Pirtobrutinib is a highly selective, non-covalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). Patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) were treated with fixed-duration pirtobrutinib plus venetoclax (PV) or pirtobrutinib plus venetoclax and rituximab (PVR) in this phase 1b trial (NCT03740529). Prior covalent BTKi therapy was allowed, but not prior venetoclax. Patients were assigned to receive PV (n=15) or PVR (n=10) for 25 cycles. Median age was 66 years (range, 39-78). Median prior lines of therapy was 2 (range, 1-4), and 17 (68%) patients had received prior covalent BTKi. At the data-cutoff date (May 5, 2023), median time on study was 27.0 months for PV and 23.3 months for PVR. Overall response rates were 93.3% (95% CI:68.1-99.8%) for PV and 100% (95% CI:69.2-100.0%) for PVR, with 10 complete responses (PV:7; PVR:3). After 12 cycles of treatment, 85.7% (95% CI:57.2-98.2%) of PV and 90.0% (95% CI:55.5-99.7%) of PVR patients achieved undetectable minimal residual disease assessed in peripheral blood by clonoSEQ® assay at a sensitivity of <1x10-4. Progression-free survival at 18 months was 92.9% (95% CI: 59.1-99.0) for PV patients and 80.0% (95% CI: 40.9-94.6) for PVR patients. No DLTs were observed in either treatment combination during the 5-week assessment period. The most common grade ≥3 adverse events for all patients included neutropenia (52%) and anemia (16%). Adverse events led to dose reduction in 3 patients and discontinuation in 2. In conclusion, fixed-duration PV or PVR was well tolerated and had promising efficacy in patients with R/R CLL, including patients previously treated with a covalent BTKi.
Objectives: To determine the functional domains and symptom scales that affect patients most following radical cystectomy (RC) and urinary diversion (UD), and if a single instrument (or combination) adequately captures these bothersome symptoms. It is unclear whether current patient reported outcome (PRO) instruments that have been used to assess quality of life in patients following RC and UD adequately cover the most bothersome symptoms affecting patients. Materials and methods: A systematic search of MEDLINE, EMBASE, PubMed, Cinahl and Cochrane was conducted from January 2000 to May 2023 for original articles of patients who had RC and UD since 2000 for muscle invasive bladder cancer. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) process was followed. Extracted data included the PRO measures used, domains reported and scores in the first 12 months post-surgery (short-term) and after 12 months (long-term). A conservative threshold of <70 for functional domains and >30 for symptom domains was used to determine which PRO domains were potentially concerning to patients in each study. Quality assessment was performed using the QUALSYST appraisal tool. Results: Thirty-five studies met the inclusion criteria, including a total of eight unique PRO instruments. The main findings indicated that physical function was the most concerning PRO for patients with both neobladder (NB) and ileal conduit (IC) in the short and long term. Additionally, bowel, urinary and sexual bother were concerning symptoms for patients with NB in the long-term, but only in the short-term for those with IC. Conclusions: The main issues are adequately addressed using the combination of EORTC QLQ-C30 and QLQ-BLM30 instruments.
Plants share their habitats with a multitude of different microbes. This close vicinity promoted the evolution of interorganismic interactions between plants and many different microorganisms that provide mutual growth benefits both to the plant and the microbial partner. The symbiosis of Arabidopsis thaliana with the beneficial root colonizing endophyte Serendipita indica represents a well-studied system. Colonization of Arabidopsis roots with S. indica promotes plant growth and stress tolerance of the host plant. However, until now, the molecular mechanism by which S. indica reprograms plant growth remains largely unknown. This study used comprehensive transcriptomics, metabolomics, reverse genetics, and life cell imaging to reveal the intricacies of auxin-related processes that affect root growth in the symbiosis between A. thaliana and S. indica. Our experiments revealed the sustained stimulation of auxin signalling in fungus infected Arabidopsis roots and disclosed the essential role of tightly controlled auxin conjugation in the plant-fungus interaction. It particularly highlighted the importance of two GRETCHEN HAGEN 3 (GH3) genes, GH3.5 and GH3.17, for the fungus infection-triggered stimulation of biomass production, thus broadening our knowledge about the function of GH3s in plants. Furthermore, we provide evidence for the transcriptional alteration of the PIN2 auxin transporter gene in roots of Arabidopsis seedlings infected with S. indica and demonstrate that this transcriptional adjustment affects auxin signalling in roots, which results in increased plant growth.
