAE sea clínicamente manifiesta, se pueden encontrar cambios en relación a la velocidad del flujo placentario con técnicas del Doppler color. Las teorías placentarias sobre el origen de la EHAE se centran en el efecto de la hipoxia sobre el trofoblasto del primer trimestre. Las consecuencias de la isquemia placentaria son evidentes y están ubicadas en el lecho uteroplacentario y guardan una estrecha relación con los períodos de invasión del trofoblasto a las arterias espirales durante las semanas decimocuarta y vigésima. Al finalizar la invasión por el trofoblasto éstas son convertidas en un sistema de alta capacitancia al flujo sanguíneo; el defecto observado en la EHAE es la deficiente invasión del trofoblasto a las arterias maternas. La fisiopatología del daño endotelial probablemente se orgina en la disminución del flujo uteroplacentario, manifestándose en la disminución en la producción de prostaglandinas, la activación de la cascada de la coagulación, la agregación de fibrina a la pared endotelial y el incremento de la permeabilidad vascular. El futuro en las pruebas de laboratorio para pacientes con EHAE será el que se centre en desarrollar pruebas que ayuden al clínico a predecir la aparición de este síndrome. Avances recientes se han realizado en este campo. Las concentraciones de fibronectina se elevan 3-4 semanas antes de la manifestación clínica de la EHAE y en los casos que desarrollan EHAE grave estas concentraciones disminuyen de manera anormal. La hipocalciuria se ha descrito como un predictor temprano en el desarrollo de la EHAE. De esta misma forma el ácido úrico, la betatromboglobulina, la prolactina y el péptido atrial natriurético estan probando tener un valor de predicción y de selección para el estudio de EGAE. Dentro de las nuevas pruebas predictivas la gonadotropina coriónica humana se han vinculado como un factor secretado por la placenta en respuesta a la falta de invasión trofoblástica durante el segundo trimestre y como un marcador temprano de desarrollo de EHAE y aunque los resultados son prometedores, éstos deberán ser sometidos a mayores pruebas de confirmación clínica
Humans , Pregnancy , Uric Acid , beta-Thromboglobulin , Chorionic Gonadotropin , Eclampsia , Hypoxia , Pre-Eclampsia , Prolactin , Thrombocytopenia
