Race is an important predictor of breastfeeding, with most black women reporting that they "preferred bottle-feeding." Efforts to increase breastfeeding of infants in the black community should help narrow the racial gap in infant mortality.
BACKGROUND Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a significant advancement in the control of noncompressible truncal hemorrhage. However, its ischemic burden and reperfusion injury following balloon deflation limits its utilization. Partial restoration of aortic flow during REBOA has the potential to balance hemorrhage control and ischemia. This study validates the mechanics, physiology, and optimal partial flow rates using a prototype partial REBOA (pREBOA) device. METHODS Twenty-five swine underwent placement of aortic flow probes and zone 1 pREBOA. Experiment 1 (N = 5) animals were not injured and assessed the tested the catheters ability to titrate and control flow. Experiment 2 (N = 10) added 20% hemorrhage and either solid organ, or abdominal vascular injury to compare flow rate and rebleeding from injuries. Experiment 3 (N = 10) swine were similarly prepared, hemorrhaged, and underwent pREBOA at set partial flow rates for 2 hours followed by complete deflation for 30 minutes. RESULTS Balloon volume at minimum flow (mean, 0.09 L/min) was 3.5 mL to 6.0 mL. Half maximal flow was achieved with 56.5% of maximum balloon inflation. Partial REBOA allowed very fine titration of flow rates. Rebleeding occurred at 0.45 L/min to 0.83 L/min. Distal flow of 0.7 L/min had 50% survival, 0.5 had 100% survival, and 0.3 L had 50% survival with mean end lactates of 9.6, 12.6, and 13.3, respectively. There was a trend toward hyperkalemia and hypocalcemia in nonsurvivors. CONCLUSION The pREBOA device demonstrated a high level of titratability for restoration of aortic flow. An optimal partial flow of 0.5 L/min was effective at hemorrhage control while limiting the burden of ischemic injury, and extending the tolerable duration of zone 1 occlusion. Aggressive calcium supplementation prior to and during partial occlusion and reperfusion may be warranted to prevent hyperkalemic arrest.
Retinoic acid receptor-related-orphan-receptor-C (RORγt) is the key transcription factor that is driving the differentiation of IL-17 producing T-helper 17 (Th17) cells that are implicated in the pathology of various autoimmune and inflammatory diseases. Based on the importance of RORγt in promoting Th17-driven pathology, there is considerable interest to develop low-molecular-weight compounds with the aim of inhibiting the transcriptional activity of this nuclear hormone receptor. In this article, we describe the in vitro and in vivo pharmacology of a potent and selective small-molecular-weight RORγt inverse agonist. The compound binds to the ligand binding domain (LBD) of RORγt leading to displacement of a co-activator peptide. We show for the first time that a RORγt inverse agonist down-regulates permissive histone H3 acetylation and methylation at the IL17A and IL23R promoter regions, thereby providing insight into the transcriptional inhibition of RORγt-dependent genes. Consistent with this, the compound effectively reduced IL-17A production by polarized human T-cells and γδT-cells and attenuated transcription of RORγt target genes. The inhibitor showed good in vivo efficacy in an antigen-induced arthritis model in rats and reduced the frequencies of IL-17A producing cells in ex vivo recall assays. In summary, we demonstrate that inhibiting RORγt by a low-molecular-weight inhibitor results in efficient and selective blockade of the pro-inflammatory Th17/IL-17A pathway making it an attractive target for Th17-mediated disorders.
Introduction. An increasing number of studies are utilizing different magnetic resonance (MR) methods to quantify bone marrow fat due to its potential role in osteoporosis. Our aim is to compare the measurements of bone marrow fat among T1-weighted magnetic resonance imaging (MRI), modified Dixon method (also called fat fraction MRI (FFMRI)), and magnetic resonance spectroscopy (MRS). Methods. Contiguous MRI scans were acquired in 27 Caucasian postmenopausal women with a modified Dixon method (i.e., FFMRI). Bone marrow adipose tissue (BMAT) of T1-weighted MRI and bone marrow fat fraction of the L3 vertebra and femoral necks were quantified using SliceOmatic and Matlab. MRS was also acquired at the L3 vertebra. Results. Correlation among the three MR methods measured bone marrow fat fraction and BMAT ranges from 0.78 to 0.88 (P < 0.001) in the L3 vertebra. Correlation between BMAT measured by T1-weighted MRI and bone marrow fat fraction measured by modified FFMRI is 0.86 (P < 0.001) in femoral necks. Conclusion. There are good correlations among T1-weighted MRI, FFMRI, and MRS for bone marrow fat quantification. The inhomogeneous distribution of bone marrow fat, the threshold segmentation of the T1-weighted MRI, and the ambiguity of the FFMRI may partially explain the difference among the three methods.
