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The LIGO-Virgo analyses of signals from compact binary mergers observed so far have assumed isolated binary systems in a vacuum, neglecting the potential presence of astrophysical environments. We present here the first investigation of environmental effects on each of the events of GWTC-1 and two low-mass events from GWTC-2. We find no evidence for the presence of environmental effects. Most of the events decisively exclude the scenario of dynamical fragmentation of massive stars as their formation channel. GW170817 results in the most stringent upper bound on the medium density (â²21 g/cm^{3}). We find that environmental effects can substantially bias the recovered parameters in the vacuum model, even when these effects are not detectable. We forecast that the Einstein Telescope and B-DECIGO will be able to probe the environmental effects of accretion disks and superradiant boson clouds on compact binaries.
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Bacteria and their phage adversaries are engaged in an ongoing arms race, resulting in the development of a broad antiphage arsenal and corresponding viral countermeasures. In recent years, the identification and utilization of CRISPR-Cas systems have driven a renewed interest in discovering and characterizing antiphage mechanisms, revealing a richer diversity than initially anticipated. Currently, these defense systems can be categorized based on the bacteria's strategy associated with the infection cycle stage. Thus, bacterial defense systems can degrade the invading genetic material, trigger an abortive infection, or inhibit genome replication. Understanding the molecular mechanisms of processes related to bacterial immunity has significant implications for phage-based therapies and the development of new biotechnological tools. This review aims to comprehensively cover these processes, with a focus on the most recent discoveries.
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Bacterias , Bacteriófagos , Sistemas CRISPR-Cas , Bacterias/genética , Bacteriófagos/fisiología , Bacteriófagos/genética , Farmacorresistencia Bacteriana/genética , Humanos , Infecciones Bacterianas/inmunología , Infecciones Bacterianas/microbiologíaRESUMEN
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Current chemotherapy treatment regimens have improved survival rates to approximately 80%; however, resistance development remains the primary cause of treatment failure, affecting around 20% of cases. Some studies indicate that loss of the phosphatase and tensin homolog (PTEN) leads to deregulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, increasing the expression of proteins involved in chemoresistance. PTEN loss results in deregulation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and induces hypoxia-inducible factor 1-alpha (HIF-1α) expression in various cancers. Additionally, it triggers upregulation of the Yin Yang 1 (YY1) transcription factor, leading to chemoresistance mediated by glycoprotein p-170 (Gp-170). The aim of this study was to investigate the role of the PTEN/NF-κB axis in YY1 regulation via HIF-1α and its involvement in ALL. A PTEN inhibitor was administered in RS4;11 cells, followed by the evaluation of PTEN, NF-κB, HIF-1α, YY1, and Gp-170 expression, along with chemoresistance assessment. PTEN, HIF-1α, and YY1 expression levels were assessed in the peripheral blood mononuclear cells (PBMC) from pediatric ALL patients. The results reveal that the inhibition of PTEN activity significantly increases the expression of pAkt and NF-κB, which is consistent with the increase in the expression of HIF-1α and YY1 in RS4;11 cells. In turn, this inhibition increases the expression of the glycoprotein Gp-170, affecting doxorubicin accumulation in the cells treated with the inhibitor. Samples from pediatric ALL patients exhibit PTEN expression and higher HIF-1α and YY1 expression compared to controls. PTEN/Akt/NF-κB axis plays a critical role in the regulation of YY1 through HIF-1α, and this mechanism contributes to Gp-170-mediated chemoresistance in pediatric ALL.
