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Many plant species, particularly legumes, protect themselves with saponins. Previously, a correlation was observed between levels of oleanolic acid-derived saponins, such as hederagenin-derived compounds, in the legume Medicago truncatula and caterpillar deterrence. Using concentrations that reflect the foliar levels of hederagenin-type saponins, the sapogenin hederagenin was not toxic to 4th instar caterpillars of the cabbage looper Trichoplusia ni nor did it act as a feeding deterrent. Female caterpillars consumed more diet than males, presumably to obtain the additional nutrients required for oogenesis, and are, thus, exposed to higher hederagenin levels. When fed the hederagenin diet, male caterpillars expressed genes encoding trypsin-like proteins (LOC113500509, LOC113501951, LOC113501953, LOC113501966, LOC113501965, LOC113499659, LOC113501950, LOC113501948, LOC113501957, LOC113501962, LOC113497819, LOC113501946, LOC113503910) as well as stress-responsive (LOC113503484, LOC113505107) proteins and cytochrome P450 6B2-like (LOC113493761) at higher levels than females. In comparison, female caterpillars expressed higher levels of cytochrome P450 6B7-like (LOC113492289). Bioinformatic tools predict that cytochrome P450s could catalyze the oxygenation of hederagenin which would increase the hydrophilicity of the compound. Expression of a Major Facilitator Subfamily (MFS) transporter (LOC113492899) showed a hederagenin dose-dependent increase in gene expression suggesting that this transporter may be involved in sapogenin efflux. These sex-related differences in feeding and detoxification should be taken into consideration in insecticide evaluations to minimize pesticide resistance.
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Mariposas Nocturnas , Ácido Oleanólico , Ácido Oleanólico/análogos & derivados , Saponinas , Transcriptoma , Animales , Femenino , Masculino , Saponinas/metabolismo , Saponinas/química , Ácido Oleanólico/metabolismo , Ácido Oleanólico/farmacología , Ácido Oleanólico/química , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/fisiología , Mariposas Nocturnas/genética , Transcriptoma/efectos de los fármacos , Larva/efectos de los fármacos , Larva/genética , Caracteres SexualesRESUMEN
This study investigated how youth attachment anxiety and avoidance are associated with informant discrepancies of intrafamilial aggression within families where youth have clinically significant mental health challenges (N = 510 youth-parent dyads). Using polynomial regressions, we tested whether youth attachment avoidance and anxiety moderated the absolute magnitude of the association between youth- and parent-reports of aggression toward each other. Furthermore, difference scores were computed to test whether youth attachment was associated with the direction of youths' reports of the frequency of aggression relative to parents (i.e., did youth under- or over-report). Dyads' reports of youth-to-parent aggression were more strongly related at high than low levels of attachment anxiety. Results also revealed that youth attachment anxiety was associated with youth over-reporting of youth-to-parent and parent-to-youth aggression (relative to parents), whereas attachment avoidance was associated with youth over-reporting parent-to-youth aggression (relative to parents). These findings highlight the importance of understanding the source of informant discrepancies in social-emotional development and family functioning.
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The gastrointestinal (GI) tract consists of a remarkable series of organs that spatially and temporally coordinate the vital process of digestion to extract key nutrients required to sustain our day-to-day functions. During development, it undergoes complex and highly specialized morphogenetic events to form functionally distinct organs. Its failure to develop properly leads to serious congenital diseases, which if left untreated are particularly devastating and often result in premature death. These GI diseases have been estimated to impact approximately 8-16 of every 10,000 newborns [1, 2]. Importantly, the clinical manifestations of these diseases are severe, with untreated cases having high mortality rates. While some disorders, such as Hirschsprung's disease, can be treated effectively with surgery, the efficacy of this management strategy is far lower for other diseases, such as necrotizing enterocolitis. Moreover, children often face complications from these surgical procedures, leading to secondary ailments. Consequently, a better understanding of gastrointestinal development is fundamental to the treatment and prevention of congenital GI maladies. This chapter will explore some of the most prevalent and biologically complex congenital diseases of the GI system, with emphasis on animal models that both elucidate their underlying causes and lay the essential groundwork for the advancement of translational medicine.