PURPOSE: Robot-assisted radical cystectomy (RARC) has gained traction in the management of muscle invasive bladder cancer. Urinary diversion for RARC was achieved with orthotopic neobladder and ileal conduit. Evidence on the optimal method of urinary diversion was limited. Long-term outcomes were not reported before. This study was designed to compare the perioperative and oncological outcomes of ileal conduit versus orthotopic neobladder cases of nonmetastatic bladder cancer treated with RARC. PATIENTS AND METHODS: The Asian RARC consortium was a multicenter registry involving nine Asian centers. Consecutive patients receiving RARC were included. Cases were divided into the ileal conduit and neobladder groups. Background characteristics, operative details, perioperative outcomes, recurrence information, and survival outcomes were reviewed and compared. Primary outcomes include disease-free and overall survival. Secondary outcomes were perioperative results. Multivariate regression analyses were performed. RESULTS: From 2007 to 2020, 521 patients who underwent radical cystectomy were analyzed. Overall, 314 (60.3%) had ileal conduit and 207 (39.7%) had neobladder. The use of neobladder was found to be protective in terms of disease-free survival [Hazard ratio (HR) = 0.870, p = 0.037] and overall survival (HR = 0.670, p = 0.044) compared with ileal conduit. The difference became statistically nonsignificant after being adjusted in multivariate cox-regression analysis. Moreover, neobladder reconstruction was not associated with increased blood loss, nor additional risk of major complications. CONCLUSIONS: Orthotopic neobladder urinary diversion is not inferior to ileal conduit in terms of perioperative safety profile and long-term oncological outcomes. Further prospective studies are warranted for further investigation.
Background: Maharishi Amrit Kalash (MAK) 4 and 5 are Ayurvedic herbal nutritional supplements that are believed to have beneficial effects on overall health and wellbeing. This study aimed to systematically review all available randomized controlled trials (RCTs) investigating the clinical effects and safety of MAK. Methods: We included RCTs on therapy, health promotion, and prevention for patients and healthy volunteers of all ages. We systematically searched MEDLINE (via PubMed), EMBASE (via Ovid), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), DHARA, Clinicaltrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform, and Google Scholar from inception through 7 May 2023, with no time or language restrictions. The risk of bias was assessed using the Cochrane Risk of Bias Tool version 1. The protocol was registered with PROSPERO before conducting the review (CRD42023421655). Results: Three RCTs with 418 study participants were included. Two studies were on breast cancer patients and one on healthy adults. The two studies on cancer evaluated the efficacy of MAK in reducing the side effects of chemotherapy in women with breast cancer. The study on healthy adults evaluated whether MAK has an effect on an age-related alertness task as an indicator of cognitive aging. Both studies on breast cancer patients found beneficial effects on performance status, anorexia, vomiting, and body weight. One study reported positive effects regarding stomatitis. Regarding visual alertness, results showed that individuals who received MAK improved in performance. None of the three included studies reported adverse events. The risk of bias was mixed. Due to the small number and heterogeneity of the RCTs, no meta-analysis could be performed. Conclusion: There is evidence that MAK may have supportive effects in chemotherapeutic treatments for breast cancer patients and for healthy individuals regarding visual discrimination. However, it is difficult to verify treatment effects due to the small number of RCTs and the mixed risk of bias. Furthermore, none of the included studies recorded adverse events. Therefore, further high-quality studies are warranted to confirm the potential health benefits of MAK and to determine its optimal dosage and duration of use. Systematic review registration: PROSPERO, CRD42023421655.