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Resistencia a Antineoplásicos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Fosfohidrolasa PTEN , Leucemia-Linfoma Linfoblástico de Células Precursoras , Factor de Transcripción YY1 , Humanos , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Factor de Transcripción YY1/metabolismo , Factor de Transcripción YY1/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Resistencia a Antineoplásicos/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Niño , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , FN-kappa B/metabolismo , Masculino , FemeninoRESUMEN
Breast cancer (BC) is the most common cancer in women, with incidence rates increasing globally in recent years. Therefore, it is important to find new molecules with prognostic and therapeutic value to improve therapeutic response and quality of life. The polyunsaturated fatty acids (PUFAs) metabolic pathway participates in various physiological processes, as well as in the development of malignancies. Although aberrancies in the PUFAs metabolic pathway have been implicated in carcinogenesis, the functional and clinical relevance of this pathway has not been well explored in BC. To evaluate the clinical significance of soluble epoxide hydrolase (EPHX2) expression in Mexican patients with BC using tissue microarrays (TMAs) and digital pathology (DP). Immunohistochemical analyses were performed on 11 TMAs with 267 BC samples to quantify this enzyme. Using DP, EPHX2 protein expression was evaluated solely in tumor areas. The association of EPHX2 with overall survival (OS) was detected through bioinformatic analysis in public databases and confirmed in our cohort via Cox regression analysis. Clear nuclear expression of EPHX2 was identified. Receiver operating characteristics (ROC) curves revealed the optimal cutoff point at 2.847062 × 10-3 pixels, with sensitivity of 69.2% and specificity of 67%. Stratification based on this cutoff value showed elevated EPHX2 expression in multiple clinicopathological features, including older age and nuclear grade, human epidermal growth factor receptor 2 (HER2) and triple negative breast cancer (TNBC) subtypes, and recurrence. Kaplan-Meier curves demonstrated how higher nuclear expression of EPHX2 predicts shorter OS. Consistently, multivariate analysis confirmed EPHX2 as an independent predictor of OS, with a hazard ratio (HR) of 3.483 and a 95% confidence interval of 1.804-6.724 (p < 0.001). Our study demonstrates for the first time that nuclear overexpression of EPHX2 is a predictor of poor prognosis in BC patients. The DP approach was instrumental in identifying this significant association. Our study provides valuable insights into the potential clinical utility of EPHX2 as a prognostic biomarker and therapeutic target in BC.
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Biomarcadores de Tumor , Neoplasias de la Mama , Epóxido Hidrolasas , Humanos , Epóxido Hidrolasas/metabolismo , Epóxido Hidrolasas/genética , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/genética , Persona de Mediana Edad , Pronóstico , Biomarcadores de Tumor/metabolismo , Anciano , Adulto , Núcleo Celular/metabolismo , Regulación hacia Arriba , Regulación Neoplásica de la Expresión Génica , Curva ROC , Anciano de 80 o más Años , Estimación de Kaplan-MeierRESUMEN
The genus, Ochrosia, is widely distributed from the West Indian Ocean throughout tropical Asia to the Middle Southern Pacific region. Ochrosia comprises many island-endemic species, suggesting that long-distance dispersal and isolation after migration are key factors for clarifying the diversification process. However, the phylogeny and biogeography of endemic Ochrosia species have not been evaluated well due to the difficulty of adequate sampling from the entire distribution range of the genus. In this study, we focused on two Ochrosia species endemic to the Bonin (Ogasawara) Islands in the northwest Pacific. The Bonin Islands are of volcanic origins and consist of two islands groups, the Ogasawara and Volcano Islands groups, approximately 300 km apart. Ochrosia nakaiana is endemic to the Ogasawara Islands group, whereas O. hexandra is endemic to the Volcano Islands group. To elucidate the phylogenetic positions of these two endemic Ochrosia species, we conducted molecular phylogenetic studies with dating and biogeographic analyses including other Ochrosia species. The phylogenetic trees showed that the two endemic species had distinct origins; O. nakaiana was closely related to O. oppositifolia and O. iwasakiana, whereas O. hexandra was related to O. mariannensis. Based on the chloroplast DNA phylogeny, the genus, Ochrosia, divided into two major lineages 36.6 million years ago. Further, the two endemic species of the Bonin Islands were independently derived approximately 1-2 million years ago. Ochrosia nakaiana originated from the Southeast Asia, New Caledonia, or other Pacific Islands, while O. hexandra derived from O. mariannensis in Micronesia. We demonstrated different origins of the two endemic Ochrosia species on the Bonin Islands. This study provided an excellent example of the complex origins and speciation of flora in the oceanic islands.
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Apocynaceae , Ochrosia , Apocynaceae/genética , ADN de Cloroplastos/genética , Islas , FilogeniaRESUMEN
The formation of primordial black holes from inflationary fluctuations is accompanied by a scalar induced gravitational wave background. We perform a Bayesian search of such background in the data from Advanced LIGO and Virgo's first, second, and third observing runs, parametrizing the peak in the curvature power spectrum by a log-normal distribution. The search shows no evidence for such a background. We place 95% confidence level upper limits on the integrated power of the curvature power spectrum peak which, for a narrow width, reaches down to 0.02 at 10^{17} Mpc^{-1}. The resulting constraints are stronger than those arising from big bang nucleosynthesis or cosmic microwave background observations. In addition, we find that the constraints from LIGO and Virgo, at their design sensitivity, and from the Einstein Telescope can compete with those related to the abundance of the formed primordial black holes.