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Modelos Animales de Enfermedad , Enfermedades Gastrointestinales/congénito , Animales , Enterocolitis Necrotizante/congénito , Enfermedad de Hirschsprung , HumanosRESUMEN
In this work, the first synthesis of poly(amidoamine) (PAMAM) dendrimers whose branches are hybridized with peptide segments (DendriPeps) is reported. The intercalation of amino acids within the branches of PAMAMs provides supplementary internal functionalities to the coronal groups. Four DendriPep prototypes are synthesized with lysine or glutamic acid as "guest" amino acids, displaying, respectively, a primary amine or a carboxyl group, on generation (G)2 and G3 PAMAMs as host scaffolds. The precise control over the number, type, and topological placement of functional groups expands the functional behavior of DendriPeps beyond current PAMAM dendrimers toward new frontiers or colloids, drug delivery vectors, and catalysis.
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Dendrímeros/química , Péptidos/química , Andamios del Tejido/química , Aminoácidos/química , Dendrímeros/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Simulación de Dinámica Molecular , Estructura Molecular , Péptidos/metabolismoRESUMEN
Limiting oxygen permeation through plastic films is important for extending the shelf life of food and flexible electronic devices. Polyelectrolyte complex (PEC) thin films can be used to reduce small molecule diffusion through commodity plastic films. PEC thin films are frequently applied using layer-by-layer assembly, which often requires many processing cycles to deposit a film with desired thickness. An aqueous solution of poly(diallydimethylammonium chloride) and poly(acrylic acid) can be deposited in a single-step to quickly fabricate a high-oxygen barrier thin film. These films have an ionically bonded network that forms after polyelectrolyte deposition and exposure to buffer. Increasing buffer concentration and adding salt increases film cohesion and improves transparency by reducing surface roughness. When deposited onto a 178 µm poly(ethylene terephthalate) film, a â¼1.9 µm thick PEC coating imparts a 2 orders of magnitude reduction in oxygen transmission rate. Achieving this level of gas barrier with a single thin coating layer creates numerous opportunities for the protection of sensitive food, pharmaceuticals, and electronics.
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Adenomyosis is a common benign uterine condition and a frequent cause of pelvic pain in premenopausal women. Transvaginal US is now considered the primary imaging modality for the diagnosis of adenomyosis, and thus radiologists should be familiar with its sonographic appearance. US findings can be divided into three categories, which parallel the histology of adenomyosis: (a) ectopic endometrial glands and stroma, (b) muscular hyperplasia/hypertrophy, and (c) increased vascularity. Ectopic endometrial glands manifest as echogenic nodules and striations, radiating from the endometrium into the myometrium. When the glands contain fluid, myometrial cysts and fluid-filled striations may be visible at US. Muscular hyperplasia and hypertrophy cause focal or diffuse myometrial thickening and globular uterine enlargement, often with thin "venetian blind" shadows. The combination of these findings results in a heterogeneous myometrium, with blurring of the endometrial border. Adenomyosis increases uterine vascularity, depicted as a pattern of penetrating vessels at color Doppler US. Other US techniques that are helpful in the diagnosis of adenomyosis include obtaining cine clips and coronal reformatted images, both of which can survey the entire endometrial-myometrial border, and performing saline-infusion sonohysterography, during which ectopic glands frequently fill with either air or fluid. While most cases of adenomyosis develop spontaneously, there are specific inciting causes that include tamoxifen use, postendometrial ablation syndrome, and deep-infiltrating endometriosis. Mimics of adenomyosis include leiomyomas, uterine contractions, neoplasms, and vascular malformations. This article reviews the pathophysiology of adenomyosis and correlates it with the US findings, highlights specific causes of adenomyosis, and describes how to distinguish this common diagnosis from a variety of mimics. Online supplemental material is available for this article. ©RSNA, 2018.