BACKGROUND: Preclinical studies have demonstrated that VT1021, a first-in-class therapeutic agent, inhibits tumor growth via stimulation of thrombospondin-1 (TSP-1) and reprograms the tumor microenvironment. We recently reported data from the dose escalation part of a phase I study of VT1021 in solid tumors. Here, we report findings from the dose expansion phase of the same study. METHODS: We analyzed the safety and tolerability, clinical response, and biomarker profile of VT1021 in the expansion portion of the phase I study (NCT03364400). Safety/tolerability is determined by adverse events related to the treatment. Clinical response is determined by RECIST v1.1 and iRECIST. Biomarkers are measured by multiplexed ion beam imaging and enzyme-linked immunoassay (ELISA). RESULTS: First, we report the safety and tolerability data as the primary outcome of this study. Adverse events (AE) suspected to be related to the study treatment (RTEAEs) are mostly grade 1-2. There are no grade 4 or 5 adverse events. VT1021 is safe and well tolerated in patients with solid tumors in this study. We report clinical responses as a secondary efficacy outcome. VT1021 demonstrates promising single-agent clinical activity in recurrent GBM (rGBM) in this study. Among 22 patients with rGBM, the overall disease control rate (DCR) is 45% (95% confidence interval, 0.24-0.67). Finally, we report the exploratory outcomes of this study. We show the clinical confirmation of TSP-1 induction and TME remodeling by VT1021. Our biomarker analysis identifies several plasmatic cytokines as potential biomarkers for future clinical studies. CONCLUSIONS: VT1021 is safe and well-tolerated in patients with solid tumors in a phase I expansion study. VT1021 has advanced to a phase II/III clinical study in glioblastoma (NCT03970447).
The network of cells that surround a tumor, the tumor microenvironment, can help cancers to grow. Therapies targeting the tumor microenvironment may help to stop tumor growth. One such therapy is VT1021. In animal models, VT1021 treatment stops tumor cells from growing by changing the tumor microenvironment. Here, we have tested VT1021 in a clinical trial and found that VT1021 treatment is safe and well tolerated in patients with cancer. We also see signs of efficacy in some patients and observe evidence that VT1021 modifies the tumor microenvironment, which may help to block tumor growth. Finally, we identified several markers from the blood that may help to predict which patients will best benefit from VT1021 treatment. With further testing in clinical trials, VT1021 may be a useful therapy for patients with cancer.
BACKGROUND AND PURPOSE: The canonical Kir6.2/SUR2A ventricular KATP channel is highly ATP-sensitive and remains closed under normal physiological conditions. These channels activate only when prolonged metabolic compromise causes significant ATP depletion and then shortens the action potential to reduce contractile activity. Pharmacological activation of KATP channels is cardioprotective, but physiologically, it is difficult to understand how these channels protect the heart if they only open under extreme metabolic stress. The presence of a second KATP channel population could help explain this. Here, we characterise the biophysical and pharmacological behaviours of a constitutively active Kir6.1-containing KATP channel in ventricular cardiomyocytes. EXPERIMENTAL APPROACH: Patch-clamp recordings from rat ventricular myocytes in combination with well-defined pharmacological modulators was used to characterise these newly identified K+ channels. Action potential recording, calcium (Fluo-4) fluorescence measurements and video edge detection of contractile function were used to assess functional consequences of channel modulation. KEY RESULTS: Our data show a ventricular K+ conductance whose biophysical characteristics and response to pharmacological modulation were consistent with Kir6.1-containing channels. These Kir6.1-containing channels lack the ATP-sensitivity of the canonical channels and are constitutively active. CONCLUSION AND IMPLICATIONS: We conclude there are two functionally distinct populations of ventricular KATP channels: constitutively active Kir6.1-containing channels that play an important role in fine-tuning the action potential and Kir6.2/SUR2A channels that activate with prolonged ischaemia to impart late-stage protection against catastrophic ATP depletion. Further research is required to determine whether Kir6.1 is an overlooked target in Comprehensive in vitro Proarrhythmia Assay (CiPA) cardiac safety screens.