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Background: Axillary surgical management in patients with node-positive breast cancer at the time of diagnosis converted to negative nodes through neoadjuvant chemotherapy (NAC) remains unclear. Removal of more than two sentinel nodes (SLNs) in these patients may decrease the false negative rate (FNR) of sentinel lymph node biopsies (SLNBs). We aim to analyse the detection rate (DR) and the FNR of SLNB assessment according to the number of SLNs removed. Methods: A retrospective study was performed from October 2012 to December 2018. Patients with invasive breast cancer who had a clinically node-positive disease at diagnosis and with a complete axillary response after neoadjuvant chemotherapy were selected. Patients included underwent SLNB and axillary lymph node dissection (ALND) after NAC. The SLN was considered positive if any residual disease was detected. Descriptive statistics were used to describe the clinicopathologic features and the results of SLNB and ALND. The DR of SLNB was defined as the number of patients with successful identification of SLN. Presence of residual disease in ALND and negative SLN was considered false negative. Results: A total of 368 patients with invasive breast cancer who underwent surgery after complete NAC were studied. Of them, 85 patients met the eligibility criteria and were enrolled in the study. The mean age at diagnosis was 50.8 years. Systematic lymphadenectomy was performed in all patients, with an average of 10 lymph nodes removed. The DR of SLNB was 92.9%, and the FNR was 19.1. The median number of SLNs removed was 3, and at least, three SLNs were obtained in 42 patients (53.2%). When at least three sentinel nodes were removed, the FNR decreased to 8.7%. Conclusions: In this cohort, the SLN assessment was associated with an adequate DR and a high FNR. Removing three or more SLNs decreased the FNR from 19.1% to 8.7%. Complementary approaches may be considered for axillary lymph node staging after neoadjuvant chemotherapy. The study was approved by our institution's ethics committee (Instituto de Investigacion Sanitaria Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain) (https://clinicaltrials.gov/ct2/show/NCEI:20/0048).
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Neoplasias de la Mama , Biopsia del Ganglio Linfático Centinela , Axila/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/patología , Terapia Neoadyuvante/métodos , Neoplasia Residual/patología , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela/métodosRESUMEN
miRNAs are non-coding RNA sequences of approximately 22 nucleotides that interact with genes by inhibiting their translation through binding to their 3' or 5' UTR regions. Following their discovery, the role they play in the development of various pathologies, particularly cancer, has been studied. In this context, miR-7 is described as an important factor in the development of cancer because of its role as a tumor suppressor, regulating a large number of genes involved in the development and progression of cancer. Recent data support the function of miR-7 as a prognostic biomarker in cancer, and miR-7 has been proposed as a strategy in cancer therapy. In this work, the role of miR-7 in various types of cancer is reviewed, illustrating its regulation, direct targets, and effects, as well as its possible relationship to the clinical outcome of cancer patients.
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MicroARNs , Neoplasias , Regiones no Traducidas 5' , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias/genéticaRESUMEN
Members of the Bcl-2 family are proteins that play an essential role in the regulation of apoptosis, a crucial process in development and normal physiology in multicellular organisms. The essential mechanism of this family of proteins is given by the role of pro-survival proteins, which inhibit apoptosis by their direct binding with their counterpart, the effector proteins of apoptosis. This family of proteins was named after the typical member Bcl-2, which was named for its discovery and abnormal expression in B-cell lymphomas. Subsequently, the structure of one of its members BCL-xL was described, which allowed one to understand much of the molecular mechanism of this family. Due to its role of BCL-xL in the regulation of cell survival and proliferation, it has been of great interest in its study. Due to this, it is important to research its role regarding the development and progression of human malignancies, especially in hematologic malignancies. Due to its variation in expression in cancer, it has been suggested that BCL-xL can or cannot play a role in cancer depending on the cellular or tissue context. This review discusses recent advances in its transcriptional regulation of BCL-xL, as well as the advances regarding the activities of BCL-xL in hematological malignancies, its possible role as a biomarker, and its possible clinical relevance in these malignancies.