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Adenomiosis/diagnóstico por imagen , Ultrasonografía/métodos , Adenomiosis/etiología , Adenomiosis/fisiopatología , Diagnóstico Diferencial , Femenino , Humanos , Leiomioma/diagnóstico por imagen , Neoplasias Uterinas/diagnóstico por imagenRESUMEN
The connections between the five facets of mindfulness, well-being, and mental health across the lifespan have traditionally been investigated using variable-centered approaches. Less research has investigated these relationships from a person-centered, profile-based approach. In this work, we aimed to identify the profiles of mindfulness in a Canadian lifespan sample (14 to 90 years of age) and investigate how these profiles compared on age, well-being, and mental health. An age- and gender-balanced sample of 1,600 participants completed a questionnaire that measured the five facets of mindfulness; life satisfaction; existential well-being; and anxiety, depression, and stress symptoms. A latent profile analysis was conducted. Five profiles based on the five-facet model of mindfulness were identified: high mindfulness, moderate mindfulness, low mindfulness, nonjudgmentally aware, and judgmentally observing. The 3-step approach to profile comparisons was used to assess age, mental health, and well-being differences across the profiles. Those in the high mindfulness and nonjudgmentally aware profiles were generally older, while the judgmentally observing profile contained younger individuals. Those in the high mindfulness and nonjudgmentally aware profiles reported the greatest mental health and well-being. Conversely, those in the low mindfulness and judgmentally observing profiles had worse mental health than the other profiles. The moderate mindfulness profile was situated between these profile groups on age, mental health, and well-being outcomes. This pattern of results has implications for mindfulness-based intervention research and practice to better account for heterogeneity in mindfulness and better support well-being across the lifespan.
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BACKGROUND: Integrated Pest Management (IPM) seeks to combine multiple management strategies for optimal pest control. One method that is successfully employed in IPM is the use of beneficial organisms. However, in severe circumstances when pest insects exceed threshold limits, insecticides may still need to be implemented. Thus, understanding the effects of insecticides on biocontrol agents, such as parasitoid wasps, is paramount to ensure sustainable agroecosystems. Sublethal effects of the bioinsecticide spinosyn, a mixture of the bacterial Saccharopolyspora spinosa (Mertz and Yao) fermentation products spinosyn A and D, on eggs of Trichoplusia ni (Hübner), a cruciferous crop pest, and its egg parasitoid Trichogramma brassicae (Bezdenko) was investigated. RESULTS: The LC50 for spinosyn A and D (dissolved in ethanol) on T. ni eggs is 54 ng mL-1. Transcriptomics on caterpillars (1st and 3rd instars) that hatched from eggs treated with sublethal concentrations of spinosyn identified the upregulation of several genes encoding proteins that may be involved in insecticide resistance including detoxification enzymes, such as cytochrome P450s, glutathione S-transferases and esterases. Sublethal T. ni egg treatments did not affect parasitoid emergence, however, there was a marked increase in the size of T. brassicae hind tibia and wings that emerged from spinosyn-treated eggs. CONCLUSIONS: For the caterpillar, treatment of eggs with sublethal concentrations of spinosyn may induce insecticide resistance mechanisms. For the parasitoids, their increased size when reared in spinosyn-treated eggs suggests that the emerged wasps may have higher performance. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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Insecticidas , Larva , Macrólidos , Mariposas Nocturnas , Óvulo , Avispas , Animales , Mariposas Nocturnas/parasitología , Mariposas Nocturnas/efectos de los fármacos , Avispas/efectos de los fármacos , Avispas/fisiología , Óvulo/efectos de los fármacos , Óvulo/parasitología , Insecticidas/farmacología , Macrólidos/farmacología , Larva/crecimiento & desarrollo , Larva/efectos de los fármacos , Control Biológico de VectoresRESUMEN
