Terpottosen0876

The ADC synergizes with fludarabine, making it a natural combination to use in a minimal toxicity conditioning regimen. Our ADC prolongs the survival of mice engrafted with human cell lines and depletes primary human AML engrafted with a single injection. In a humanized mouse model, a single injection of the ADC depletes CD34+ HSPCs and CD34+CD38-CD90+ hematopoietic stem cells. This work establishes an anti-CD300f ADC as an attractive potential therapeutic that, if validated in transplant models using a larger cohort of primary AML samples, will reduce relapse rate and toxicity for patients with AML undergoing allo-HSCT. © 2020 by The American Society of Hematology.BACKGROUND The Standardized Antimicrobial Administration Ratio (SAAR) is a risk-adjusted metric of antimicrobial use (AU) developed by the CDC in 2015 as a tool for hospital antimicrobial stewardship programs (ASPs) to track and compare AU to a national benchmark. In 2018, CDC updated the SAAR by expanding the locations and antimicrobial categories for which SAARs can be calculated and by modeling adult and pediatric locations separately. METHODS We identified eligible patient care locations and defined SAAR antimicrobial categories. Predictive models were developed for eligible adult and pediatric patient care locations using negative binomial regression applied to nationally aggregated AU data from locations reporting ≥9 months of 2017 data to the National Healthcare Safety Network (NHSN). RESULTS 2017 baseline SAAR models were developed for seven adult and eight pediatric SAAR antimicrobial categories using data reported from 2,156 adult and 170 pediatric locations across 457 hospitals. The inclusion of step-down units and general hematology-oncology units in adult 2017 baseline SAAR models and the addition of SAARs for narrow-spectrum beta-lactam agents, antifungals predominantly used for invasive candidiasis, antibacterial agents posing the highest risk for Clostridioides difficile infection, and azithromycin (pediatrics only) expand the role SAARs can play in ASP efforts. Final risk-adjusted models are used to calculate predicted antimicrobial days, the denominator of the SAAR, for 40 SAAR types displayed in NHSN. CONCLUSIONS SAARs can be used as a metric to prompt investigation into potential overuse or underuse of antimicrobials and to evaluate the effectiveness of ASP interventions. Published by Oxford University Press for the Infectious Diseases Society of America 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.BACKGROUND Hypertension is a common comorbidity associated with chronic kidney disease (CKD). Treatment in these patients often involves L-type Ca2+ channel (LTCC) blockers. The effect of chronic LTCC-blockade treatment on resistance vasculature was investigated in a genetic hypertensive rat model of CKD, the Lewis Polycystic Kidney (LPK) rat. METHODS Mixed-sex LPK and Lewis control rats (total n=38) were allocated to treated (amlodipine 20mg/kg/day p.o. from 4-18 weeks) and vehicle groups. Following systolic blood pressure and renal function assessment, animals were euthanized and mesenteric vasculature was collected for functional and structural assessment using pressure myography and histology. RESULTS Amlodipine treatment reduced LPK rat blood pressure (untreated vs. treated 185±5 vs. 165±9 mmHg; P=0.019), reduced plasma creatinine (untreated vs. treated 197±17 vs. 140±16 µmol/L; P=0.002), and improved some vascular structural parameters (internal and external diameters, and wall-lumen ratios); however wall thickness was still increased in LPK relative to Lewis despite treatment (Lewis vs. LPK 31±2 vs. 41±2 µm, P=0.047). Treatment improved LPK rats' endothelium dysfunction, and nitric oxide-dependent and endothelium-derived hyperpolarization-dependent vasorelaxation components, and downregulated prostanoid contributions. LTCC blockade had no effect on biomechanical properties of compliance and intrinsic stiffness, nor artery wall composition. CONCLUSIONS Our results indicate that blockade of LTCCs with amlodipine is effective in improving, to a certain extent, detrimental structural and functional vascular features of resistance arteries in CKD. © American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email journals.permissions@oup.com.BACKGROUND Autologous fat graft is often employed to treat body contour defects. There is currently increased interest in the regenerative properties of fat grafting. OBJECTIVES The authors evaluated the histological changes of fat grafting in a blinded randomized controlled trial of staged fat grafting-abdominoplasty. METHODS Ten women between 24 and 55 years of age with a body mass index less then 30 kg/m2 and previous cesarean scar were submitted to fat grafting followed by staged abdominoplasty. The C-section scar served as a landmark for standardization of fat grafting site and control. One side of the abdomen was fat grafted and the other was left intact (control). At the time of abdominoplasty, 4 months later, a full-thickness skin sample from each hemi abdomen (fat-grafted area and control) was collected and sent to histological analysis. RESULTS All of the fat-grafted samples showed extracellular lipids and signs of fat graft viability, whereas no such changes occurred in the control group. There were no statistically significant differences in fat-grafted vs control samples regarding skin inflammatory infiltrate (P = 0.582), dermis thickness (P = 0.973), vascular density (P = 0.326), and amount of elastic fibers (P = 1). CONCLUSIONS The histological evaluation of women's abdominoplasty surgical site skin after 4 months of fat grafting showed signs of fat graft in 100% of the grafted sides but no change in skin inflammatory infiltrate, dermis thickness, vascularity density, or elastic fiber quantity. © 2020 The Aesthetic Society. Reprints and permission journals.permissions@oup.com.Objective ：We investigated the relationship between salivary cortisol level and the prevalence of depression 585 police officers working at the Police Departments of Beijing. METHOD Cross-sectional data were