Maize (Zea mays L.) is an important cereal and is affected by climate change. Therefore, the production of climate-smart maize is urgently needed by preserving diverse genetic backgrounds through the exploration of their genetic diversity. To achieve this, 96 maize inbred lines were used to screen for phenotypic yield-associated traits and grain quality parameters. These traits were studied across two different environments (Anand and Godhra) and polymorphic simple sequence repeat (SSR) markers were employed to investigate the genetic diversity, population structure, and trait-linked association. Genotype-environment interaction (GEI) reveals that most of the phenotypic traits were governed by the genotype itself across the environments, except for plant and ear height, which largely interact with the environment. The genotypic correlation was found to be positive and significant among protein, lysine and tryptophan content. Similarly, yield-attributing traits like ear girth, kernel rows ear-1, kernels row-1 and number of kernels ear-1 were strongly correlated to each other. Pair-wise genetic distance ranged from 0.0983 (1820194/T1 and 1820192/4-20) to 0.7377 (IGI-1101 and 1820168/T1). The SSRs can discriminate the maize population into three distinct groups and shortlisted two genotypes (IGI-1101 and 1820168/T1) as highly diverse lines. Out of the studied 136 SSRs, 61 were polymorphic to amplify a total of 131 alleles (2-3 per loci) with 0.46 average gene diversity. The Polymorphism Information Content (PIC) ranged from 0.24 (umc1578) to 0.58 (umc2252). Similarly, population structure analysis revealed three distinct groups with 19.79% admixture among the genotypes. Genome-wide scanning through a mixed linear model identifies the stable association of the markers umc2038, umc2050 and umc2296 with protein, umc2296 and umc2252 with tryptophan, and umc1535 and umc1303 with total soluble sugar. The obtained maize lines and SSRs can be utilized in future maize breeding programs in relation to other trait characterizations, developments, and subsequent molecular breeding performances for trait introgression into elite genotypes.
Objective: Determine the impact of limited implementation of a rapid blood culture identification (BCID) panel. Design: Retrospective cohort study. Methods: From February to April 2022, positive blood cultures identified via e-Plex BCID (Roche, Carlsbad, CA) were compared to those identified using standard microbial identification techniques. The primary outcomes assessed were time to optimal therapy, time to de-escalation of anti-MRSA (methicillin-resistant Staphylococcus aureus) agents, and time to de-escalation of anti-pseudomonal agents. Additional analysis investigated the impact of the availability of antimicrobial stewardship program support. This study was conducted at Grady Health System, a large metropolitan safety-net hospital in the southeastern United States. Results: A total of 253 blood cultures were included in this study (153 BCID and 100 standard). Blood culture identification use was associated with a reduction in median time to optimal antimicrobial therapy (43.4 vs 72.1 h, P < .001) and median time to de-escalation of anti-MRSA agents (27.7 vs 46.7 h, P = .006), and a trend towards reduction of median time to de-escalation of anti-pseudomonal agents (38.8 vs 54.8 h, P = .07). These reductions persisted when controlling for patient age, sex, intensive care unit status, Charlson Comorbidity Index, and antimicrobial stewardship program availability. Conclusions: Despite restricted use and lack of 24/7 antimicrobial stewardship program availability, BCID panel utilization was associated with earlier initiation of optimal therapy and pathogen identification with subsequent de-escalation of broad-spectrum antimicrobials, as compared to standard antimicrobial techniques. This suggests the potential for benefit from adopting novel diagnostic technologies outside of idealized fully-resourced settings.
This paper presents the novel use of a temporary percutaneous ventricular assist device (pVAD) in a 51-year-old man with an implanted durable left ventricular assist device (d-LVAD). The pre-existing left ventricular assist device was unable to successfully unload the left ventricle, and the addition of the temporary pVAD achieved successful unloading as well as a decrease in pulmonary artery pressures without compromising the function of the right ventricle allowing safe UNOS listing for orthotopic heart transplantation.
Heart Failure , Heart-Assist Devices , Prosthesis Design , Recovery of Function , Ventricular Function, Left , Humans , Male , Middle Aged , Treatment Outcome , Heart Failure/physiopathology , Heart Failure/therapy , Ventricular Function, Right , Arterial Pressure , Pulmonary Artery/physiopathology , Pulmonary Artery/diagnostic imaging , Prosthesis Implantation/instrumentation
Seaweeds have proven to be nutrient-dense and are rich in antioxidants, like phenolics, flavonoids, and other essential metabolites that help to provide their medicinal benefits. Non-targeted metabolite profiling of the tropical green seaweed Acrosiphonia orientalis showed the presence of numerous groups of contents, including sugars, essential amino acids, and fatty acids. Targeted metabolite profiling using HPLC identified 17 amino acids. The extract exhibited a very low half-maximal effective concentration (EC50) dosage for HeLa and Huh-7 cell lines, indicating a high likelihood of anticancer properties. A significant positive correlation was found between biological activities, such as antioxidation, scavenging, and reducing power with the phenolic and flavonoid contents. The extract revealed augmentation of proliferation in selected cervical cells, as it upregulated p53 1.3-fold, and downregulated important cancerous genes such as Cas-3 and DNMT 12- and 8-fold, respectively. An approximate 55-fold downregulation was observed in selected hepatic cell lines. Microarray analysis of hepatic cells indicated 0.27% and 0.07% upregulation of coding and non-coding genes, respectively, and 0.41% and 0.13% downregulation of coding and non-coding genes, respectively. As a consequence, it can be said that A. orientalis has possible medicinal use, such as anticancer activity, and therefore may be an intriguing food component that has potential as a regular dietary supplement.
