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The occurrence of superconductivity in proximity to various strongly correlated phases of matter has drawn extensive focus on their normal state properties, to develop an understanding of the state from which superconductivity emerges1-4. The recent finding of superconductivity in layered nickelates raises similar interests5-8. However, transport measurements of doped infinite-layer nickelate thin films have been hampered by materials limitations of these metastable compounds: in particular, a high density of extended defects9-11. Here, by moving to a substrate (LaAlO3)0.3(Sr2TaAlO6)0.7 that better stabilizes the growth and reduction conditions, we can synthesize the doping series of Nd1-xSrxNiO2 essentially free from extended defects. In their absence, the normal state resistivity shows a low-temperature upturn in the underdoped regime, linear behaviour near optimal doping and quadratic temperature dependence for overdoping. This is phenomenologically similar to the copper oxides2,12 despite key distinctions-namely, the absence of an insulating parent compound5,6,9,10, multiband electronic structure13,14 and a Mott-Hubbard orbital alignment rather than the charge-transfer insulator of the copper oxides15,16. We further observe an enhancement of superconductivity, both in terms of transition temperature and range of doping. These results indicate a convergence in the electronic properties of both superconducting families as the scale of disorder in the nickelates is reduced.
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Interaural time differences (ITDs) are a major cue for sound localization and change with increasing head size. Since the barn owl's head width more than doubles in the month after hatching, we hypothesized that the development of their ITD detection circuit might be modified by experience. To test this, we raised owls with unilateral ear inserts that delayed and attenuated the acoustic signal, and then measured the ITD representation in the brainstem nucleus laminaris (NL) when they were adults. The ITD circuit is composed of delay line inputs to coincidence detectors, and we predicted that plastic changes would lead to shorter delays in the axons from the manipulated ear, and complementary shifts in ITD representation on the two sides. In owls that received ear inserts starting around P14, the maps of ITD shifted in the predicted direction, but only on the ipsilateral side, and only in those tonotopic regions that had not experienced auditory stimulation prior to insertion. The contralateral map did not change. Thus, experience-dependent plasticity of the ITD circuit occurs in NL, and our data suggest that ipsilateral and contralateral delays are independently regulated. As a result, altered auditory input during development leads to long-lasting changes in the representation of ITD.Significance Statement The early life of barn owls is marked by increasing sensitivity to sound, and by increasing ITDs. Their prolonged post-hatch development allowed us to examine the role of altered auditory experience in the development of ITD detection circuits. We raised owls with a unilateral ear insert and found that their maps of ITD were altered by experience, but only in those tonotopic regions ipsilateral to the occluded ear that had not experienced auditory stimulation prior to insertion. This experience-induced plasticity allows the sound localization circuits to be customized to individual characteristics, such as the size of the head, and potentially to compensate for imbalanced hearing sensitivities between the left and right ears.
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Localización de Sonidos , Estrigiformes , Animales , Localización de Sonidos/fisiología , Audición , Tronco Encefálico/fisiología , Estimulación Acústica , Vías Auditivas/fisiologíaRESUMEN
Exposure to volatile organic compounds (VOCs) such as benzene, toluene, ethylbenzene, xylene, and formaldehyde from long-distance buses has been reported to adversely affect human health. This study investigates the concentrations of these five VOCs and evaluates their health risks to drivers and passengers on board. Ten trips from Taipei to Taichung were performed during the warm and cold seasons of 2021-2022. Two locations inside the bus were established to collect air samples by a 6-liter canister for drivers and passengers. Exposure concentrations of benzene, toluene, ethylbenzene, and xylene were analyzed via gas chromatography with a flame ionization detector and the formaldehyde concentration was monitored using a formaldehyde meter. Subsequently, a Monte Carlo simulation was conducted to evaluate the carcinogenic and non-carcinogenic risks of the five VOCs. Formaldehyde emerged as the highest detected compound (9.06 ± 3.77 µg/m3), followed by toluene (median: 6.11 µg/m3; range: 3.86-14.69 µg/m3). In particular, formaldehyde was identified to have the significantly higher concentration during non-rush hours (10.67 ± 3.21 µg/m3) than that during rush hours (7.45 ± 3.41 µg/m3) and during the warm season (10.71 ± 2.97 µg/m3) compared with that during the cold season (7.41 ± 4.26 µg/m3). Regarding non-carcinogenic risks to drivers and passengers, the chronic hazard indices for these five VOCs were under 1 to indicate an acceptable risk. In terms of carcinogenic risk, the median risks of benzene and formaldehyde for drivers were 2.88 × 10-6 (95% confidence interval [CI]: 2.11 × 10-6 - 5.13 × 10-6) and 1.91 × 10-6 (95% CI: 4.54 × 10-7 - 3.44 × 10-6), respectively. In contrast, the median carcinogenic risks of benzene and formaldehyde for passengers were less than 1 × 10-6 to present an acceptable risk. This study suggests that benzene and formaldehyde may present carcinogenic risks for drivers. Moreover, the non-carcinogenic risk for drivers and passengers is deemed acceptable. We recommended that the ventilation frequency be increased to mitigate exposure to VOCs in long-distance buses.