Background: Inflammation is a sequela of cardiovascular critical illness and a risk factor for mortality. Objectives: This study aimed to evaluate the association between white blood cell count (WBC) and mortality in a broad population of patients admitted to the cardiac intensive care unit (CICU). Methods: This retrospective cohort study included patients admitted to the Mayo Clinic CICU between 2007 and 2018. We analyzed WBC as a continuous variable and then categorized WBC as low (<4.0 × 103/mL), normal (≥4.0 to <11.0 × 103/mL), high (≥11.0 to <22.0 × 103/mL), or very high (≥22.0 × 103/mL). The association between WBC and in-hospital mortality was evaluated using multivariable logistic regression and random forest models. Results: We included 11,699 patients with a median age of 69.3 years (37.6% females). Median WBC was 9.6 (IQR: 7.4-12.7). Mortality was higher in the low (10.5%), high (12.0%), and very high (33.3%) WBC groups relative to the normal WBC group (5.3%). A rising WBC was incrementally associated with higher in-hospital mortality after adjustment (AICc adjusted OR: 1.03 [95% CI: 1.02-1.04] per 1 × 103 increase in WBC). After adjustment, only the high (AICc adjusted OR: 1.37 [95% CI: 1.15-1.64]) and very high (AICc adjusted OR: 1.99 [1.47-2.71]) WBC groups remained associated with increased risk of in-hospital mortality. Conclusions: Leukocytosis is associated with an increased mortality risk in a diverse cohort of CICU patients. This readily available marker of systemic inflammation may be useful for risk stratification within the increasingly complex CICU patient population.
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Tear film stability decreases with age however the cause(s) of the instability are speculative. Perhaps the more saturated meibum from infants may contribute to tear film stability. The meibum lipid phase transition temperature and lipid hydrocarbon chain order at physiological temperature (33 °C) decrease with increasing age. It is reasonable that stronger lipid-lipid interactions could stabilize the tear film since these interactions must be broken for tear break up to occur. In this study, meibum from a pool of adult donors was saturated catalytically. The influence of saturation on meibum hydrocarbon chain order was determined by infrared spectroscopy. Meibum is in an anhydrous state in the meibomian glands and on the surface of the eyelid. The influence of saturation on the surface properties of meibum was determined using Langmuir trough technology. Saturation of native human meibum did not change the minimum or maximum values of hydrocarbon chain order so at temperatures far above or below the phase transition of human meibum, saturation does not play a role in ordering or disordering the lipid hydrocarbon chains. Saturation did increase the phase transition temperature in human meibum by over 20 °C, a relatively high amount. Surface pressure-area studies showing the late take off and higher maximum surface pressure of saturated meibum compared to native meibum suggest that the saturated meibum film is quite molecularly ordered (stiff molecular arrangement) and elastic (molecules are able to rearrange during compression and expansion) compared with native meibum films which are more fluid agreeing with the infrared spectroscopic results of this study. In saturated meibum, the formation of compacted ordered islands of lipids above the surfactant layer would be expected to decrease the rate of evaporation compared to fluid and more loosely packed native meibum. Higher surface pressure observed with films of saturated meibum compared to native meibum suggests greater film stability especially under the high shear stress of a blink.
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Lípidos/análisis , Glándulas Tarsales/química , Lágrimas/química , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Espectrofotometría Infrarroja , Propiedades de Superficie , TemperaturaRESUMEN
Recent NMR studies suggest that unsaturation may contribute to tear film instability in adults and loss of cholesteryl esters and squalene could reduce tear film stability in adults with meibomian gland dysfunction. The proton resonances were tentatively assigned in those studies. In this current investigation, meibum from seven infants and children, one adult and a pool of adult meibum have been analyzed using an NMR spectrometer with greater sensitivity and spectral resolution. The goals of this work are to confirm/correct the previous assignments and to determine possible age-related changes in composition. The initial resonance assignments were confirmed using heteronuclear single quantum correlation spectroscopy. Because there were no significant interferences in the spectral region corresponding to the resonances for cholesteryl and wax esters, the areas of these resonances were used to calculate their molar ratios. We calculated a wax ester:cholesteryl ester molar ratio of 1:0.57 ± 0.05 for all our meibum samples and there were no age-related differences. At lower film thicknesses, the rate of evaporation measured in vitro was lower for wax esters mixed with a long chain cholesteryl ester compared to wax esters alone. However, the film thicknesses tested were non-physiological. Longer chain cholesteryl esters increase the interactions between hydrocarbon chains. Hydrocarbon chains were more saturated in meibum from infants and children compared to adults. Unsaturation may contribute to tear film instability in adults. Loss of cholesteryl ester and squalene could destabilize tear film in adults with meibomian gland dysfunction.