Dietary Supplements , Seaweed , Humans , Seaweed/chemistry , Antioxidants/pharmacology , Plant Extracts/pharmacology , HeLa Cells , Metabolomics/methods , Cell Proliferation/drug effects , Cell Line, Tumor , Flavonoids/pharmacology , Flavonoids/analysis
Physical therapy (PT) benefits for critically ill patients are well recognized; however, little data exist on PT in patients receiving temporary mechanical circulatory support. In this single-center retrospective study (February 2017-January 2022), we analyzed 37 patients who received an axillary Impella device (Abiomed, Danvers, MA) and PT to "prehabilitate" them before durable left ventricular assist device (dLVAD) implantation. The Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility tool assessed the functional status at different points during admission. Immediately after Impella placement, the median AM-PAC score was 12.7 (interquartile range [IQR], 9-15), and the scores continued to significantly increase to 18.4 (IQR, 16-23) before dLVAD and up to 20.7 (IQR, 19-24) at discharge, indicating improved independence. No PT-related complications were reported. Thus, we hypothesize that critically ill patients initially deemed equivocal candidates may safely participate in PT while maximizing functional activities before dLVAD placement.
BACKGROUND: Ezabenlimab (BI 754091) is a humanised monoclonal antibody targeting programmed cell death protein-1. We report results from open-label, dose-escalation/expansion, Phase I trials that evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics and antitumour activity of ezabenlimab at the recommended Phase II dose in patients with selected advanced solid tumours. STUDY DESIGN: Study 1381.1 (NCT02952248) was conducted in Canada, the United Kingdom and the United States. Study 1381.4 (NCT03433898) was conducted in Japan. Study 1381.3 (NCT03780725) was conducted in the Netherlands. The primary endpoints were: number of patients experiencing dose-limiting toxicities (DLTs) in the first cycle (dose escalation parts), number of patients with DLTs during the entire treatment period and objective response (dose expansion part of Study 1381.1). RESULTS: Overall, 117 patients received ezabenlimab intravenously every 3 weeks (80 mg, n = 3; 240 mg, n = 111; 400 mg, n = 3). No DLTs were observed and the MTD was not reached. Fifty-eight patients (52.3%) had grade ≥ 3 adverse events, most commonly anaemia (10.8%) and fatigue (2.7%). In 111 assessed patients treated with ezabenlimab 240 mg, disease control rate was 56.8% and objective response rate was 16.2%. Three patients had complete response; at data cut-off (November 2021) one remained in response and was still receiving ongoing treatment (duration of response [DoR]: 906 days). Partial responses occurred across several tumour types; DoR ranged from 67 to 757 days. CONCLUSIONS: Ezabenlimab was well tolerated and associated with durable antitumour activity in multiple solid tumours, comparable to other immune checkpoint inhibitors in similar patient populations and treatment settings.