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Contaminantes Atmosféricos , Compuestos Orgánicos Volátiles , Compuestos Orgánicos Volátiles/análisis , Humanos , Medición de Riesgo , Contaminantes Atmosféricos/análisis , Vehículos a Motor , Taiwán , Exposición a Riesgos Ambientales/análisis , Formaldehído/análisis , Emisiones de Vehículos/análisis , Exposición Profesional/análisis , Monitoreo del AmbienteRESUMEN
OBJECTIVE: This study aimed to compare sleep quality at 1 year postpartum following a hypertensive disorder of pregnancy (HDP) among individuals with persistent postpartum hypertension (HTN) compared with those with normal blood pressures (BPs). STUDY DESIGN: We combined data from the Heart Health 4 New Moms pilot randomized trial (n = 118) and the Pathways prospective cohort study (n = 36). Individuals with a singleton pregnancy complicated by gestational HTN or preeclampsia underwent a research study visit at a mean 48.7 ± 9.5 weeks postpartum with standardized BP measurement and assessment of subjective sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Persistent postpartum HTN was defined as Stage 1 HTN or greater (mean systolic BP ≥ 130 mm Hg or mean diastolic BP ≥ 80 mm Hg over three measurements at rest) or requiring antihypertensive medication. Statistical analysis was performed using univariate and multivariable logistic regression analyses. RESULTS: Of 154 individuals with an HDP included in the analysis, 84 (55%) were normotensive at 1 year postpartum and 70 (45%) had persistent postpartum HTN. Individuals with persistent postpartum HTN were more likely to be older, self-identify as Black race, have higher prepregnancy and 1-year postpartum body mass index (BMI), be multiparous, and deliver at an earlier gestational age. The mean global PSQI score was 8.7 ± 3.7, with 81% reporting poor sleep (PSQI > 5), and scores were higher among individuals who were persistently hypertensive (9.6 ± 3.5) compared with those who were normotensive at 1 year postpartum (7.9 ± 3.6), p < 0.01. Findings were unchanged in a multivariable model adjusting for age, self-reported race, prepregnancy BMI, and parity. CONCLUSION: Following an HDP, individuals reported poor sleep quality at 1 year postpartum. Individuals with persistent postpartum HTN reported lower sleep quality, suggesting that sleep behavior may be a target for intervention to improve maternal cardiovascular health following an HDP. KEY POINTS: · After an HDP, poor sleep quality was common at 1 year postpartum.. · Those with persistent postpartum HTN reported worse sleep quality at 1 year postpartum.. · Sleep behavior may be a target for intervention to improve maternal cardiovascular health..
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Hipertensión Inducida en el Embarazo , Hipertensión , Periodo Posparto , Calidad del Sueño , Humanos , Femenino , Adulto , Embarazo , Estudios Prospectivos , Modelos Logísticos , Preeclampsia , Presión Sanguínea , Índice de Masa Corporal , Trastornos Puerperales , Adulto Joven , Proyectos PilotoRESUMEN
Despite serum progesterone being a widely accepted method for luteal phase support during embryo transfer cycles, debates persist regarding the optimal strategy for guiding clinical decisions on progesterone dosages to maximize reproductive outcomes. This retrospective study explored the utility of microRNA (miRNA) biomarkers in guiding personalized progesterone dosage adjustments for frozen embryo transfer (FET) cycles in 22 in vitro fertilization (IVF) patients undergoing hormone replacement therapy. Utilizing MIRA, an miRNA-based endometrial receptivity test, we analyzed patients' miRNA expression profiles before and after progesterone dosage adjustments to determine suitable dosages and assess endometrial status. Despite patients receiving identical progesterone dosages, variations in miRNA profiles were observed in the initial cycle, and all patients presented a displaced window of implantation. Following dosage adjustments based on their miRNA profiles, 91% of patients successfully transitioned their endometrium towards the receptive stages. However, two patients continued to exhibit persistent displaced receptivity despite the adjustments. Given the evident variation in endometrial status and serum progesterone levels among individuals, analyzing miRNA expression profiles may address the challenge of inter-personal variation in serum progesterone levels, to deliver more personalized dosage adjustments and facilitate personalized luteal phase support in IVF.
