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Ischemic acute kidney injury is common, deadly, and accelerates the progression of chronic kidney disease, yet has no specific therapy. After ischemia, reperfusion is patchy with early and persistent impairment in regional renal blood flow and cellular injury. We tested the hypothesis that intrarenal coagulation results in sustained renal ischemia following reperfusion, using a well-characterized model. Markedly decreased, but heterogeneous, microvascular plasma flow with microthrombi was found postischemia by intravital microscopy. Widespread tissue factor expression and fibrin deposition were also apparent. Clotting was accompanied by complement activation and inflammation. Treatment with exosomes derived from renal tubular cells or with the fibrinolytic urokinase, given 24 h postischemia when renal failure was established, significantly improved microvascular flow, coagulation, serum creatinine, and histological evidence of injury. These data support the hypothesis that intrarenal clotting occurs early and the resultant sustained ischemia is a critical determinant of renal failure following ischemia; they demonstrate that the coagulation abnormalities are amenable to therapy and that therapy results in improvement in both function and postischemic inflammation.

Rethink family mathematics nights by drawing on an asset-based perspective in a virtual environment, centering multilingualism and community mathematics knowledge.

Supplementary Table from Epigenetic Activation of Plasmacytoid DCs Drives IFNAR-Dependent Therapeutic Differentiation of AML

Supplementary Figure from Epigenetic Activation of Plasmacytoid DCs Drives IFNAR-Dependent Therapeutic Differentiation of AML

Supplementary Table S1

Supplementary Figure S5 PDF file - 32K, PLX4032 decreases occupancy of the HER3 gene promoter in SW1736 thyroid cancer cells. A, CtBP1 or CtBP2 chromatin immunoprecipitation assays were performed in SW1736 cells treated with or without 2 ��M PLX4032 for 24 or 48 h as described in Figure 5F. Graph shows normalized Q-RT-PCR HER3 data of the immunoprecipitated complexes compared to input lysate. Data represent mean +/- SD of two independent biological replicates performed in quintuplicate. ***p

Supplementary Methods and References PDF File - 39K, Supplementary Methods and References

Supplementary Figures 1-12

Supplementary Figure 3. Pano induced pancreatic tumor cell apoptosis.

Supplementary Figure 2. Pancreatic cells are resistant to VV-gp100 oncolysis but sensitive to CAR T cell-mediated cytotoxicity.

Supplementary Figure 4. Pano did not enhance the cytotoxicity of CARaMEL cells nor oncolysis of VV-gp100.

Supplementary Figure 1. Panc02-Her2, KPC-Her2 and 24JK-Her2 cells express comparable levels of Her2.

Supplementary Figure 5. Pano did not alter Her2 or H2-Db expression on Panc02-Her2 tumor cells in vivo and CARaMEL cells were detectable over 100 days in ACTIV+ Pano treated mice.

Supplementary Figure 8. Proposed mechanisms and clinical application for the ACTIV+Pano treatment.

Supplementary Figure 7. No cytokine storm was observed in WAP- and MMTV-Her2 mice post the ACTIV+Pano treatment.

Resumen Introduccion Los multiples intentos durante la canalizacion periferica pueden producir importantes consecuencias que afectan a pacientes, familiares y profesionales, por ello se planteo la necesidad de conocer la dimension de este problema en una unidad de cuidados intensivos pediatricos (UCIP). Objetivos El objetivo principal fue describir la canalizacion de cateter venoso periferico y cateter central de insercion periferica en ninos de UCIP. Como objetivos secundarios se propuso determinar la proporcion de exito en el primer intento de canalizacion, cuantificar los pacientes que presentan via venosa dificil (VVD), asi como explorar la asociacion entre la aparicion de la VVD y las caracteristicas sociodemograficas, las relativas a la tecnica y a las enfermeras. Metodo Estudio descriptivo transversal. Mediante muestreo consecutivo se reclutaron pacientes entre 0 y 18 anos ingresados en UCIP que precisaron canalizacion de acceso venoso periferico. Para ello se utilizo un cuestionario ad hoc incluyendo la presencia de VVD como variable independiente. Resultados Se recogieron 163 canalizaciones venosas. El 55,8% (91) se realizaron en pacientes menores de 1 ano. El 38,7% (63) acerto en el primer intento y el 36,8% (60) presentaron VVD. Cuando aparecia VVD el 85% (51) de los pacientes tuvieron complicaciones, la mediana de tiempo para la canalizacion mediante cateter venoso periferico corto fue de 30 minutos [15-53] y se precisaron 2 o mas enfermeras en el 80% (48) de las ocasiones. Conclusiones Se encontro un bajo porcentaje de acierto al primer intento y una proporcion elevada de VVD. Aparecia un mayor numero de enfermeras y de tiempo empleado durante la canalizacion y un aumento de las complicaciones si el paciente presentaba VVD. Se encontro asociacion estadisticamente significativa entre VVD y edad, peso, mala perfusion, vena no visible ni palpable, puntuacion en la escala DIVA ≥ 4, historia de VVD, complicaciones, numero de enfermeras y tiempo empleado.

