Ethylene-mediated nitric oxide depletion pre-adapts plants to hypoxia stress

Timely perception of adverse environmental changes is critical for survival. Dynamic changes in gases are important cues for plants to sense environmental perturbations, such as submergence. In Arabidopsis thaliana, changes in oxygen and nitric oxide (NO) control the stability of ERFVII transcription factors. ERFVII proteolysis is regulated by the N-degron pathway and mediates adaptation to flooding-induced hypoxia. However, how plants detect and transduce early submergence signals remains elusive. Here we show that plants can rapidly detect submergence through passive ethylene entrapment and use this signal to pre-adapt to impending hypoxia. Ethylene can enhance ERFVII stability prior to hypoxia by increasing the NO-scavenger PHYTOGLOBIN1. This ethylene-mediated NO depletion and consequent ERFVII accumulation pre-adapts plants to survive subsequent hypoxia. Our results reveal the biological link between three gaseous signals for the regulation of flooding survival and identifies key regulatory targets for early stress perception that could be pivotal for developing flood-tolerant crops

Tubal flushing with oil-based or water-based contrast at hysterosalpingography for infertility:long-term reproductive outcomes of a randomized trial

Objective: To determine the impact of oil -based versus water -based contrast on pregnancy and live birth rates <5 years after hysterosalpingography (HSG) in infertile women. Design: A 5 -year follow-up study of a multicenter randomized trial. Setting: Hospitals. Patient(s): Infertile women with an ovulatory cycle, 18 - 39 years of age, and having a low risk of tubal pathology. Intervention(s): Use of oil -based versus water -based contrast during HSG. Main Outcome Measure(s): Ongoing pregnancy, live births, time to ongoing pregnancy, second ongoing pregnancy. Result(s): A total of 1,119 women were randomly assigned to HSG with oil -based contrast (n = 557) or water -based contrast (n = 562). After 5 years, 444 of 555 women in the oil group (80.0%) and 419 of 559 women in the water group (75.0%) had an ongoing pregnancy (relative risk [RR] 1.07; 95% con fi dence interval [CI] 1.00 - 1.14), and 415 of 555 women in the oil group (74.8%) and 376 of 559 women in the water group (67.3%) had live births (RR 1.11; 95% CI 1.03 - 1.20). In the oil group, 228 pregnancies (41.1%) were conceived naturally versus 194 (34.7%) pregnancies in the water group (RR 1.18; 95% CI 1.02 - 1.38). The time to ongoing pregnancy was signi fi cantly shorter in the oil group versus the water group (10.0 vs. 13.7 months; hazard ratio, 1.25; 95% CI 1.09 - 1.43). No difference was found in the occurrence of a second ongoing pregnancy. Conclusion(s): During a 5 -year time frame, ongoing pregnancy and live birth rates are higher after tubal fl ushing with oil -based contrast during HSG compared with water -based contrast. More pregnancies are naturally conceived and time to ongoing pregnancy is shorter after HSG with oil -based contrast. Clinical Trial Registration Number: Netherlands Trial Register (NTR) 3270 and NTR6577(www.trialregister.nl). (Fertil Steril (R) 2020;114:155-62. (C) 2020 by American Society for Reproductive Medicine.