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MicroARNs , Progesterona , Femenino , Humanos , Fase Luteínica , Estudios Retrospectivos , MicroARNs/genética , Transferencia de Embrión , EndometrioRESUMEN
OBJECTIVE: The laryngeal force sensor (LFS) measures force during suspension microlaryngoscopy (SML) procedures, and has been previously shown to predict postoperative complications. Reproducibility of its measurements has not been described. STUDY DESIGN: Prospective cohort study. SETTING: Academic medical center. METHODS: 291 adult patients had force data collected from 2017 to 2021 during various SML procedures. 94 patients had passive LFS monitoring (surgeon blinded to intraoperative recordings) and 197 had active LFS monitoring (surgeon able to see LFS recordings). 27 of these patients had repeat procedures, with unique LFS metrics for each procedure. The 27 patients were divided into three groups. Group 1 had passive use for both procedures, group 2 had passive use for the first procedure and active use for the second, and group 3 had active use for both procedures. Force metrics from the two procedures were compared with a paired samples t-test. RESULTS: For airway dilation procedures and cancer resection procedures, average force variances were significantly lower with active versus passive use of the LFS. Group 1-no significant changes in maximum force (procedure 1 = 163.8 N, procedure 2 = 133.8 N, p = 0.324) or average force (procedure 1 = 93.6 N, procedure 2 = 78.3 N, p = 0.617). Group 2-maximum force dropped by 35 % between procedures 1 (219.2 N) and 2 (142.5 N), p = 0.013. Average force dropped by 42.5 % between procedures 1 (147.2 N) and 2 (84.6 N), p = 0.007. Group 3-no significant changes in maximum force (procedure 1 = 158.6 N, procedure 2 = 158.2 N, p = 0.986) or average force (procedure 1 = 94.2, procedure 2 = 81.8, p = 0.419). CONCLUSIONS: LFS measurements were reproducible for similar procedures in the same patient when the type of LFS monitoring was not a confounder.
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Laringe , Adulto , Humanos , Estudios Prospectivos , Reproducibilidad de los Resultados , Laringe/cirugía , Laringoscopía/métodos , Complicaciones Posoperatorias/cirugíaRESUMEN
The COVID-19 vaccines are highly effective in preventing COVID-19 illness; however, pregnant people were not included in the original COVID-19 vaccine trials, with resultant conflicting recommendations from health organizations regarding vaccinations for this high-risk population. Pregnant and lactating healthcare workers (HCWs), along with people planning a pregnancy, identified as "obstetric HCWs" in our study, were among the first to make decisions regarding vaccinating themselves against COVID-19. Given that HCWs are key sources of information and access to vaccinations, this study was conducted to understand the perceptions and knowledge of obstetric HCWs regarding the COVID-19 vaccine. An electronic survey to HCWs at a tertiary care institution in Pittsburgh, PA identified 83 obstetric HCWs, of which 65 (78.3%) received at least one dose of the either the Pfizer or Moderna COVID-19 vaccine, and 18 (21.7%) had not received any doses of vaccine. Pregnancy status influenced more people not to receive than to receive the vaccine. We found that both vaccinated and non-vaccinated obstetric HCWs had accurate knowledge regarding the COVID-19 vaccine. However, compared to non-vaccinated obstetric HCWs, vaccinated obstetric HCWs tended to endorse beliefs regarding herd immunity, believed they had a higher chance of acquiring COVID-19, and felt that the COVID-19 vaccine was safe for fetuses and people who were pregnant, lactating, breastfeeding, or planning a pregnancy. This study offers insight into obstetric individuals' perceptions and knowledge of the COVID-19 vaccine, and highlights areas where additional education and outreach may help obstetric individuals make informed decisions on receiving the COVID-19 vaccine.
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MicroRNAs (miRNAs) can regulate the expression of genes involved in the establishment of the window of implantation (WOI) in the endometrium. Recent studies indicated that cell-free miRNAs in uterine fluid and blood samples could act as alternative and non-invasive sample types for endometrial receptivity analysis. In this study, we attempt to systematically evaluate whether the expression levels of cell-free microRNAs in blood samples could be used as non-invasive biomarkers for assessing endometrial receptivity status. We profiled the miRNA expression levels of 111 blood samples using next-generation sequencing to establish a predictive model for the assessment of endometrial receptivity status. This model was validated with an independent dataset (n = 73). The overall accuracy is 95.9%. Specifically, we achieved accuracies of 95.9%, 95.9%, and 100.0% for the pre-receptive group, the receptive group, and the post-respective group, respectively. Additionally, we identified a set of differentially expressed miRNAs between different endometrial receptivity statuses using the following criteria: p-value < 0.05 and fold change greater than 1.5 or less than -1.5. In conclusion, the expression levels of cell-free miRNAs in blood samples can be utilized in a non-invasive manner to distinguish different endometrial receptivity statuses.