Chlorinated organic compounds (COCs) are among the more toxic organic compounds frequently found in soil and groundwater. Among these, toxic and low-degradable chlorobenzenes are commonly found in the environment. In this work, an innovative process using hydrogen peroxide as the oxidant, ferrioxalate as the catalyst and a visible light-emitting diode lamp (Vis LED) was applied to successfully oxidize 124-trichlorobenzene (124-TCB) in a saturated aqueous solution of 124-TCB (28 mg L−1 ) at a neutral pH. The influence of a hydrogen peroxide (HP) concentration (61.5–612 mg L−1 ), Fe3+ (Fe) dosage (3–10 mg L−1 ), and irradiation level (Rad) (I = 0.12 W cm−2 and I = 0.18 W cm−2 ) on 124-TCB conversion and dechlorination was studied. A D–Optimal experimental design combined with response surface methodology (RSM) was implemented to maximize the quality of the information obtained. The ANOVA test was used to assess the significance of the model and its coefficients. The maximum pollutant conversion at 180 min (98.50%) was obtained with Fe = 7 mg L−1 , HP = 305 mg L−1 , and I = 0.12 W cm−2 . The effect of two inorganic anions usually present in real groundwater (bicarbonate and chloride, 600 mg L−1 each) was investigated under optimized operating conditions. A slight reduction in the 124-TCB conversion after 180 min of reaction was noticed in the presence of bicarbonate (8.31%) and chloride (7.85%). Toxicity was studied with Microtox®(Azur Environmental, Carlsbad, CA, USA) bioassay, and a remarkable toxicity decrease was found in the treated samples, with the inhibition proportional to the remaining 124-TCB concentration. That means that nontoxic byproducts are produced in agreement with the high dechlorination degrees noticed.

There is significant environmental concern about chlorinated organic compounds (COCs) in wastewater, surface water, and groundwater due to their low biodegradability and high persistence. In this work, 1,2,4-trichlorobenzene (124-TCB) was selected as a model compound to study its abatement using wet peroxide oxidation at neutral pH with goethite as a heterogeneous catalyst, which was enhanced with visible monochromatic light-emitting diode (LED) light (470 nm). A systematic study of the main operating variables (oxidant and catalyst concentration and irradiance) was accomplished to investigate their influence in the abatement of 124-TCB in water. The reaction was carried out in a well-mixed reactor of glass irradiated by a visible LED light. The hydrogen peroxide concentration was tested from 0 to 18 mM, the goethite concentration within the range 0.1–1.0 g·L−1 and the irradiance from 0.10 to 0.24 W·cm−2 at neutral pH. It was found that this oxidation method is a very efficient technique to abate 124-TCB, reaching a pollutant conversion of 0.9 when using 0.1 g·L−1 of goethite, 18 mM of H2O2, and 0.24 of W·cm−2 . Moreover, the system performance was evaluated using the photonic efficiency (ratio of the moles of 124-TCB abated and the moles of photons arriving at the reactor window). The maximum photonic efficiencies were obtained using the lowest lamp powers and moderate to high catalyst loads. Fil: Lorenzo, David. Universidad Complutense de Madrid; España Fil: Santos, Aurora. Universidad Complutense de Madrid; España Fil: Sánchez-Yepes, Andrés. Universidad Complutense de Madrid; España Fil: Conte, Leandro Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Domínguez, Carmen María. Universidad Complutense de Madrid; España

Establishment of the hemochorial uterine–placental interface requires exodus of trophoblast cells from the placenta and their transformative actions on the uterus, which represent processes critical for a successful pregnancy, but are poorly understood. We examined the involvement of CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) in rat and human trophoblast cell development. The rat and human exhibit deep hemochorial placentation. CITED2 was distinctively expressed in the junctional zone (JZ) and invasive trophoblast cells of the rat. Homozygous Cited2 gene deletion resulted in placental and fetal growth restriction. Small Cited2 null placentas were characterized by disruptions in the JZ, delays in intrauterine trophoblast cell invasion, and compromised plasticity. In the human placentation site, CITED2 was uniquely expressed in the extravillous trophoblast (EVT) cell column and importantly contributed to the development of the EVT cell lineage. We conclude that CITED2 is a conserved regulator of deep hemochorial placentation.