obtained from 585 Chinese police officers recruited from Beijing, China. Salivary cortisol was assayed using the chemiluminescence immunoassay. A multiple logistic regression analysis adjusted for potential confounders was used to assess independent associations between salivary cortisol level and depression. RESULTS The median age of the included was 38 years (IQR, 29-45), 20.9% were female (n=122). Finally, 15.6% (91/585; 95% CI 12.6%-18.5%) were considered to have depression. The median salivary cortisol level was significantly higher in police with depression than those police without depression [14.5(IQR, 11.9-15.9) nmol/l vs. 11.8(IQR, 9.4-14.2) nmol/l; P less then 0.001]. The depression distribution across the salivary cortisol quartiles ranged between 5.4% (first quartile) to 26.9% (fourth quartile), P for trend. CONCLUSIONS The data showed that elevated levels of salivary cortisol were associated with increased prevalence of depression. Copyright 2020 The Author(s).AIMS  Data on patient characteristics, prevalence, and outcomes of atrial fibrillation (AF) patients without traditional risk factors, often labelled 'lone AF', are sparse. METHODS AND RESULTS The RE-LY AF registry included 15 400 individuals who presented to emergency departments with AF in 47 countries. This analysis focused on patients without traditional risk factors, including age ≥60 years, hypertension, coronary artery disease, heart failure, left ventricular hypertrophy, congenital heart disease, pulmonary disease, valve heart disease, hyperthyroidism, and prior cardiac surgery. Patients without traditional risk factors were compared with age- and region-matched controls with traditional risk factors (13 fashion). In 796 (5%) patients, no traditional risk factors were present. However, 98% (779/796) had less-established or borderline risk factors, including borderline hypertension (130-140/80-90 mmHg; 47%), chronic kidney disease (eGFR 14 units/week; 4%), and smoking (25%). Compared with patients with traditional risk factors (n = 2388), patients without traditional risk factors were more often men (74% vs. 59%, P  less then  0.001) had paroxysmal AF (55% vs. 37%, P  less then  0.001) and less AF persistence after 1 year (21% vs. 49%, P  less then  0.001). Furthermore, 1-year stroke occurrence rate (0.6% vs. 2.0%, P = 0.013) and heart failure hospitalizations (0.9% vs. 12.5%, P  less then  0.001) were lower. However, risk of AF-related re-hospitalization was similar (18% vs. 21%, P = 0.09). CONCLUSION Almost all patients without traditionally defined AF risk factors have less-established or borderline risk factors. These patients have a favourable 1-year prognosis, but risk of AF-related re-hospitalization remains high. Greater emphasis should be placed on recognition and management of less-established or borderline risk factors. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email journals.permissions@oup.com.OBJECTIVES This paper asks how the educational attainments of multiple family members, including parents and offspring, are associated with the cognitive health of older adults in the United States. METHODS We use panel data from the U.S. Health and Retirement Study (2000-2012) to examine how the education of an individual, their parent(s), and their offspring are associated with the prevalence of moderate/severe cognitive impairment and the onset of cognitive impairment among older adults using logistic regression and discrete-time event history analysis, respectively. RESULTS We found that when combined, only the education of the individual is inversely associated with cognitive impairment at baseline. However, both the educational attainments of an individual and their offspring are negatively associated with the risk of becoming cognitively impaired, among individuals who were not already cognitively impaired. Conversely, parental education was not predictive of being cognitively impaired or the onset of impairment. Furthermore, we found that respondent gender did not moderate the relationship between a family member's education and respondent cognitive health. DISCUSSION This study adds to current research by asking how resources from earlier and subsequent generations matter for older adults' cognitive health. Although we found little evidence that parental education matters at this life stage, results suggest that offspring education has a salient positive effect on later-lifer cognitive health. This finding underscores an overlooked source of health disparities - offspring resources - and highlights how a family perspective remains a powerful tool for understanding health inequalities in later life. Published by Oxford University Press on behalf of The Gerontological Society of America 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.Resources for clinical research are limited. With increasing demand for patient-centred care, which is growing into an integral component of modern medicine, studying outcomes of patients with specific clinical characteristics is becoming increasingly important. Given the high cost of clinical trials and the time it takes to complete an investigation, it has become compulsory for investigators to assess not only treatment effects between the main randomized groups but also to try to identify clinically relevant subgroups that may particularly benefit from specific treatments. Publications of subgroup analyses turned out to be prevalent, and more importantly, these findings play a significant role in strategic planning and decision-making processes. find protocol Therefore, raising awareness among clinicians about the concepts and values of subgroup analysis is an aspect of improving patient outcomes. In this statistical primer, we give a broad introduction to the topic of subgroup analysis in scientific research. We furthermore discuss the concept of subgroup analysis; the motivation for assessing subgroups; the types of subgroup analyses and the paradigm of hypothesis-generating research; the proper statistical methods for the examination of subgroup effects; and the optimal approach for interpretation of results.