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MicroARN Circulante , MicroARNs , Femenino , Humanos , Implantación del Embrión/genética , Transferencia de Embrión , Endometrio , MicroARNs/genéticaRESUMEN
In the past 25 years, a number of efforts have been made toward the development of small molecule interleukin-6 (IL-6) signaling inhibitors, but none have been approved to date. Monosaccharides are a diverse class of bioactive compounds, but thus far have been unexplored as a scaffold for small molecule IL-6-signaling inhibitor design. Therefore, in this present communication, we combined a structure-based drug design approach with carbohydrate building blocks to design and synthesize novel IL-6-signaling inhibitors targeting glycoprotein 130 (gp130). Of this series of compounds, LS-TG-2P and LS-TF-3P were the top lead compounds, displaying IC50 values of 6.9 and 16 µM against SUM159 cell lines, respectively, while still retaining preferential activity against the IL-6-signaling pathway. The carbohydrate moiety was found to improve activity, as N-unsubstituted triazole analogues of these compounds were found to be less active in vitro compared to the leads themselves. Thus, LS-TG-2P and LS-TF-3P are promising scaffolds for further development and study as IL-6-signaling inhibitors.
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Antineoplásicos , Interleucina-6 , Antineoplásicos/farmacología , Carbohidratos/farmacología , Línea Celular Tumoral , Proliferación Celular , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Interleucina-6/metabolismo , Simulación del Acoplamiento Molecular , Estructura Molecular , Transducción de Señal , Relación Estructura-Actividad , HumanosRESUMEN
In this review, we discuss stool donor screening considerations to mitigate potential risks of pathogen transmission through fecal microbiota transplant (FMT) in solid organ transplant (SOT) recipients. SOT recipients have a higher risk for Clostridioides difficile infection (CDI) and are more likely to have severe CDI. FMT has been shown to be a valuable tool in the treatment of recurrent CDI (RCDI); however, guidelines for screening for opportunistic infections transmitted through FMT are underdeveloped. We review reported adverse effects of FMT as they pertain to an immunocompromised population and discuss the current understanding and recommendations for screening found in the literature while noting gaps in research. We conclude that while FMT is being performed in the SOT population, typically with positive results, there remain many unanswered questions which may have major safety implications and warrant further study.
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Infecciones por Clostridium , Trasplante de Microbiota Fecal , Trasplante de Órganos , Receptores de Trasplantes , Clostridioides difficile , Infecciones por Clostridium/etiología , Infecciones por Clostridium/prevención & control , Selección de Donante , Trasplante de Microbiota Fecal/métodos , Humanos , Trasplante de Órganos/efectos adversos , Recurrencia , Resultado del TratamientoRESUMEN
PURPOSE: Metastatic breast cancer (mBC) remains incurable and is associated with low survival rates. This study assessed the efficacy and safety of liposomal irinotecan in heavily pretreated patients with mBC, with or without active brain metastases (BM). METHODS: Following the dose escalation phase and determination of recommended phase 2 dose, the expansion phase of this phase I, open-label, non-randomized study, assigned adult women to cohorts based on mBC subtype: cohort 1, hormone receptor +/human epidermal growth factor receptor 2-; cohort 2, triple-negative breast cancer; or cohort 3, any mBC subtype with active BM. Patients received liposomal irinotecan 50 or 70 mg/m2 free base every 2 weeks. Here, we report secondary outcomes including best overall response (BOR), objective response rate (ORR), and treatment-emergent adverse events (TEAEs). RESULTS: For non-central nervous system (non-CNS) disease across all cohorts (intent-to-treat population, N = 29), the ORR was 34.5% (95% confidence interval: 17.94-54.33), with a BOR of partial response in 10 patients (34.5%), stable disease in five (17.2%), progressive disease in 10 (34.5%); four patients were unevaluable (13.8%). The ORR for the CNS cohort was 30.0% (95% confidence interval: 6.67-65.25) using modified Response Evaluation Criteria in Solid Tumors. Common grade 3 or higher TEAEs were diarrhea (27.6%), nausea (17.2%), fatigue (13.8%), asthenia (10.3%), and hypokalemia (10.3%). Serious treatment-related TEAEs were reported in six patients (20.7%). No treatment-related TEAEs resulted in death. CONCLUSIONS: Liposomal irinotecan monotherapy demonstrated antitumor activity in heavily pretreated patients with mBC, with or without BM. The observed safety profile was consistent with that in previous studies. CLINICAL TRIAL REGISTRATION: Trial registration ID NCT01770353.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Irinotecán , Tasa de Supervivencia , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/tratamiento farmacológicoRESUMEN