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Neoplasias Hematológicas , Proteína bcl-X , Apoptosis/genética , Supervivencia Celular , Neoplasias Hematológicas/genética , Humanos , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteína bcl-X/genética , Proteína bcl-X/metabolismoRESUMEN
Lung cancer is currently the leading cause of cancer death worldwide; it is often diagnosed at an advanced stage and bears poor prognosis. It has been shown that diet is an important environmental factor that contributes to the risk and mortality of several types of cancers. Intake of ω-3 and ω-6 PUFAs plays an important role in cancer risk and progression. Current Western populations have high consumption of ω-6 PUFAs with a ratio of ω-6/ω-3 PUFAs at 15:1 to 16.7:1 This high consumption of ω-6 PUFAs is related to increased cancer risk and progression. However, whether a diet rich in ω-6 PUFAs can contribute to tumor aggressiveness has not been well investigated. We used a murine model of pulmonary squamous cell carcinoma to study the aggressiveness of tumors in mice fed with a diet rich in ω-6 PUFAs and its relationship with oxylipins. Our results shown that the mice fed a diet rich in ω-6 showed a marked increase in proliferation, angiogenesis and pro-inflammatory markers and decreased expression of pro-apoptotic proteins in their tumors. Oxylipin profiling revealed an upregulation of various pro-tumoral oxylipins including PGs, HETEs, DiHETrEs and HODEs. These results demonstrate for the first time that high intake of ω-6 PUFAs in the diet enhances the malignancy of tumor cells by histological changes on tumor dedifferentiation and increases cell proliferation, angiogenesis, pro-inflammatory oxylipins and molecular aggressiveness targets such as NF-κB p65, YY1, COX-2 and TGF-ß.
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Ácidos Grasos Omega-3 , Neoplasias Pulmonares , Animales , Dieta , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6/metabolismo , Ácidos Grasos Omega-6/farmacología , Ratones , Oxilipinas/metabolismoRESUMEN
Yin-Yang transcription factor 1 (YY1) is involved in tumor progression, metastasis and has been shown to be elevated in different cancers, including leukemia. The regulatory mechanism underlying YY1 expression in leukemia is still not understood. Bioinformatics analysis reveal three Hypoxia-inducible factor 1-alpha (HIF-1α) putative binding sites in the YY1 promoter region. The regulation of YY1 by HIF-1α in leukemia was analyzed. Mutation of the putative YY1 binding sites in a reporter system containing the HIF-1α promoter region and CHIP analysis confirmed that these sites are important for YY1 regulation. Leukemia cell lines showed that both proteins HIF-1α and YY1 are co-expressed under hypoxia. In addition, the expression of mRNA of YY1 was increased after 3 h of hypoxia conditions and affect several target genes expression. In contrast, chemical inhibition of HIF-1α induces downregulation of YY1 and sensitizes cells to chemotherapeutic drugs. The clinical implications of HIF-1α in the regulation of YY1 were investigated by evaluation of expression of HIF-1α and YY1 in 108 peripheral blood samples and by RT-PCR in 46 bone marrow samples of patients with pediatric acute lymphoblastic leukemia (ALL). We found that the expression of HIF-1α positively correlates with YY1 expression in those patients. This is consistent with bioinformatic analyses of several databases. Our findings demonstrate for the first time that YY1 can be transcriptionally regulated by HIF-1α, and a correlation between HIF-1α expression and YY1 was found in ALL clinical samples. Hence, HIF-1α and YY1 may be possible therapeutic target and/or biomarkers of ALL.
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Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Factor de Transcripción YY1/metabolismo , Adolescente , Línea Celular Tumoral , Niño , Preescolar , Regulación Neoplásica de la Expresión Génica , Humanos , Lactante , Recién NacidoRESUMEN
We place constraints on the normalized energy density in gravitational waves from first-order strong phase transitions using data from Advanced LIGO and Virgo's first, second, and third observing runs. First, adopting a broken power law model, we place 95% confidence level upper limits simultaneously on the gravitational-wave energy density at 25 Hz from unresolved compact binary mergers, Ω_{CBC}<6.1×10^{-9}, and strong first-order phase transitions, Ω_{BPL}<4.4×10^{-9}. The inclusion of the former is necessary since we expect this astrophysical signal to be the foreground of any detected spectrum. We then consider two more complex phenomenological models, limiting at 25 Hz the gravitational-wave background due to bubble collisions to Ω_{pt}<5.0×10^{-9} and the background due to sound waves to Ω_{pt}<5.8×10^{-9} at 95% confidence level for phase transitions occurring at temperatures above 10^{8} GeV.