Immunophenotypic Analysis of Acute Megakaryoblastic Leukemia: A EuroFlow Study

Acute megakaryoblastic leukemia (AMKL) is a rare and heterogeneous subtype of acute myeloid leukemia (AML). We evaluated the immunophenotypic profile of 72 AMKL and 114 non-AMKL AML patients using the EuroFlow AML panel. Univariate and multivariate/multidimensional analyses were performed to identify most relevant markers contributing to the diagnosis of AMKL. AMKL patients were subdivided into transient abnormal myelopoiesis (TAM), myeloid leukemia associated with Down syndrome (ML-DS), AML—not otherwise specified with megakaryocytic differentiation (NOS-AMKL), and AMKL—other patients (AML patients with other WHO classification but with flowcytometric features of megakaryocytic differentiation). Flowcytometric analysis showed good discrimination between AMKL and non-AMKL patients based on differential expression of, in particular, CD42a.CD61, CD41, CD42b, HLADR, CD15 and CD13. Combining CD42a.CD61 (positive) and CD13 (negative) resulted in a sensitivity of 71% and a specificity of 99%. Within AMKL patients, TAM and ML-DS patients showed higher frequencies of immature CD34+/CD117+ leukemic cells as compared to NOS-AMKL and AMKL-Other patients. In addition, ML-DS patients showed a significantly higher expression of CD33, CD11b, CD38 and CD7 as compared to the other three subgroups, allowing for good distinction of these patients. Overall, our data show that the EuroFlow AML panel allows for straightforward diagnosis of AMKL and that ML-DS is associated with a unique immunophenotypic profile.The EuroFlow Consortium received support from the FP6-2004-LIFESCIHEALTH-5 program of the European Commission (grant LSHB-CT-2006-018708) as Specific Targeted Research Project (STREP). The EuroFlow Consortium is part of the European Scientific Foundation for HematoOncology (ESLHO), a Scientific Working Group (SWG) of the European Hematology Association (EHA). The work of C.E.P. and E.S.C. was partially supported by FAPERJ (Grant E26/200.840/2021- CNE; E26/210.379/2018 and E26/110.105/2014); CAPES-PROEX; and CNPq (Grant 306258/2019-6 and 303765/2018-6). M.N. and E.M. were supported by the Ministry of Health of the Czech Republic, grant number NU20J-07-00028. S.M. was supported by Acción Estratégica en Salud (AES) (Grant PI21_01115) and the grant of CIBERONC of the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Madrid, Spain and FONDOS FEDER (no. CB16/12/00400)

Ethylene Differentially Modulates Hypoxia Responses and Tolerance across Solanum Species

The increasing occurrence of floods hinders agricultural crop production and threatens global food security. The majority of vegetable crops are highly sensitive to flooding and it is unclear how these plants use flooding signals to acclimate to impending oxygen deprivation (hypoxia). Previous research has shown that the early flooding signal ethylene augments hypoxia responses and improves survival in Arabidopsis. To unravel how cultivated and wild Solanum species integrate ethylene signaling to control subsequent hypoxia acclimation, we studied the transcript levels of a selection of marker genes, whose upregulation is indicative of ethylene-mediated hypoxia acclimation in Arabidopsis. Our results suggest that ethylene-mediated hypoxia acclimation is conserved in both shoots and roots of the wild Solanum species bittersweet (Solanum dulcamara) and a waterlogging-tolerant potato (Solanum tuberosum) cultivar. However, ethylene did not enhance the transcriptional hypoxia response in roots of a waterlogging-sensitive potato cultivar, suggesting that waterlogging tolerance in potato could depend on ethylene-controlled hypoxia responses in the roots. Finally, we show that ethylene rarely enhances hypoxia-adaptive genes and does not improve hypoxia survival in tomato (Solanum lycopersicum). We conclude that analyzing genes indicative of ethylene-mediated hypoxia acclimation is a promising approach to identifying key signaling cascades that confer flooding tolerance in crops

Ethylene Differentially Modulates Hypoxia Responses and Tolerance across Solanum Species

The increasing occurrence of floods hinders agricultural crop production and threatens global food security. The majority of vegetable crops are highly sensitive to flooding and it is unclear how these plants use flooding signals to acclimate to impending oxygen deprivation (hypoxia). Previous research has shown that the early flooding signal ethylene augments hypoxia responses and improves survival in Arabidopsis. To unravel how cultivated and wild Solanum species integrate ethylene signaling to control subsequent hypoxia acclimation, we studied the transcript levels of a selection of marker genes, whose upregulation is indicative of ethylene-mediated hypoxia acclimation in Arabidopsis. Our results suggest that ethylene-mediated hypoxia acclimation is conserved in both shoots and roots of the wild Solanum species bittersweet (Solanum dulcamara) and a waterlogging-tolerant potato (Solanum tuberosum) cultivar. However, ethylene did not enhance the transcriptional hypoxia response in roots of a waterlogging-sensitive potato cultivar, suggesting that waterlogging tolerance in potato could depend on ethylene-controlled hypoxia responses in the roots. Finally, we show that ethylene rarely enhances hypoxia-adaptive genes and does not improve hypoxia survival in tomato (Solanum lycopersicum). We conclude that analyzing genes indicative of ethylene-mediated hypoxia acclimation is a promising approach to identifying key signaling cascades that confer flooding tolerance in crops

How do the costs of physical therapy and arthroscopic partial meniscectomy compare?: A trial-based economic evaluation of two treatments in patients with meniscal tears alongside the ESCAPE study