OBJECTIVE: This study aimed to examine the rates of intraamniotic infection between intrauterine pressure catheter with amnioinfusion and intrauterine pressure catheter alone. STUDY DESIGN: This was a retrospective cohort study of all women who had an intrauterine pressure catheter placement during labor at a tertiary referral hospital from January 2016 to June 2018. Outcomes were compared between women who had an intrauterine pressure catheter with amnioinfusion and intrauterine pressure catheter placement alone. The primary outcome was the rate of intraamniotic infection. Secondary outcomes included postpartum endometritis, postpartum hemorrhage (blood loss of ≥1,000 mL), quantitative blood loss (mL), and cesarean delivery. Multivariable logistic regression analysis was performed to calculate adjusted odds ratios (aOR) and 95% confidence interval (95% CI), controlling for age, race, body mass index, gestational age, and length of time of rupture of membranes. RESULTS: Of 1,268 women with an intrauterine pressure catheter, 298 (23.5%) also had an amnioinfusion. Women who had amnioinfusion through an intrauterine pressure catheter compared with those who had intrauterine pressure catheter alone had similar rates of intraamniotic infection (5.4 vs. 8.0%, crude p = 0.12, aOR 0.69; 95% CI 0.39-1.21), as well as secondary outcomes such as postpartum endometritis (3.0 vs. 2.5%, crude p = 0.61, aOR 1.12; 95% CI 0.49-2.53), postpartum hemorrhage (16.1 vs. 15.8%, crude p = 0.89, aOR 1.07; 95% CI 0.75-1.54), blood loss (479.5 vs. 500 mL, adjusted p = 0.89), and cesarean delivery (40.6 vs. 43.1%, crude p = 0.45, aOR 0.90; 95% CI 0.68-1.19). CONCLUSION: Amnioinfusion was not associated with increased odds of intraamniotic infection compared with intrauterine pressure catheter placement alone. KEY POINTS: · Amnioinfusion involves instilling fluid into the amniotic cavity to relieve variable decelerations.. · Amnioinfusion is not associated with increased odds of chorioamnionitis compared to IUPC alone.. · Amnioinfusion is not associated with increased odds of PPH compared to IUPC placement alone..
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Líquido Amniótico , Catéteres , Corioamnionitis/terapia , Adulto , Cuello del Útero , Cesárea/estadística & datos numéricos , Endometritis/epidemiología , Femenino , Edad Gestacional , Humanos , Infecciones/epidemiología , Modelos Logísticos , Análisis Multivariante , Hemorragia Posparto/epidemiología , Embarazo , Estudios Retrospectivos , Centros de Atención Terciaria , Adulto JovenRESUMEN
OBJECTIVE: The study aimed to examine the incidence of hypertensive disorders of pregnancy in women diagnosed with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2, also known as COVID-19). STUDY DESIGN: This was a retrospective cohort study of all women who delivered at MedStar Washington Hospital Center in Washington, DC from April 8, 2020 to July 31, 2020. Starting April 8, 2020, universal testing for COVID-19 infection was initiated for all women admitted to labor and delivery. Women who declined universal testing were excluded. Hypertensive disorders of pregnancy were diagnosed based on American College of Obstetricians and Gynecologists Task Force definitions.1 Maternal demographics, clinical characteristics, and labor and delivery outcomes were examined. Neonatal outcomes were also collected. Laboratory values from admission were evaluated. Our primary outcome was the incidence of hypertensive disorders of pregnancy among women who tested positive for COVID-19. The incidence of hypertensive disorders of pregnancy was compared between women who tested positive for COVID-19 and women who tested negative. RESULTS: Of the 1,008 women included in the analysis, 73 (7.2%) women tested positive for COVID-19, of which 12 (16.4%) were symptomatic at the time of admission. The incidence of hypertensive disorders of pregnancy was 34.2% among women who tested positive for COVID-19 and 22.9% women who tested negative for COVID-19 (p = 0.03). After adjusting for race, antenatal aspirin use, chronic hypertension, and body mass index >30, the risk of developing any hypertensive disorder of pregnancy was not statistically significant (odds ratio: 1.58 [0.91-2.76]). CONCLUSION: After adjusting for potential confounders, the risk of developing a hypertensive disorder of pregnancy in women who tested positive for COVID-19 compared with women who tested negative for COVID-19 was not significantly different. KEY POINTS: · There is an increased incidence of hypertensive disorders in women who test positive for COVID-19.. · Characteristics of pregnant women with COVID-19 are similar to those with hypertensive disorders.. · Liver function tests were similar between pregnant women with COVID-19 and women without COVID-19..