a b s t r a c tPurpose: The aims of this study are to evaluate the stability of radiomic features from Apparent Diffusion Coefficient (ADC) maps of cervical cancer with respect to: (1) reproducibility in inter-observer delineation, and (2) image pre-processing (normalization/quantization) prior to feature extraction. Materials and methods: Two observers manually delineated the tumor on ADC maps derived from pretreatment diffusion-weighted Magnetic Resonance imaging of 81 patients with FIGO stage IB-IVA cervical cancer. First-order, shape, and texture features were extracted from the original and filtered images considering 5 different normalizations (four taken from the available literature, and one based on urine ADC) and two different quantization techniques (fixed-bin widths from 0.05 to 25, and fixed-bin count). Stability of radiomic features was assessed using intraclass correlation coefficient (ICC): poor (ICC < 0.75); good (0.75 ICC 0.89), and excellent (ICC ! 0.90). Dependencies of the features with tumor volume were assessed using Spearman's correlation coefficient (q). Results: The approach using urine-normalized values together with a smaller bin width (0.05) was the most reproducible (428/552, 78% features with ICC ! 0.75); the fixed-bin count approach was the least (215/552, 39% with ICC ! 0.75). Without normalization, using a fixed bin width of 25, 348/552 (63%) of features had an ICC ! 0.75. Overall, 26% (range 25-30%) of the features were volume-dependent (q ! 0.6). None of the volume-independent shape features were found to be reproducible. Conclusion: Applying normalization prior to features extraction increases the reproducibility of ADCbased radiomics features. When normalization is applied, a fixed-bin width approach with smaller widths is suggested. Ó 2019 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 143 (2020) 88-94 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Cervical cancer is the fourth most frequent cancer in women, with an estimated 570,000 new cases in 2018, representing 6.6% of all female cancers worldwide. Cervical cancer still represents a significant burden for middle-and low-income countries [1]. Standard treatment for locally advanced (stage IB2-IVA) cervical cancer is concurrent chemoradiation.Computed Tomography (CT) and Magnetic Resonance (MR) are the standard imaging modalities for cervical cancer staging and evaluation of treatment response. Through appropriate choice of pulse sequences MR imaging provides greater soft tissue contrast than CT and enables assessment of physiological parameters and biochemical function. Diffusion-weighted imaging (DWI) in MR enables measurement of water diffusivity via generation of Apparent Diffusion Coefficient (ADC) maps, and ADC is an established biomarker of tumor cell density and related changes posttherapy [2]. DWI is increasing acquired in addition to T2weighted MRI to detect cervical tumor [3], and pre-treatment tumor ADC has been shown to be p...
OBJECTIVES Partial restoration of aortic flow during resuscitative endovascular balloon occlusion of the aorta (REBOA) is advocated by some to mitigate distal ischemia. Our laboratory has validated the mechanics and optimal partial REBOA (pREBOA) flow rates using a prototype device. We hypothesize that pREBOA will increase survival when compared with full REBOA (fREBOA) in prolonged nonoperative management of hemorrhagic shock. METHODS Twenty swine underwent placement of aortic flow probes, zone 1 REBOA placement, and 20% blood volume hemorrhage. They were randomized to either solid organ or abdominal vascular injury. The pREBOA arm (10 swine) underwent full inflation for 10 minutes and then deflation to a flow rate of 0.5 L/min for 2 hours. The fREBOA arm (10 swine) underwent full inflation for 60 minutes, followed by deflation/resuscitation. The primary outcome is survival, and secondary outcomes are serologic/pathologic signs of ischemia-reperfusion injury and quantity of hemorrhage. RESULTS Two of 10 swine survived in the fREBOA group (2/5 solid organ injury; 0/5 abdominal vascular injury), whereas 7 of 10 swine survived in the pREBOA group (3/5 solid organ injury, 4/5 abdominal vascular injury). Survival was increased (p = 0.03) and hemorrhage was higher in the pREBOA group (solid organ injury, 1.36 ± 0.25 kg vs. 0.70 ± 0.33 kg, p = 0.007; 0.86 ± 0.22 kg vs. 0.71 ± 0.28 kg, not significant). Serum evidence of ischemia was greater with fREBOA, but this was not significant (e.g., lactate, 16.91 ± 3.87 mg/dL vs. 12.96 ± 2.48 mg/dL at 120 minutes, not significant). Swine treated with pREBOA that survived demonstrated trends toward lower alanine aminotransferase, lower potassium, and higher calcium. The potassium was significantly lower in survivors at 60 minutes and 90 minutes time points (5.97 ± 0.60 vs. 7.53 ± 0.90, p = 0.011; 6.67 ± 0.66 vs. 8.15 ± 0.78, p = 0.029). Calcium was significantly higher at 30 minutes, 60 minutes, and 90 minutes (8.56 ± 0.66 vs. 7.50 ± 0.40, p = 0.034; 8.63 ± 0.62 vs. 7.15 ± 0.49, p = 0.019; 8.96 ± 0.64 vs. 7.00, p = 0.028). CONCLUSION Prolonged pREBOA at a moderate distal flow rate provided adequate hemorrhage control, improved survival, and had evidence of decreased ischemic injury versus fREBOA. Prophylactic aggressive calcium supplementation may have utility before and during the reperfusion phase.
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