OBJECTIVES: To examine whether physical therapy (PT) is cost-effective compared with arthroscopic partial meniscectomy (APM) in patients with a non-obstructive meniscal tear, we performed a full trial-based economic evaluation from a societal perspective. In a secondary analysis-this paper-we examined whether PT is non-inferior to APM. METHODS: We recruited patients aged 45-70 years with a non-obstructive meniscal tear in nine Dutch hospitals. Resource use was measured using web-based questionnaires. Measures of effectiveness included knee function using the International Knee Documentation Committee (IKDC) and quality-adjusted life-years (QALYs). Follow-up was 24 months. Uncertainty was assessed using bootstrapping techniques. The non-inferiority margins for societal costs, the IKDC and QALYs, were €670, 8 points and 0.057 points, respectively. RESULTS: We randomly assigned 321 patients to PT (n=162) or APM (n=159). PT was associated with significantly lower costs after 24 months compared with APM (-€1803; 95% CI -€3008 to -€838). The probability of PT being cost-effective compared with APM was 1.00 at a willingness to pay of €0/unit of effect for the IKDC (knee function) and QALYs (quality of life) and decreased with increasing values of willingness to pay. The probability that PT is non-inferior to APM was 0.97 for all non-inferiority margins for the IKDC and 0.89 for QALYs. CONCLUSIONS: The probability of PT being cost-effective compared with APM was relatively high at reasonable values of willingness to pay for the IKDC and QALYs. Also, PT had a relatively high probability of being non-inferior to APM for both outcomes. This warrants further deimplementation of APM in patients with non-obstructive meniscal tears. TRIAL REGISTRATION NUMBERS: NCT01850719 and NTR3908

Posterolateral or direct lateral approach for cemented hemiarthroplasty after femoral neck fracture (APOLLO):protocol for a multicenter randomized controlled trial with economic evaluation and natural experiment alongside

BACKGROUND AND PURPOSE: The posterolateral and direct lateral surgical approach are the 2 most common surgical approaches for performing a hemiarthroplasty in patients with a hip fracture. It is unknown which surgical approach is preferable in terms of (cost-)effectiveness and quality of life. METHODS AND ANALYSIS: We designed a multicenter randomized controlled trial (RCT) with an economic evaluation and a natural experiment (NE) alongside. We will include 555 patients ≥ 18 years with an acute femoral neck fracture. The primary outcome is patient-reported health-related quality of life assessed with the EQ-5D-5L. Secondary outcomes include healthcare costs, complications, mortality, and balance (including fear of falling, actual falls, and injuries due to falling). An economic evaluation will be performed for quality adjusted life years (QALYs). We will use variable block randomization stratified for hospital. For continuous outcomes, we will use linear mixed-model analysis. Dichotomous secondary outcome measures will be analyzed using chi-square statistics and logistic regression models. Primary analyses are based on the intention-to-treat principle. Additional as treated analyses will be performed to evaluate the effect of protocol deviations. Study summary: (i) Largest RCT addressing the health-related patient outcome of the main surgical approaches of hemiarthroplasty. (ii) Focus on outcomes that are important for the patient. (iii) Pragmatic and inclusive RCT with few exclusion criteria, e.g., patients with dementia can participate. (iv) Natural experiment alongside to amplify the generalizability. (v) The first study conducting a costutility analysis comparing both surgical approaches

Adherence and acceptability of a robot-assisted Pivotal Response Treatment protocol for children with autism spectrum disorder

The aim of this study is to present a robot-assisted therapy protocol for children with ASD based on the current state-of-the-art in both ASD intervention research and robotics research, and critically evaluate its adherence and acceptability based on child as well as parent ratings. The robot-assisted therapy was designed based on motivational components of Pivotal Response Treatment (PRT), a highly promising and feasible intervention focused at training “pivotal” (key) areas such as motivation for social interaction and self-initiations, with the goal of establishing collateral gains in untargeted areas of functioning and development, affected by autism spectrum disorders. Overall, children (3–8 y) could adhere to the robot-assisted therapy protocol (Mean percentage of treatment adherence 85.5%), showed positive affect ratings after therapy sessions (positive in 86.6% of sessions) and high robot likability scores (high in 79.4% of sessions). Positive likability ratings were mainly given by school-aged children (H(1) = 7.91, p =.005) and related to the movements, speech and game scenarios of the robot. Parent ratings on the added value of the robot were mainly positive (Mean of 84.8 on 0–100 scale), while lower parent ratings were related to inflexibility of robot behaviour