Immune Checkpoint Inhibitors , Neoplasms , Humans , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Canada , Immune Checkpoint Inhibitors/therapeutic use , Neoplasms/drug therapy , Neoplasms/pathology
INTRODUCTION: Androgen deprivation therapy (ADT) is commonly used to treat men with locally advanced or metastatic prostate cancer. Men receiving ADT experience numerous side effects and frequently report unmet supportive care needs. An essential part of quality cancer care is survivorship care. To date, an optimal effective approach to survivorship care for men with prostate cancer on ADT has not been described. This protocol describes a randomised trial of tele-based nurse-led survivorship that addresses this knowledge gap: (1) determine the effectiveness of a nurse-led survivorship care intervention (PCEssentials), relative to usual care, for improving health-related quality of life (HR-QoL) in men with prostate cancer undergoing ADT and (2) evaluate PCEssentials implementation strategies and outcomes, including cost-effectiveness, compared with usual care. METHODS AND ANALYSIS: This is an effectiveness-implementation hybrid (type 1) trial with participants randomised to one of two arms: (1) minimally enhanced usual care and (2) nurse-led prostate cancer survivorship essentials (PCEssentials) delivered over four tele-based sessions, with a booster session 5 months after session 1. Eligible participants are Australian men with prostate cancer commencing ADT and expected to be on ADT for a minimum of 12 months. Participants are followed up at 3, 6 and 12 months postrecruitment. Primary outcomes are HR-QoL and self-efficacy. Secondary outcomes are psychological distress, insomnia, fatigue and physical activity. A concurrent process evaluation with participants and study stakeholders will be undertaken to determine effectiveness of delivery of PCEssentials. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Metro South Health HREC (HREC/2021/QMS/79429). All participants are required to provide written informed consent. Outcomes of this trial will be published in peer-reviewed journals. The findings will be presented at conferences and meetings, local hospital departments, participating organisations/clinical services, and university seminars, and communicated at community and consumer-led forums. TRIAL REGISTRATION NUMBER: ACTRN12622000025730.
Cancer Survivors , Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/psychology , Quality of Life/psychology , Androgen Antagonists/therapeutic use , Androgens , Prostate , Survivorship , Nurse's Role , Australia , Randomized Controlled Trials as Topic
As focus for exploration of Mars transitions from current robotic explorers to development of crewed missions, it remains important to protect the integrity of scientific investigations at Mars, as well as protect the Earth's biosphere from any potential harmful effects from returned martian material. This is the discipline of planetary protection, and the Committee on Space Research (COSPAR) maintains the consensus international policy and guidelines on how this is implemented. Based on National Aeronautics and Space Administration (NASA) and European Space Agency (ESA) studies that began in 2001, COSPAR adopted principles and guidelines for human missions to Mars in 2008. At that point, it was clear that to move from those qualitative provisions, a great deal of work and interaction with spacecraft designers would be necessary to generate meaningful quantitative recommendations that could embody the intent of the Outer Space Treaty (Article IX) in the design of such missions. Beginning in 2016, COSPAR then sponsored a multiyear interdisciplinary meeting series to address planetary protection "knowledge gaps" (KGs) with the intent of adapting and extending the current robotic mission-focused Planetary Protection Policy to support the design and implementation of crewed and hybrid exploration missions. This article describes the outcome of the interdisciplinary COSPAR meeting series, to describe and address these KGs, as well as identify potential paths to gap closure. It includes the background scientific basis for each topic area and knowledge updates since the meeting series ended. In particular, credible solutions for KG closure are described for the three topic areas of (1) microbial monitoring of spacecraft and crew health; (2) natural transport (and survival) of terrestrial microbial contamination at Mars, and (3) the technology and operation of spacecraft systems for contamination control. The article includes a KG data table on these topic areas, which is intended to be a point of departure for making future progress in developing an end-to-end planetary protection requirements implementation solution for a crewed mission to Mars. Overall, the workshop series has provided evidence of the feasibility of planetary protection implementation for a crewed Mars mission, given (1) the establishment of needed zoning, emission, transport, and survival parameters for terrestrial biological contamination and (2) the creation of an accepted risk-based compliance approach for adoption by spacefaring actors including national space agencies and commercial/nongovernment organizations.
Mars , Space Flight , Humans , Extraterrestrial Environment , Exobiology , Containment of Biohazards , Spacecraft
Enhancing carbohydrate export from source to sink tissues is considered to be a realistic approach for improving photosynthetic efficiency and crop yield. The rice sucrose transporters OsSUT1, OsSWEET11a and OsSWEET14 contribute to sucrose phloem loading and seed filling. Crucially, Xanthomonas oryzae pv. oryzae (Xoo) infection in rice enhances the expression of OsSWEET11a and OsSWEET14 genes, and causes leaf blight. Here we show that co-overexpression of OsSUT1, OsSWEET11a and OsSWEET14 in rice reduced sucrose synthesis and transport leading to lower growth and yield but reduced susceptibility to Xoo relative to controls. The immunity-related hypersensitive response (HR) was enhanced in the transformed lines as indicated by the increased expression of defence genes, higher salicylic acid content and presence of HR lesions on the leaves. The results suggest that the increased expression of OsSWEET11a and OsSWEET14 in rice is perceived as a pathogen (Xoo) attack that triggers HR and results in constitutive activation of plant defences that are related to the signalling pathways of pathogen starvation. These findings provide a mechanistic basis for the trade-off between plant growth and immunity because decreased susceptibility against Xoo compromised plant growth and yield.
