Woodssvane5976

BACKGROUND Diagnosis of schistosomiasis remains elusive soon after infection. We evaluated several diagnostic methods in a cluster of travelers simultaneously exposed to freshwater in South Africa. METHODS Eosinophil count, schistosome antibody tests, stool and urine microscopy, and serum Dra1 PCR assays were performed at week 4-5 (w4-5, early symptomatic phase), week 7-8 (w7-8, praziquantel treatment), and week 12-14 (w12-14, post-treatment). Sequencing was done on serum of 3 patients to identify the species. RESULTS Of the 34 travelers (16 adults, 18 children), 32 developed symptoms 2 to 6 weeks after exposure. A raised eosinophil count (>750/µL) count was seen in 12/33 at w4-5, and in 22/34 at w7-8. Schistosoma antibodies were detected in 3/33 at w4-5, in 12/34 at w7-8 and w12-14. The Dra1 PCR was positive in 24/33 travelers at w4-5, in 31/34 at w7-8, in 25/34 at w12-14, and at least once in all. Ova were absent in all urine and fecal samples obtained. Sequencing identified S. mattheei nuclear and S. haematobium mitochondrial DNA, indicative of a hybrid species. CONCLUSION The Dra-1 PCR confirmed diagnosis in all exposed travelers at a much earlier stage than conventional tests. The causative species is probably a S. mattheei x S. haematobium hybrid. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly reduces the rate of relapse in acute myeloid leukemia (AML) but comes at the cost of significant treatment-related mortality. Despite the reduction in relapse overall, it remains common, especially in high-risk groups. The outcomes for patients who relapse after transplant remains very poor. A large proportion of the morbidity that prevents most patients from accessing allo-HSCT is due to toxic nonspecific conditioning agents that are required to remove recipient hematopoietic stem and progenitor cells (HSPCs), allowing for successful donor engraftment. CD300f is expressed evenly across HSPC subtypes. CD300f has transcription and protein expression equivalent to CD33 on AML. We have developed an anti-CD300f antibody that efficiently internalizes into target cells. We have generated a highly potent anti-CD300f antibody-drug conjugate (ADC) with a pyrrolobenzodiazepine warhead that selectively depletes AML cell lines and colony forming units in vitro. 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. Selleck L-α-Phosphatidylcholine 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.