Probiotic cellulose (PC), a living material (LM) consisting of probiotics integrated into bacterial cellulose, is the first example where life (probiotic proliferation) is the input to tune the viscoelasticity of the biomaterial. The gradual proliferation of probiotics within the matrix acts as a key modulator of the cellulose viscoelasticity, providing from celluloses with lower-than-matrix viscoelasticity to celluloses with viscoelastic moduli closer to those of elastic solids. This concept is a promising approach to producing living bio-ink with tunable viscoelastic response of special interest for specific applications such as 3D printing. In contrast to the most common hydrogels with stimuli-tunable mechanical properties, which require external stimuli such as mechanical stress, UV radiation, or heat, this living bio-ink only requires time to tune from a fluid-like into a solid-like biomaterial.

Histological analysis of bone tissue has been used to explore a variety of questions relating to age-at-death, habitual behaviors, health, and nutritional stress. Identification of intact and fragmentary osteons is of key interest to many researchers in these studies, yet the definitions of these features vary between researchers making cross-study comparisons problematic. Furthermore, histological variable definitions are often ambiguous or require subjective classifications by the observer. As a result, and as indicated by previous studies, observer error and misclassification of certain variables, namely intact and fragmentary osteons, can be significant. This study proposes new definitions for intact and fragmentary osteons that are designed to limit observer subjectivity and also explore efficacy of combining osteon types into one variable. A sample of 30 6th rib cross-sections from a modern forensic population was used to test the validity of the proposed definitions. Observations of intact osteon population density (OPD(I)) and fragmentary osteon population density (OPD(F)) were made by three observers for each cross-section. These observations were used to explore the interobserver error associated with the proposed definitions and determine if combining variables into one variable (OPD) mitigates persisting classification difficulties. Results indicate that the proposed definitions significantly reduce interobserver error and misclassification of intact and fragmentary osteons. However, the interobserver error associated with fragmentary osteons is still high. Evaluation of the variables independently indicates that combining variables has potential to reduce the predictive strength of an age estimation model and the ability to interpret age-related bone remodeling.

OBJECTIVE To explore the hypothesis that using a large, three-dimensional (3D), ultra-high-definition (4K), heads-up display (HUD) system in a real-life setting may be associated with a significant reduction in light intensity (LI) delivered during various types of eye surgery. METHODS Single center, post-learning curve observational study of 142 independent consecutive cases: 73 cataracts and 69 vitrectomies (VR). For each group, the only variable setting was the LI. The LI delivered by each source was calibrated in lumens (lm). RESULTS In the VR group, the delivered LI dramatically decreased from the 80% reference to 27.8%±13.2% (P

Glycosylation of recombinant metalloproteins by means of Escherichia coli has been reported for the first time. This process is switched off by Cd2+ ions and modulated by the proteins’ metal-binding preference towards Zn2+ or Cu+ ions.

Dietary phosphorus restriction and phosphorus binders are commonly prescribed for patients with chronic kidney disease (CKD). However, occurrences of non-adherence to these interventions are common. As low-phosphorus (LP) diets have been consistently experimentally shown in vitro to increase intestinal phosphorus absorption efficiency, a bout of non-adherence to diet or binders may cause an unintended consequence of enhanced intestinal phosphorus absorption. Thus, we aimed to determine the effect of a single bout of high-phosphorus (HP) intake after acclimation to a LP diet. Male Sprague Dawley rats with 5/6 nephrectomy (

