Disruption of a GATA2-TAL1-ERG regulatory circuit promotes erythroid transition in healthy and leukemic stem cells.

Changes in gene regulation and expression govern orderly transitions from hematopoietic stem cells to terminally differentiated blood cell types. These transitions are disrupted during leukemic transformation, but knowledge of the gene regulatory changes underpinning this process is elusive. We hypothesized that identifying core gene regulatory networks in healthy hematopoietic and leukemic cells could provide insights into network alterations that perturb cell state transitions. A heptad of transcription factors (LYL1, TAL1, LMO2, FLI1, ERG, GATA2, and RUNX1) bind key hematopoietic genes in human CD34+ hematopoietic stem and progenitor cells (HSPCs) and have prognostic significance in acute myeloid leukemia (AML). These factors also form a densely interconnected circuit by binding combinatorially at their own, and each other's, regulatory elements. However, their mutual regulation during normal hematopoiesis and in AML cells, and how perturbation of their expression levels influences cell fate decisions remains unclear. In this study, we integrated bulk and single-cell data and found that the fully connected heptad circuit identified in healthy HSPCs persists, with only minor alterations in AML, and that chromatin accessibility at key heptad regulatory elements was predictive of cell identity in both healthy progenitors and leukemic cells. The heptad factors GATA2, TAL1, and ERG formed an integrated subcircuit that regulates stem cell-to-erythroid transition in both healthy and leukemic cells. Components of this triad could be manipulated to facilitate erythroid transition providing a proof of concept that such regulatory circuits can be harnessed to promote specific cell-type transitions and overcome dysregulated hematopoiesis.

Point-of-Care Ultrasound Use to Differentiate Hematoma and Sarcoma of the Thigh in the Pediatric Emergency Department.

Hematomas and soft tissue sarcomas can be difficult to differentiate clinically, even with the addition of traditional imaging modalities. There are several case reports of sarcomas being misdiagnosed as hematomas, most commonly with a history of mild trauma. In this case report, we described a sarcoma initially misinterpreted as a hematoma on ultrasound. Key clinical features and sonographic findings that may assist clinicians using point-of-care ultrasound to correctly differentiate sarcomas from hematomas are reviewed. A soft tissue mass larger than 5 cm, with internal vascular Doppler flow, presenting without a clear mechanism of injury or with constitutional symptoms should be considered as suspicious for malignancy.

Morbidity and mortality outcomes of patients requiring isolated tricuspid valve surgery: a retrospective cohort study of 537 patients in New South Wales between 2002 and 2018.

OBJECTIVES: The aim of the study was to evaluate mortality and morbidity outcomes following open-heart isolated tricuspid valve surgery (TVSx) with medium to long-term follow-up. DESIGN: Retrospective cohort study. SETTING: New South Wales public and private hospital admissions between 1 January 2002 and 30 June 2018. PARTICIPANTS: A total of 537 patients underwent open isolated TVSx during the study period. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was all-cause mortality tracked from the death registry to 31 December 2018. Secondary morbidity outcomes, including admission for congestive cardiac failure (CCF), new atrial fibrillation (AF), infective endocarditis (IE), pulmonary embolism (PE) and insertion of a permanent pacemaker (PPM) or implantable cardioverter-defibrillator (ICD), were tracked from the Admitted Patient Data Collection database. Independent mortality associations were determined using the Cox regression method. RESULTS: A total of 537 patients underwent open isolated TVSx (46% male): median age (IQR) was 63.5 years (43.9-73.8 years) with median length of stay of 16 days (10-31 days). Main cardiovascular comorbidities were AF (54%) and CCF (42%); 67% had rheumatic tricuspid valve. In-hospital and total mortality were 7.4% and 39.3%, respectively (mean follow-up: 4.8 years). Cause-specific deaths were evenly split between cardiovascular and non-cardiovascular causes. Predictors of mortality included a history of CCF (HR=1.78, 95% CI 1.33 to 2.38, p<0.001) and chronic pulmonary disease (HR=2.66, 95% CI 1.63 to 4.33, p<0.001). In-hospital PPM rate was 10.0%. At 180 days, 53 (9.9%) patients were admitted for CCF, 25 (10.1%) had new AF, 7 (1.5%) had new IE and <1% had PE, post-discharge PPM or ICD insertion. CONCLUSION: Open isolated TVSx carries significant mortality risk, with decompensated CCF and new AF the most common morbidities encountered after surgery. This report forms a benchmark to compare outcomes with newer percutaneous tricuspid interventions.