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Fully automated closed-loop insulin delivery may offer a novel way to manage diabetes in hospital. However, postprandial glycaemic control remains challenging. We aimed to assess the effect of nutritional intake on postprandial glucose control in hospitalized patients with type 2 diabetes receiving fully closed-loop insulin therapy. The effects of different meal types and macronutrient composition on sensor glucose time-in-target (TIT, 3.9-10.0 mmol/L) and mean sensor glucose were assessed with hierarchical linear models using a Bayesian estimation approach. TIT was lower and the mean sensor glucose slightly higher, after breakfast compared with lunch and dinner, whereas the insulin dose was higher. Across meals, when carbohydrates were replaced by fat, or to a lesser extent by protein, postprandial glucose control improved. For breakfast, a 3.9% improvement in TIT was observed when 10% of the energy from carbohydrates was replaced by fat. Improvements were slightly lower during lunch and dinner (3.2% and 3.4%) or when carbohydrates were replaced by protein (2.2 and 2.7%, respectively). We suggest that reducing carbohydrate at the expense of fat or protein, could further improve glucose control during fully closed-loop insulin therapy in hospital.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Teorema de Bayes , Glucemia , Estudios Cruzados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Insulina , Sistemas de Infusión de Insulina , Comidas , Periodo PosprandialRESUMEN
PURPOSE OF REVIEW: To describe and critically discuss the most recent evidence regarding stone management during the coronavirus disease 2019 (COVID-19) and post-COVID-19 era. RECENT FINDINGS: There is a need to plan for resuming the normal elective stone surgery in the post-COVID era, keeping a clear record of all surgeries that are being deferred and identifying subgroups of surgical priorities, for the de-escalation phase. Telehealth is very useful because it contributes to reduce virus dissemination guaranteeing at the same time an adequate response to patients' care needs. Once the pandemic is over, teleurology will continue to be utilized to offer cost-effective care to urological patients and it will be totally integrated in our clinical practice. SUMMARY: This COVID-19 pandemic represents a real challenge for all national health providers: on the one hand, every effort should be made to assist COVID patients, while on the other hand we must remember that all other diseases have not disappeared in the meanwhile and they will urgently need to be treated as soon as the pandemic is more under control. A correct prioritization of cases when surgical activity will progressively return back to normality is of paramount importance.
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COVID-19 , Toma de Decisiones , Telemedicina , Urología/métodos , Urología/tendencias , Humanos , PandemiasRESUMEN
BACKGROUND: Preclinical research suggests that the efficacy of immune checkpoint inhibitors in breast cancer can be enhanced by combining them with antiangiogenics, particularly in a sequential fashion. We sought to explore the efficacy and biomarkers of combining the anti-PD-L1 durvalumab plus the antiangiogenic bevacizumab after bevacizumab monotherapy for advanced HER2-negative breast cancer. METHODS: Patients had advanced HER2-negative disease that progressed while receiving single-agent bevacizumab maintenance as a part of a previous chemotherapy plus bevacizumab regimen. Treatment consisted of bi-weekly durvalumab plus bevacizumab (10 mg/kg each i.v.). Peripheral-blood mononuclear cells (PBMCs) were obtained before the first durvalumab dose and every 4 weeks and immunophenotyped by flow-cytometry. A fresh pre-durvalumab tumor biopsy was obtained; gene-expression studies and immunohistochemical staining to assess vascular normalization and characterize the immune infiltrate were conducted. Patients were classified as "non-progressors" if they had clinical benefit (SD/PR/CR) at 4 months. The co-primary endpoints were the changes in the percentage T cell subpopulations in PBMCs in progressors versus non-progressors, and PFS/OS time. RESULTS: Twenty-six patients were accrued. Median PFS and OS were 3.5 and 11 months; a trend for a longer OS was detected for the hormone-positive subset (19.8 versus 7.4 months in triple-negatives; P = 0.11). Clinical benefit rate at 2 and 4 months was 60% and 44%, respectively, without significant differences between hormone-positive and triple-negative (P = 0.73). Non-progressors' tumors displayed vascular normalization features as a result of previous bevacizumab, compared with generally abnormal patterns observed in progressors. Non-progressors also showed increased T-effector and T-memory signatures and decreased TREG signatures in gene expression studies in baseline-post-bevacizumab-tumors compared with progressors. Notably, analysis of PBMC populations before durvalumab treatment was concordant with the findings in tumor samples and showed a decreased percentage of circulating TREGs in non-progressors. CONCLUSIONS: This study reporting on sequential bevacizumab+durvalumab in breast cancer showed encouraging activity in a heavily pre-treated cohort. The correlative studies agree with the preclinical rationale supporting an immunopriming effect exerted by antiangiogenic treatment, probably by reducing TREGs cells both systemically and in tumor tissue. The magnitude of this benefit should be addressed in a randomized setting. TRIAL REGISTRATION: (www.clinicaltrials.gov): NCT02802098 . Registered on June 16, 2020.