This study aimed to describe which infants with a skull fracture (1) receive a child abuse pediatrician (CAP) consultation, (2) receive a skeletal survey, and (3) re-present to medical care before age 3 years with concerns for physical abuse.We conducted a retrospective chart review of infants younger than 12 months who presented to the emergency department between January 1, 2005, and December 30, 2015, with a skull fracture. Medical records were reviewed for the skull fracture presentation and for all future medical evaluations at the same institution with concerns for physical abuse until 3 years of age.Of 366 infants with a skull fracture, a CAP was contacted for 272 (74%) and 76 (20.8%) infants who received a skeletal survey. Factors associated with skeletal survey acquisition included younger age (6 months), no history to explain the skull fracture, other injuries on examination, and social risk factors. Six children (1.6%) re-presented to medical care with concerns of physical abuse before age 3 years. Five of these infants did not have a skeletal survey at the time of their skull fracture, and 1 was likely a case of missed physical abuse at the time of the skull fracture.Most skull fractures in infancy occur accidentally, and a skeletal survey may not be necessary for every infant. Obtaining a thorough history including social risk factors, performing a complete physical examination, and consulting with a CAP is an effective first step in the evaluation of physical abuse in infants with skull fractures.

Developing an efficient transformation system is vital in genetically engineering recalcitrant crops, particularly trees. Here, we outline an Agrobacterium tumefaciens-based stable plant transformation methodology for citrus genetic engineering. The process was optimized to suit the requirements of fourteen citrus varieties by establishing appropriate infection, co-cultivation, selection, and culture media conditions. The procedure includes transforming seedling-derived epicotyl segments with an A. tumefaciens strain, then selecting and regenerating transformed tissues. Transgenic shoots were further identified by a visual reporter (e.g., β-glucuronidase) and confirmed by Northern and Southern blot analysis. Transgene integrations among the transgenic lines ranged between one to four. The methodology can yield transformation efficiencies of up to 11%, and transgenic plants can be recovered as early as six months, depending on the variety. In addition, we show that incorporating A. tumefaciens helper virulence genes (virG and virE), spermidine, and lipoic acid in the resuspension buffer before transformation improved the transformation efficiency of specific recalcitrant cultivars, presumably by enhancing T-DNA integration and alleviating oxidative stress on the explant tissues. In conclusion, the optimized methodology can be utilized to engineer diverse recalcitrant citrus varieties towards trait improvement or functional genetics applications.

Introduction In the first few months after a heart surgery, hospital readmissions and are common. To reduce these events, we developed an early follow-up protocol after discharge based on attention in our cardiological day hospital (CDH), which allows clinical and analytical assessment, monitoring and intravenous treatment if needed, at successive visits. The objective of the study is to assess the protocol impact on the rate of early readmissions, after its implementation in January of 2016. Methods Patients in our area discharged after heart surgery between 2013 and 2019 were included. They were divided into two groups, one with conventional follow-up and one with initial follow-up in CDH. Baseline clinical characteristics, type of surgery and surgical risk were compared. The primary endpoint was the time to the first any-cause readmission. The follow-up time was 200 days from discharge. Quantitative variables were compared using Student's t test and categorical variables using chi-square test. Cox proportional hazards model was used for multivariate analysis. Results 436 patients, 166 with conventional and 270 with CDH follow-up, were included. Baseline characteristics are shown in the table. We found a trend of decreasing readmissions in the CDH group (23,5% in conventional group, 16,3% in CDH group, HR 0,74; CI 95%: 0,48–1,14, p 0,19) although statistical significance was not achieved. In multivariate analysis, the variables independently associated (p1.13, hospital length of stay >14 days and age>73 years. The time to a first cardiological assessment after discharge decreased significantly in the CDH group (64 vs 18 days, p Conclusions In patients followed in CDH after heart surgery, there is a trend towards less readmissions in the first months after discharge. Some baseline characteristics have been shown to be independently associated with the risk of readmission, which will help us to identify the most at-risk patients, on which an intervention could have a greater benefit. Funding Acknowledgement Type of funding sources: None.