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COVID-19/epidemiología , Hipertensión Inducida en el Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , District of Columbia/epidemiología , Femenino , Humanos , Incidencia , Embarazo , Estudios Retrospectivos , SARS-CoV-2 , Adulto JovenRESUMEN
PURPOSE: Persistent STAT3 signaling is frequently detected in many cancer types including triple-negative breast cancer, and thus could potentially serve as a viable therapeutic target. We have designed a novel non-peptide compound LLY17 targeting STAT3 using Advanced Multiple Ligand Simultaneous Docking (AMLSD) methods. However, the efficacy of LLY17 has not been evaluated extensively in human and murine triple-negative breast cancer cells. In this study, we tested LLY17 in multiple human and murine triple-negative breast cancer cell lines. METHODS: Human triple-negative breast cancer MDA-MB-468, MDA-MB-231, SUM159, and BT-549 cells, and murine triple-negative breast cancer 4T1 cells were used to study the inhibition effects of LLY17. The inhibition of STAT3 activation of LLY17 was investigated using western blot analysis. Cell viability, apoptosis and migration assays were carried out by MTT assay, Caspase-3/7 assay and wound healing assay, respectively. A mammary fat pad syngeneic mouse model was used to evaluate the antitumor effect of LLY17 in vivo. RESULTS: LLY17 inhibited IL-6-mediated induction of STAT3 phosphorylation but had no effect on IFN-γ-induced STAT1 phosphorylation or EGF-induced ERK phosphorylation. LLY17 inhibited STAT3 phosphorylation and induced apoptosis in human and murine triple-negative breast cancer cells but exhibited minimal toxicity toward Luminal A subtype breast cancer MCF-7 cells. RNAi attenuation experiments supported the requirement of STAT3 for LLY17-mediated inhibition of cell viability in triple-negative breast cancer cells. In addition, LLY17 inhibited cell migration of human and murine triple-negative breast cancer cells. Furthermore, LLY17 suppressed tumor growth and STAT3 phosphorylation of triple-negative breast cancer cells in a mammary fat pad syngeneic mouse model in vivo. CONCLUSIONS: Together, our findings suggest that targeting persistent STAT3 signaling by novel small molecule LLY17 may be a potential approach for the therapy of triple-negative breast cancer.
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Antineoplásicos/farmacología , Factor de Transcripción STAT3/antagonistas & inhibidores , Bibliotecas de Moléculas Pequeñas/farmacología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Interleucina-6/antagonistas & inhibidores , Interleucina-6/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Simulación del Acoplamiento Molecular , Fosforilación/efectos de los fármacos , Factor de Transcripción STAT3/química , Factor de Transcripción STAT3/metabolismo , Bibliotecas de Moléculas Pequeñas/química , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Intraoperative pulmonary artery (PA) hemorrhage is one of the leading reasons for conversion from uniportal VATS to open thoracotomy, especially for the small incision (≤3 cm) uniportal VATS performed by our department. So, We designed a technology called pretreatment clamping of the pulmonary artery, which may be helpful to solve the problem. METHODS: A retrospective analysis of 19 patients who had pulmonary artery bleeding during uniportal thoracoscopic lobectomy in which one group had undergone preventive pulmonary artery clamping, the clamping group (n = 11), and one group which did not receive preventive clamping, the non-clamping group (n = 8). We compared the rates of conversion from the uniportal VATS approach to open thoracotomy or multi-incision operation, duration of pulmonary artery repair, blood loss, length of postoperative hospital stay and postoperative complications of the two groups. RESULTS: Compared to the non-clamping group, the clamping group had lower rates of conversion to open thoracotomy (0% vs 62.5%, p < 0.05) and lower rates of conversion to multi-incision operations (18.2% of non-clamping converted to 2-port approach vs 12.5% of clamping converted to 2-port approach and 12.5% converted to 3-port approach, p < 0.05). Duration of pulmonary artery repair was reduced in the clamping group (10.1 ± 3.2 min vs 18.3 ± 5.5 min, p < 0.05). The clamping group also had decreased blood loss (23.6 ± 11.2 ml vs 47.5 ± 14.9 ml, p<0.05). There were no significant differences in postoperative hospital stay and postoperative complications between the two groups. CONCLUSION: Pretreatment clamping of the pulmonary artery in VATS lobectomy can decrease conversion rates, decrease blood loss, shorten repairing time of the pulmonary artery, and feasibly can be applied in uniportal thoracoscopic lobectomy.