Gene Expression Regulation, Plant , Membrane Transport Proteins , Oryza , Plant Diseases , Plant Immunity , Plant Proteins , Plants, Genetically Modified , Salicylic Acid , Sucrose , Xanthomonas , Oryza/microbiology , Oryza/genetics , Oryza/immunology , Oryza/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Xanthomonas/physiology , Plant Diseases/microbiology , Plant Diseases/immunology , Sucrose/metabolism , Membrane Transport Proteins/metabolism , Membrane Transport Proteins/genetics , Salicylic Acid/metabolism , Plant Leaves/metabolism , Plant Leaves/immunology
BACKGROUND: Decisions regarding resuscitation after cardiac arrest are critical from ethical, patient satisfaction, outcome, and healthcare cost standpoints. Physician-reported discussion barriers include topic discomfort, fear of time commitment, and difficulty articulating end-of-life concepts. The influence of language used in these discussions has not been tested. This study explored whether utilizing the alternate term "allow (a) natural death" changed code status decisions in hospitalized patients versus "do not resuscitate" (DNR). METHODS: All patients age 65 and over admitted to a general medicine hospital teaching service were screened (English-speaking, not ICU-level care, no active psychiatric illness, no substance misuse, no active DNR). Participants were randomized to resuscitation discussions with either DNR or "allow natural death" as the "no code" phrasing. Outcomes included patient resuscitation decision, satisfaction with and duration of the conversation, and decision correlation with illness severity and predicted resuscitation success. RESULTS: 102 participants were randomized to the "allow natural death" (N = 49) or DNR (N = 53) arms. The overall "no code" rate for our sample of hospitalized general medicine inpatients age >65 was 16.7%, with 13% in the DNR and 20.4% in the "allow natural death" arms (p = 0.35). Discussion length was similar in the DNR and "allow natural death" arms (3.9 + 3.2 vs. 4.9 + 3.9 minutes), and not significantly different (p = 0.53). Over 90% of participants were highly satisfied with their code status decision, without difference between arms (p = 0.49). CONCLUSIONS: Participants' code status discussions did not differ in "no code" rate between "allow natural death" and DNR arms but were short in length and had high patient satisfaction. Previously reported code status discussion barriers were not encountered. It is appropriate to screen code status in all hospitalized patients regardless of phrasing used.
OBJECTIVE: This systematic review (PROSPERO ID: CRD42022226375) aimed to identify the eHealth literacy of men with prostate cancer, and their caregivers. METHODS: 8 databases (MEDLINE, SCOPUS, EMBASE, Web Of Science, PsycINFO, ERIC, CINAHL, Cochrane CENTRAL) and grey literature sources (e.g. Google Scholar) were searched from inception to December 2023. Articles were included if assessing eHealth/digital literacy of men with prostate cancer, or their carers', and health outcome associations. Formats such as case reports, and review papers were excluded. Records and full texts underwent independent screening and data extraction. Author disagreements were resolved by discussion. The Mixed Methods Appraisal Tool (MMAT) was used to appraise included literature, with narrative synthesis of results. RESULTS: 21,581 records were retrieved, with 7 articles satisfying inclusion criteria. A heterogenous field was characterised with lack of modern eHealth literacy measurement tools identified. Results suggest novice eHealth literacy using web 1.0 technologies. Non-validated measures of literacy demonstrate mixed results, while health outcome effects limited in scope and reliability. CONCLUSION: Prostate cancer survivors' eHealth literacy levels is likely novice, and requires further investigation. PRACTICE IMPLICATIONS: Digital technologies/resources implemented as part of patient communication practices should be vetted for quality, and tailored to patients' eHealth literacy abilities and/or needs.
Health Literacy , Prostatic Neoplasms , Telemedicine , Male , Humans , Reproducibility of Results , Telemedicine/methods , Prostatic Neoplasms/therapy , Caregivers