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Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Antígeno B7-H1/metabolismo , Bevacizumab/efectos adversos , Mama/patología , Neoplasias de la Mama/sangre , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Femenino , Humanos , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/inmunología , Persona de Mediana Edad , Proyectos Piloto , Supervivencia sin Progresión , Prueba de Estudio Conceptual , Receptor ErbB-2/análisis , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunologíaRESUMEN
Series of novel amides of isoferulic acid, where the phenolic hydroxyl was replaced by a difluoromethyl group, were synthesized and their in vitro antibacterial activities assayed against fourteen bacterial strains (six Gram-positive and eight Gram-negative). A one-pot methodology was developed to obtain the 3'-(difluoromethyl)-4'-methoxycinnamoyl amides using Deoxofluor® as a fluorinating agent. The N-isopropyl, N-isopentyl, and N-(2-phenylethyl) amides 11b, 11d and 11g were the most active and selective against Mycobacterium smegmatis (MIC = 8 µg/mL) with 11b and 11g displaying negligible or no cytotoxicity against HepG2 and A549 cells. Thirteen analogs of N-isopropylamide 11b were also synthesized and their antibacterial activity assayed. Results show that the difluoromethyl moiety enhanced antibacterial activity and selectivity towards M. smegmatis, changing the microorganism inhibition profile of the parent compound. The selectivity exhibited by some of the compounds towards M. smegmatis makes them potential leads in the search for new narrow spectrum antibiotics against M. tuberculosis.
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Amidas/farmacología , Antibacterianos/farmacología , Mycobacterium smegmatis/efectos de los fármacos , Amidas/síntesis química , Amidas/química , Antibacterianos/síntesis química , Antibacterianos/química , Antineoplásicos/química , Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Células Hep G2 , Humanos , Pruebas de Sensibilidad Microbiana , Mycobacterium smegmatis/patogenicidad , Relación Estructura-ActividadRESUMEN
PURPOSE OF REVIEW: The most relevant recent findings on the use of extracorporeal shock wave lithotripsy (ESWL) in adult population to provide an insight of its role in the current and future of stone treatment. Comparing ESWL with other modalities is not in the scope of this review. RECENT FINDINGS: We conducted a PubMed/Embase search and reviewed recent publications that include relevant information on the development of ESWL. Low-rate shock waves improve stone breakage, ramping energy modalities improve stone fragmentation and have lower incidence of hematoma and kidney injury. Transgluteal approach is suggested to improve stone-free rates for distal ureteral stones in a single session. Proper coupling is the most important technical aspect of the treatment and coupling improvement can be achieved by optical monitorization. Triple D score is a promising tool in proper patient selection, but external validation is needed. Predictive information arising from computed tomography scans has been refined by the variant coefficient of stone density and 3D texture analysis that might improve outcomes in the future. SUMMARY: Recent evidence suggests that modifying techniques and protocols, and better patient selection are the current trends for improving ESWL outcomes. EWSL will keep its role as the single noninvasive treatment in stone management with room for outcome improvement in the future.