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Hemostasis Quirúrgica/métodos , Neoplasias Pulmonares , Neumonectomía/métodos , Arteria Pulmonar , Pérdida de Sangre Quirúrgica/prevención & control , Constricción , Conversión a Cirugía Abierta , Femenino , Técnicas Hemostáticas , Humanos , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Arteria Pulmonar/cirugía , Estudios Retrospectivos , Cirugía Torácica Asistida por VideoRESUMEN
Background: Fecal microbiota transplant (FMT) appears safe and effective for treatment of recurrent Clostridium difficile infection (RCDI). However, durability, long-term clinical outcomes, and patient satisfaction after FMT are not well described. Methods: Eligible patients who received FMT for RCDI at Emory Hospital between 1 July 2012 and 31 December 2016 were contacted via telephone for a follow-up survey. Of 190 eligible patients, 137 (72%) completed the survey. Results: Median time from last FMT to follow-up was 22 months. Overall, 82% (113/137) of patients at follow-up had no recurrence of C. difficile infection (CDI) post-FMT (non-RCDI group) and 18% (24/137) of patients had CDI post-FMT (RCDI group). Antibiotic exposure for non-CDI infections after FMT was more common in the RCDI group compared to the non-RCDI group (75% vs 38%, P = .0009). Overall, 11% of patients reported improvement or resolution of diagnoses not related to CDI post-FMT, and 33% reported development of a new medical condition or symptom post-FMT. Ninety-five percent of patients (122/128) indicated that they would undergo FMT again, and 70% of these 122 reported that they would prefer FMT to antibiotics as initial treatment if they were to have a CDI recurrence. Conclusions: In this follow-up survey of outcomes after FMT at a median of 22 months follow-up, 82% of patients had durable cure of CDI. Patients with recurrence had more post-FMT antibiotic exposure, underscoring the need for thoughtful antibiotic use and a potential role for prophylactic microbiome enrichment to reduce recurrence.
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Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal , Adulto , Anciano , Anciano de 80 o más Años , Heces , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
Fecal microbiota transplantation (FMT) is increasingly being performed for Clostridium difficile infection in solid organ transplant (SOT) patients; however, little is known about the potential pharmacokinetic or pharmacomicrobial effects this may have on tacrolimus levels. We reviewed the medical records of 10 SOT patients from September 2012-December 2016 who were taking tacrolimus at time of FMT for recurrent C. difficile infection. We compared the differences in tacrolimus concentration/dose ratio (C/D ratio) 3 months prior to FMT vs 3 months after FMT. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/kg/d) was -17.65 (95% CI -1.25 to 0.58) (ng/mL)/(mg/kg/d), P-value .43 by Wilcoxon signed-rank test. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/d) was -0.33 (95% CI -1.25 to 0.58) (ng/mL)/(mg/d), P-value .28 by Wilcoxon signed-rank test. Of these patients, 2/10 underwent allograft biopsy for allograft dysfunction in the year after FMT, with no evidence of allograft rejection on pathology. These preliminary data suggest that FMT may not predictably alter tacrolimus levels and support its safety for SOT patients however further study in randomized trials is needed.
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Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal , Inmunosupresores/sangre , Trasplante de Órganos/efectos adversos , Tacrolimus/sangre , Humanos , Inmunosupresores/farmacocinética , Estudios Retrospectivos , Tacrolimus/farmacocinéticaRESUMEN
PURPOSE OF REVIEW: As healthcare-associated influenza is a serious public health concern, this review examines legal and ethical arguments supporting mandatory influenza vaccination policies for healthcare personnel, implementation issues and evidence of effectiveness. RECENT FINDINGS: Spread of influenza from healthcare personnel to patients can result in severe harm or death. Although most healthcare personnel believe that they should be vaccinated against seasonal influenza, the Centers for Disease Control and Prevention (CDC) report that only 79% of personnel were vaccinated during the 2015-2016 season. Vaccination rates were as low as 44.9% in institutions that did not promote or offer the vaccine, compared with rates of more than 90% in institutions with mandatory vaccination policies. Policies that mandate influenza vaccination for healthcare personnel have legal and ethical justifications. Implementing such policies require multipronged approaches that include education efforts, easy access to vaccines, vaccine promotion, leadership support and consistent communication emphasizing patient safety. SUMMARY: Mandatory influenza vaccination for healthcare personnel is a necessary step in protecting patients. Patients who interact with healthcare personnel are often at an elevated risk of complications from influenza. Vaccination is the best available strategy for protecting against influenza and evidence shows that institutional policies and state laws can effectively increase healthcare personnel vaccination rates, decreasing the risk of transmission in healthcare settings. There are legal and ethical precedents for institutional mandatory influenza policies and state laws, although successful implementation requires addressing both administrative and attitudinal barriers.