Introduction and objectives Readmission rates at 30 days after admission for heart failure (HF) are high. Patients admitted in Cardiology are usually younger and with lower comorbidity than the total population with HF. Our department leads a multidisciplinary program for the management of HF (MHFP), based on early post-discharge follow-up in a day hospital, for clinical-analytical assessment, optimization and titration of pharmacological treatment, structured education, promotion of self-care and intravenous treatment if appropriate. The objective of this study is to assess the impact of the MHFP on all cause 30-day readmission rate in our patients (MHFP group), compared with the rest of the Cardiology units in our region (control group). Methods All discharges with HF main diagnosis in our region were analyzed through anonymized consultation of the Minimum Basic Data Set (a public administrative data base) in the period 2009–2015. The first admission of each patient in the period was identified as index admission, excluding patients who died at that admission and selecting only discharges by Cardiology. Epidemiological characteristics, comorbidities and hospital length of stay were compared in the two groups. The outcome variable was the time to first readmission for any cause in the first 30 days after discharge from index admission. Quantitative variables were compared using Student's t and categorical variables with χ2. For the multivariate analysis, Cox method was used. Results We included 15,440 patients, 474 in the MHFP group and 14,966 in the control group. The epidemiological characteristics and main comorbidities were compared, and the results are shown in the table. Readmission rate was significantly lower in the MHFP group (9.9 vs 14.2%, HR 0.72, 95% CI: 0.54–0.96 in multivariate analysis). The variables independently associated with an increase in 30-day readmissions were the age-adjusted Charlson index and chronic kidney disease. Conclusions Over a period of 6 years, in patients with HF, discharged by Cardiology, a MHFP significantly reduced all cause 30-day readmissions. Funding Acknowledgement Type of funding sources: None.

Introduction and objectives Readmission rates at 30 days after heart failure (HF) hospitalizations are high. Disease management programs have shown to reduce them; however, the results of clinical trials are difficult to extrapolate to the entire population with HF. Our hospital has a multidisciplinary program for HF management (MHFP) led by the Cardiology Department, based on early post-discharge follow-up in a day hospital, for clinical-analytical assessment, optimization and titration of pharmacological treatment, structured education, promotion of self-care and intravenous treatment if appropriate. The objective of this study is to assess the impact of the MHFP on our patients all cause 30-day readmission rate (MHFP group), compared with the rest of our region (control group). Methods All discharges with HF as main diagnosis in our region were analysed through anonymized consultation of the Minimum Basic Data Set (an administrative public data base) in the period 2009–2015. The first admission of each patient in the period was identified as index admission. Patients who died in the index admission were excluded. Epidemiological characteristics, comorbidities and hospital stay were compared in the two groups. The outcome variable was the time to first readmission in the first 30 days after discharge. Quantitative variables were compared using Student's t and categorical variables with χ2. Cox method was used for multivariate analysis. Results We included 62,162 patients, 1,447 in the MHFP group and 60,715 in the control group. Epidemiological characteristics and main comorbidities were compared, and the results are shown in the table. Readmission rate was significantly lower in the MHFP group (13.5 vs 16%, HR 0.85, 95% CI 0.74–0.98 in multivariate analysis). The variables independently associated with an increase in readmissions at 30 days were age adjusted Charlson index, hospital length of stay in index admission and several comorbidities (obstructive pulmonary disease, myocardial infarction, and renal failure) Conclusions Over a period of 6 years, a MHFP significantly reduced 30-day readmissions after admission for HF, in its reference area. The generalization of these programs could have a relevant impact on costs reduction. Funding Acknowledgement Type of funding sources: None.

Nonunion describes bone fractures that fail to heal, resulting in the fracture callus failing to fully ossify or, in atrophic cases, not forming altogether. Fracture healing is regulated, in part, by the balance of proinflammatory and anti-inflammatory processes occurring within the bone marrow and surface cell populations. We sought to further understand the role of osteoimmunology (i.e., study of the close relationship between the immune system and bone) by examining immune cell gene expression via single-cell RNA sequencing of intramedullary canal tissue obtained from human patients with femoral nonunions. Intramedullary canal tissue samples obtained by reaming were collected at the time of surgical repair for femur fracture nonunion (n = 5) or from native bone controls when harvesting autologous bone graft (n = 4). Cells within the samples were isolated and analyzed using the Chromium Single-Cell System (10x Genomics Inc.) and Illumina sequencers. Twenty-three distinct cell clusters were identified, with higher cell proportions in the nonunion samples for monocytes and CD14 + dendritic cells (DCs), and lower proportions of T cells, myelocytes, and promyelocytes in nonunion samples. Gene expression differences were identified in each of the cell clusters from cell types associated with osteoimmunology, including CD14 + DC, monocytes, T cells, promyelocytes, and myelocytes. These results provide human-derived gene profiles that can further our understanding of pathways that may be a cause or a consequence of nonunion, providing the clinical rationale to focus on specific components of osteoimmunology. Clinical significance: The novel single-cell approach may lead to clinically relevant diagnostic biomarkers during earlier stages of nonunion development and/or investigation into therapeutic options.