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Litotricia , Cálculos Ureterales , Adulto , Humanos , Riñón , Selección de Paciente , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Cálculos Ureterales/terapiaRESUMEN
In this work, we have characterized the calcium carbonate (CaCO3) precipitates over time caused by reaction-driven precipitation and dissolution in a micromodel. Reactive solutions were continuously injected through two separate inlets, resulting in transverse-mixing induced precipitation during the precipitation phase. Subsequently, a dissolution phase was conducted by injecting clean water (pH = 4). The evolution of precipitates was imaged in two and three dimensions (2-, 3-D) at selected times using optical and confocal microscopy. With estimated reactive surface area, effective precipitation and dissolution rates can be quantitatively compared to results in the previous works. Our comparison indicates that we can evaluate the spatial and temporal variations of effective reactive areas more mechanistically in the microfluidic system only with the knowledge of local hydrodynamics, polymorphs, and comprehensive image analysis. Our analysis clearly highlights the feedback mechanisms between reactions and hydrodynamics. Pore-scale modeling results during the dissolution phase were used to account for experimental observations of dissolved CaCO3 plumes with dissolution of the unstable phase of CaCO3. Mineral precipitation and dissolution induce complex dynamic pore structures, thereby impacting pore-scale fluid dynamics. Pore-scale analysis of the evolution of precipitates can reveal the significance of chemical and pore structural controls on reaction and fluid migration.
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Carbonato de Calcio , Dispositivos Laboratorio en un Chip , Precipitación Química , Cinética , Minerales , SolubilidadRESUMEN
Several studies suggest that reproductive performance in small-scale dairy farms is low reducing the farms' profitability. Therefore, identifying risk factors associated with low reproductive performance is a key step to implement an improved reproductive management program. Accordingly, the aim of the present study was to identify the main risk factors affecting the reproductive performance of cows in small-scale dairy farms. Ninety-six dairy farms were incorporated into this study, and data from 1263 lactations were collected with different events as potential risk factors. Logistic regression models were used to assess the association (odds ratio, OR) and impact (population attributable fraction, PAF) between the potential risk factors and the reproductive variables. The main risk factors associated with assisted calving were male calf and primiparous cows (OR = 1.7, PAF = 0.315 and OR = 1.5, PAF = 0.131, respectively), while for retained fetal membranes (RFM) were assisted calving and abortion (OR = 4.5, PAF = 0.440 and OR = 8.1, PAF = 0.239, respectively). The main risk factors for days to first service over 70 days in milk were low body condition score at calving (BCS ≤ 2.5) and primiparous cows (OR = 2.2, PAF = 0.285 and OR = 1.4; PAF = 0.096, respectively), while for days open over 110 days in milk were low BCS at calving (BCS ≤ 2.5) and primiparous cows (OR = 1.7, PAF = 0.213 and OR = 1.4; PAF = 0.096, respectively) The main risk factor for non-pregnant cows at first service was RFM (OR = 1.7; PAF = 0.059). In conclusion, assisted calving, male calf, BCS ≤ 2.5 and RFM were the main risk factors associated with reduced reproductive performance in small-scale dairy farms in tropical and subtropical regions of Mexico.
Asunto(s)
Bovinos/fisiología , Industria Lechera/métodos , Reproducción , Animales , Femenino , México , Factores de RiesgoRESUMEN
OBJECTIVES: A Neisseria gonorrhoeae antimicrobial susceptibility quality control comparison programme was re-established in Latin America and the Caribbean to ensure antimicrobial susceptibility data produced from the region are comparable nationally and internationally. METHODS: Three panels, consisting of N. gonorrhoeae isolates comprising reference strains and other characterised isolates were sent to 11 participating laboratories between 2013 and 2015. Antimicrobial susceptibilities for these isolates were determined using agar dilution, Etest or disc diffusion methods. Modal minimum inhibitory concentrations (MICs) for each panel isolate/antibiotic combination were calculated. The guidelines of the Clinical and Laboratory Standards Institute were used for interpretations of antimicrobial susceptibility. The agreement of MICs with the modal MICs was determined for each of the participating laboratories as well as for each of the antibiotics tested. RESULTS: Five of 11 laboratories that participated in at least one panel had an overall average agreement between participants' MIC results and modal MICs of >90%. For other laboratories, agreements ranged from 60.0% to 82.4%. The proportion of agreement between interpretations for all the antibiotics, except penicillin and tetracycline, was >90%. The percentages of agreement between MIC results and their modes for erythromycin, spectinomycin, cefixime and azithromycin were >90%. Tetracycline, ceftriaxone and ciprofloxacin agreement ranged from 84.5% to 89.1%, while penicillin had 78.8% agreement between MICs and modal MICs. CONCLUSIONS: The participating laboratories had acceptable results, similar to other international quality assurance programmes. It is important to ensure continuation of the International Gonococcal Antimicrobial Susceptibility Quality Control Comparison Programme to ensure that participants can identify and correct any problems in antimicrobial susceptibility testing for N. gonorrhoeae as they arise and continue to generate reproducible and reliable data.