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Ésteres del Colesterol/análisis , Glándulas Tarsales/química , Resonancia Magnética Nuclear Biomolecular , Ceras/análisis , Adolescente , Adulto , Anciano , Envejecimiento/fisiología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Espectroscopía Infrarroja por Transformada de Fourier , Lágrimas/químicaRESUMEN
ABSTRACT: Objective: To identify and describe characteristics of patients with sepsis who could be treated with minimally invasive sepsis (MIS) approach without intensive care unit (ICU) admission and to develop a prediction model to select candidates for MIS approach. Methods: A secondary analysis of the electronic database of patients with sepsis at Mayo Clinic, Rochester, MN. Candidates for the MIS approach were adults with septic shock and less than 48 hours of ICU stay, who did not require advanced respiratory support and were alive at hospital discharge. Comparison group consisted of septic shock patients with an ICU stay of more than 48 hours without advanced respiratory support at the time of ICU admission. Results: Of 1795 medical ICU admissions, 106 patients (6%) met MIS approach criteria. Predictive variables (age >65 years, oxygen flow >4 L/min, temperature <37°C, creatinine >1.6 mg/dL, lactate >3 mmol/L, white blood cells >15 × 10 9 /L, heart rate >100 beats/min, and respiration rate >25 breaths/min) selected through logistic regression were translated into an 8-point score. Model discrimination yielded the area under the receiver operating characteristic curve of 79% and was well fitted (Hosmer-Lemeshow P = 0.94) and calibrated. The MIS score cutoff of 3 resulted in a model odds ratio of 0.15 (95% confidence interval, 0.08-0.28) and a negative predictive value of 91% (95% confidence interval, 88.69-92.92). Conclusions: This study identifies a subset of low-risk septic shock patients who can potentially be managed outside the ICU. Once validated in an independent, prospective sample our prediction model can be used to identify candidates for MIS approach.
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Sepsis , Choque Séptico , Adulto , Humanos , Anciano , Estudios Prospectivos , Estudios Retrospectivos , Unidades de Cuidados Intensivos , Organización Mundial de la Salud , Pronóstico , Curva ROCRESUMEN
Epithelial-mesenchymal signaling in the gastrointestinal system is vital in establishing regional identity during organogenesis and maintaining adult stem cell homeostasis. Although recent work has demonstrated that Wnt ligands expressed by mesenchymal cells are required during gastrointestinal development and stem cell homeostasis, epigenetic mechanisms driving spatiotemporal control of crosstalk remain unknown. Here, we demonstrate that gastrointestinal mesenchymal cells control epithelial fate and function through Polycomb Repressive Complex 2-mediated chromatin bivalency. We find that while key lineage-determining genes possess tissue-specific chromatin accessibility, Polycomb Repressive Complex 2 controls Wnt expression in mesenchymal cells without altering accessibility. We show that reduction of mesenchymal Wnt secretion rescues gastrointestinal fate and proliferation defects caused by Polycomb Repressive Complex 2 loss. We demonstrate that mesenchymal Polycomb Repressive Complex 2 also regulates niche signals to maintain stem cell function in the adult intestine. Our results highlight a broadly permissive chromatin architecture underlying regionalization in mesenchymal cells, then demonstrate further how chromatin architecture in niches can influence the fate and function of neighboring cells.