Distinguishing Features of Adolescents With Undiagnosed Infectious Tuberculosis Attending a Pediatric Emergency Department.

More than 10 days of fever or 13 days of cough differentiated adolescent patients presenting to a pediatric emergency department with infectious tuberculosis (TB) from most patients with pneumonia. Upper lobe involvement was significantly more common in patients with TB. Symptom- and radiograph-based algorithms could minimize TB exposure and aid diagnosis.

Long-term changes in ground water chemistry at a phytoremediation demonstration site.

A field-scale demonstration project was conducted to evaluate the capability of eastern cottonwood trees (Populus deltoides) to attenuate trichloroethene (TCE) contamination of ground water. By the middle of the sixth growing season, trees planted where depth to water was <3 m delivered enough dissolved organic carbon to the underlying aquifer to lower dissolved oxygen concentrations, to create iron-reducing conditions along the plume centerline and sulfate-reducing or methanogenic conditions in localized areas, and to initiate in situ reductive dechlorination of TCE. Apparent biodegradation rate constants for TCE along the centerline of the plume beneath the phytoremediation system increased from 0.0002/d to 0.02/d during the first six growing seasons. The corresponding increase in natural attenuation capacity of the aquifer along the plume centerline, from 0.0004/m to 0.024/m, is associated with a potential decrease in plume-stabilization distance from 9680 to 160 m. Demonstration results provide insight into the amount of vegetation and time that may be needed to achieve cleanup objectives at the field scale.

Patient-controlled ropivacaine analgesia after arthroscopic subacromial decompression.

PURPOSE: To evaluate the efficacy of a subacromial patient-controlled analgesia (PCA) infusion of 0.2% ropivacaine versus saline for postoperative pain control following arthroscopic shoulder surgery. TYPE OF STUDY: Double-blind prospective randomized study. METHODS: A prospective, randomized double-blind study was performed on a consecutive group of 24 patients. All patients had arthroscopic subacromial decompression. Ropivacaine was chosen as the study drug due to the association of cardiac toxicity with the use of bupivacaine. The surgeon, anesthesiologist, and the operating room staff were blinded to the randomization. Immediately before surgery, the pharmacy staff randomized the type of drug infusion. Patients were asked to record their pain score using a visual analog scale (VAS) along with the amount of hydrocodone consumption for the first 2 days after surgery. RESULTS: Nineteen patients completed the study. Ten patients received a subacromial infusion of 0.2% ropivacaine at 5 mL per hour with a bolus dose of 2 mL at a 15-minute lockout period via a microjet PCA pump (group I). Nine patients received saline in the same experimental conditions (group II). The use of a PCA ropivacaine infusion (group I) resulted in a significant reduction of postoperative pain by 34% as measured by VAS scale (P <.05), but no changes in the amount of hydrocodone consumption. CONCLUSIONS: The use of subacromial 0.2% ropivacaine PCA infusion provided effective postoperative pain control. LEVEL OF EVIDENCE: Level I.

Determination of the relative uptake of ground vs. surface water by Populus deltoides during phytoremediation.

The use of plants to remediate polluted groundwater is becoming an attractive alternative to more expensive traditional techniques. In order to adequately assess the effectiveness of the phytoremediation treatment, a clear understanding of water-use habits by the selected plant species is essential. We examined the relative uptake of surface water (i.e., precipitation) vs. groundwater by mature Populus deltoides by applying irrigation water at a rate equivalent to a 5-cm rain event. We used stable isotopes of hydrogen (D) and oxygen (18O) to identify groundwater and surface water (irrigation water) in the xylem sap water. Pretreatment isotopic ratios of both deuterium and 18O, ranked from heaviest to lightest, were irrigation water > groundwater > xylem sap. The discrepancy in preirrigation isotopic signatures between groundwater and xylem sap suggests that in the absence of a surface source of water (i.e., between rain events) there is an unknown amount of water being extracted from sources other than groundwater (i.e., soil surface water). We examined changes in volumetric soil water content (%), total hourly sapflux rates, and trichloroethene (TCE) concentrations. Following the irrigation treatment, volumetric soil water increased by 86% and sapflux increased by as much as 61%. Isotopic signatures of the xylem sap became substantially heavier following irrigation, suggesting that the applied irrigation water was quickly taken up by the plants. TCE concentrations in the xylem sap were diluted by an average of 21% following irrigation; however, dilution was low relative to the increase in sapflux. Our results show that water use by Populus deltoides is variable. Hence, studies addressing phytoremediation effectiveness must account for the relative proportion of surface vs. groundwater uptake.