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Personal de Salud , Programas de Inmunización , Vacunas contra la Influenza , Gripe Humana/prevención & control , Programas Obligatorios , Enfermedades Profesionales/prevención & control , Personal de Salud/ética , Personal de Salud/legislación & jurisprudencia , Política de Salud , Humanos , Programas de Inmunización/ética , Programas de Inmunización/legislación & jurisprudencia , Programas de Inmunización/organización & administración , Gripe Humana/transmisión , Programas Obligatorios/ética , Programas Obligatorios/legislación & jurisprudencia , Programas Obligatorios/organización & administración , Evaluación de Resultado en la Atención de Salud , Estados UnidosRESUMEN
PURPOSE OF REVIEW: Maternal vaccination is a well-tolerated and effective way to protect mothers, their developing fetuses, and their young infants from infectious diseases. Although influenza vaccine and diphtheria, tetanus, and acellular pertussis (Tdap) vaccine are recommended for all pregnant women, uptake rates in the United States remain low. This review will focus on the rationale, scientific evidence, and perceptions of vaccination during pregnancy. RECENT FINDINGS: Recent studies show that administration of influenza and Tdap vaccines during pregnancy is well tolerated and provides protection to the pregnant woman, her fetus, and young infant. Studies have shown that many pregnant women look to their obstetricians to guide their prenatal care. A strong provider recommendation remains the greatest impetus to increase vaccine uptake. Both healthcare providers and expectant mothers should continue to be educated on the importance and safety of the influenza and Tdap vaccines during pregnancy. SUMMARY: Providers play a central role in advising patients and their families about the importance of maternal vaccination. The strong recommendation of providers and the availability of maternal vaccines in OB/GYN offices are keys to improve vaccine uptake. Attention must be paid to further development of intervention techniques that address unique barriers such as vaccine cost, storage concerns, and misinformation about vaccine safety.
Asunto(s)
Atención Prenatal/métodos , Vacunación/métodos , Actitud del Personal de Salud , Competencia Clínica , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Lactante , Recién Nacido , Aceptación de la Atención de Salud , EmbarazoRESUMEN
OBJECTIVE: Twin survivors of twin-twin transfusion syndrome (TTTS) may be at risk for early onset of cardiovascular disease. The aim of this study was to determine prevalence and risk factors for elevated blood pressure (BP) among children treated with selective laser photocoagulation of communicating vessels. STUDY DESIGN: Data were prospectively collected from surviving children treated for TTTS with laser surgery from 2008 through 2010. Systolic BP (SBP) and diastolic BP (DBP) were obtained from 91 child survivors at age 24 months (±6 weeks) and evaluated based on age, sex, and height percentile. BP percentiles were calculated for each patient and categorized as normal (<95%) or abnormal (>95%). Clinical variables were evaluated using multilevel regression models to evaluate risk factors for elevated BP. RESULTS: BP was categorized as normal in 38% and abnormal in 62% of twin survivors based on percentile for sex, age, and height; a comparable distribution was found for DBP elevation. There were no differences between donor and recipient twins for absolute SBP and DBP or BP classification. In a multivariate analysis, significant risk factors for higher SBP included prematurity (ß -0.54; 95% confidence interval [CI], -0.99 to -0.09; P = .02), higher weight percentile (ß 0.24; 95% CI, 0.05-0.42; P = .01), and presence of cardiac disease (ß 0.50; 95% CI, 0.10-0.89; P = .01). Prematurity was also a significant risk for abnormal DBP (odds ratio, 0.89; 95% CI, 0.80-1.00; P = .05). CONCLUSION: Child survivors of TTTS had elevated SBP and DBP measurements at 2 years of age, with no differences seen between former donor and recipient twins. Prematurity may be a risk factor for elevated BP measurements in this population. Future studies are warranted to ascertain whether these cardiovascular findings persist over time.