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Tracto Gastrointestinal , Intestinos , Tracto Gastrointestinal/metabolismo , Complejo Represivo Polycomb 2/metabolismo , Cromatina/genética , Epigénesis Genética , Diferenciación Celular/genéticaRESUMEN
Little is known about endogenous estrogen receptor ß (ERß) gene targets in human breast cancer. We reported that estradiol (E(2)) induces nuclear respiratory factor-1 (NRF-1) transcription through ERα in MCF-7 breast cancer cells. Here we report that 4-hydroxytamoxifen (4-OHT), with an EC(50) of ~1.7 nM, increases NRF-1 expression by recruiting ERß, cJun, cFos, CBP, and RNA polymerase II to and dismissing NCoR from the NRF1 promoter. Promoter deletion and transient transfection studies showed that the estrogen response element (ERE) is essential and that an adjacent AP-1 site contributes to maximal 4-OHT-induced NRF-1 transcription. siRNA knockdown of ERß revealed that ERß inhibits basal NRF-1 expression and is required for 4-OHT-induced NRF-1 transcription. An AP-1 inhibitor blocked 4-OHT-induced NRF-1 expression. The 4-OHT-induced increase in NRF-1 resulted in increased transcription of NRF-1 target CAPNS1 but not CYC1, CYC2, or TFAM despite increased NRF-1 coactivator PGC-1α protein. The absence of TFAM induction corresponds to a lack of Akt-dependent phosphorylation of NRF-1 with 4-OHT treatment. Overexpression of NRF-1 inhibited 4-OHT-induced apoptosis and siRNA knockdown of NRF-1 increased apoptosis, indicating an antiapoptotic role for NRF-1. Overall, NRF-1 expression and activity is regulated by 4-OHT via endogenous ERß in MCF-7 cells.
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Receptor beta de Estrógeno/metabolismo , Factor Nuclear 1 de Respiración/genética , Tamoxifeno/análogos & derivados , Factor de Transcripción AP-1/metabolismo , Apoptosis/efectos de los fármacos , Sitios de Unión , Línea Celular Tumoral , Receptor alfa de Estrógeno/fisiología , Humanos , Regiones Promotoras Genéticas/efectos de los fármacos , Regiones Promotoras Genéticas/fisiología , Retinoides/farmacología , Transducción de Señal , Tamoxifeno/farmacología , Factor de Transcripción AP-1/antagonistas & inhibidores , Transcripción Genética/efectos de los fármacosRESUMEN
Cesarean delivery is a commonly performed operation and accounts for nearly one-third of all births in the United States. Although it is a safe procedure, cesarean delivery has a variety of acute and chronic complications that prompt imaging with ultrasonography (US), computed tomography, and magnetic resonance imaging. Acute complications include hematomas in specific locations that are unique to the procedure, as well as a variety of infections. A bladder flap hematoma occurs in the space between the bladder and the lower uterine segment, whereas a subfascial hematoma is an extraperitoneal collection located in the prevesical space posterior to the rectus muscles and anterior to the peritoneum. Puerperal infections after cesarean delivery include abscesses, wound infections and dehiscence, uterine dehiscence and rupture, and pelvic thrombophlebitis. The prevalence of chronic complications related to the healed cesarean delivery scar is unknown, but the scar may result in technical limitations for pelvic US due to the adhesions between the anterior lower uterine segment and the anterior abdominal wall. The cesarean delivery scar also leaves the patient susceptible to several unique diagnoses. A cesarean scar "niche" is a tethering of the endometrium that can serve as a reservoir for intermenstrual blood and fluid. Intrauterine devices can be malpositioned in the cesarean delivery scar, and endometrial implants can develop in the abdominal wall years after surgery. These patients are also at increased risk for implantation abnormalities including cesarean scar ectopic pregnancy, retained products of conception, and placenta accreta. Familiarity with the normal postoperative findings following cesarean delivery is necessary to recognize acute and chronic complications, which are being encountered with increasing frequency.
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Cesárea , Diagnóstico por Imagen , Complicaciones del Trabajo de Parto/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Trastornos Puerperales/diagnóstico , Adulto , Medios de Contraste , Femenino , Humanos , EmbarazoRESUMEN
The incidence of cervical cancer has decreased in recent years due to widespread vaccination and routine screenings. It can be treated successfully, and the prognosis is also excellent if detected early. However, the 5-year survival rate for patients with stage IV cervical cancer is only 17% even with aggressive systemic chemotherapy. With the Food and Drug Administration (FDA)'s approval of immunotherapy, the prognosis has improved. We present a patient with stage IV cervical cancer who could not tolerate platinum-based chemotherapy and bevacizumab, so she was started on an immune checkpoint inhibitor, as her tumor was 100% programmed cell death ligand-1 (PD-L1) positive. She survived more than 2 years since the diagnosis of stage IV cervical cancer without any significant side effects. Based on our patient's response, the use of immune checkpoint inhibitors as a single agent needs further research and probably can be considered in patients with stage 4 cervical cancer who cannot tolerate standard chemotherapy.
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Background: Delirium is common in patients with severe coronavirus disease-19 (COVID-19). The purpose of our study was to determine whether severe COVID-19 is an independent risk factor for the development of delirium in patients treated in the intensive care unit (ICU). Methods: This prospective observational cohort study involved 162 critically ill patients admitted to a multidisciplinary ICU during 2019 and 2020. A validated screening tool was used to diagnose delirium. Multiple delirium risk factors were collected daily including clinical characteristics, hospital course, lab values, vital signs, surgical exposure, drug exposure, and COVID-19 characteristics. After univariate analysis, a multivariate logistic regression analysis was performed to determine independent risk factors associated with the development of delirium. Results: In our study population, 50 (31%) patients developed delirium. A total of 39 (24.1%) tested positive for COVID-19. Initial analysis showed COVID-19 to be more prevalent in those patients that developed delirium (40% vs. 17%; P = 0.003). Multivariate analysis showed opioid use (odds ratio [OR]: 24 [95% confidence intervals (CI): 16-27]; P ≤ 0.001), benzodiazepine use (OR: 23 [95% CI: 16-63] P = 0.001), and estimated mortality based on acute physiology and chronic health evaluation IV score (OR: 1.04 [95% CI: 1.01-1.07] P = 0.002) to be independently associated with delirium development. COVID-19 (OR: 1.44 [95% CI: 0.13-10.6]; P = 0.7) was not found to be associated with delirium. Conclusion: Delirium is prevalent in critically ill patients admitted to the ICU, including those with COVID-19. However, after adjustment for important covariates, we found in this cohort that COVID-19 was not an independent risk factor for delirium.
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BACKGROUND: Neuroinflammation causing disruption of the blood-brain barrier and immune cell extravasation into the brain parenchyma may cause delirium; however, knowledge of the exact pathophysiologic mechanism remains incomplete. The purpose of our study was to determine whether cytokine profiles differ depending on whether delirium occurs in the setting of sepsis, coronavirus disease 2019 (COVID-19), or recent surgery. METHODS: This prospective observational cohort study involved 119 critically ill patients admitted to a multidisciplinary intensive care unit (ICU) during 2019 and 2020. Delirium was identified using the validated confusion assessment method for the ICU. Multiple delirium risk factors were collected daily including clinical characteristics, hospital course, lab values, vital signs, surgical exposure, drug exposure, and COVID-19 characteristics. Serums samples were collected within 12 hours of ICU admission and cytokine levels were measured. RESULTS: The following proinflammatory cytokines were elevated in our delirium population: tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, C-C motif ligand (CCL) 2, CCL3, C-X-C motif chemokine ligand (CXCL)1, CXCL10, IL-8, IL-1 receptor antagonist, and IL-10. Analysis of relative cytokine levels in those patients that developed delirium in the setting of sepsis, COVID-19, and recent surgery showed elevations of CCL2, CXCL10, and TNF-α in both the sepsis and COVID-19 group in comparison to the postsurgical population. In the postsurgical group, granulocyte colony-stimulating factor was elevated and CXCL10 was decreased relative to the opposing groups. CONCLUSIONS: We identify several cytokines and precipitating factors known to be associated with delirium. However, our study suggests that the cytokine profile associated with delirium is variable and contingent upon delirium precipitating factors.