Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Impact of Psychopathy and Narcissism on Employees’ Adverse Outcomes: A Perspective of Ethical Climate Theory and Threatened-Egotism Model

This study examines the impact of psychopathic and narcissist personalities on employees' adverse outcomes. Additionally, this study investigates the intervening mechanism of workplace incivility among the relationship between psychopathic and narcissist personalities and adverse outcomes. Furthermore, the interactive impact of Islamic work values was also tested between the association of workplace incivility and adverse outcomes. Using the purposive sampling technique, data was collected through a survey method from 404 permanent employees of a public sector organization in two different time lags. PROCESS-macro was used to test indirect, interactive, and moderated mediation effects.  The findings of this study confirm the direct effect relationship between that psychopathic and narcissist personalities and employees’ adverse outcomes. Further, this study confirms that workplace incivility indirectly enhances the adverse outcomes of employees. Finally, the study findings revealed that a higher level of Islamic work values reduces the adverse outcomes of the employees having psychopathic and narcissistic personality characteristics. We also tested moderated mediation model, which disclosed that a higher level of Islamic work values reduces the negativity level of psychopathic personalities that further decreases the level of counterproductive work behaviors via workplace incivility. However, there was no moderating role of Islamic work values to reduce narcissist personalities' negativity levels and reduce counterproductive work behaviors via workplace incivility. The present study by providing information to the management of the public sector organizations on how they can overcome the negative behaviors and outcomes of their workforce through the implementation of the Islamic ethical system. This attempt contributed to ethical climate theory and threatened the egotism model by explaining that negative personality traits predict uncivil behaviors, which further lead to adverse outcomes. This study further contributes that the ethical climate of the organization helps the individuals to overcome the negativity of their personality and negative behaviors as well

Comparative Study on the Physio-Biochemical Responses of Spring and Winter Barley Genotypes under Vernalized and Greenhouse Conditions

In barley (Hordeum vulgare L.) breeding, heading date is one of the most important agricultural traits that is essential for the completion of its life cycle. Certain endogenous and environmental factors regulate floral transition, morphing the complex genetic mechanism of the heading phase, which could serve as a premise of orchestration for improved yields. To elaborate the network of genetic and environmental signals, a hydroponic experiment was carried out using two spring (i.e., DM65 and DM70) and two winter barley genotypes (i.e., DM269 and DM385). Our results confirmed that the vernalized environment produced a substantial reduction in plant height, biomass and photosynthetic activity compared with the control plants. A noticeable increase in oxidative stress was exhibited by DM65 and DM70 plants compared with their respective controls at 20 °C, while no significant difference was observed for any genotype grown in the greenhouse (25 °C). Simultaneously, increased antioxidant enzyme activity in winter barley genotypes showed a defensive mechanism under vernalized conditions (4 °C). Furthermore, the expression of key regulatory flowering genes revealed that the vernalization gene (HvVRN1) is the key regulator of floral induction after cold exposure, whereas Photoperiod Response Locus 1 (HvPpd-H1) had significantly higher expression under greenhouse conditions, along with Phytochrome C (HvPHY-C), validating their involvement as upstream heading time regulators. These findings contribute to enriching the study of environmental signals that substantially modulate the complex mechanism of barley heading date

Comparative Study on the Physio-Biochemical Responses of Spring and Winter Barley Genotypes under Vernalized and Greenhouse Conditions

In barley (Hordeum vulgare L.) breeding, heading date is one of the most important agricultural traits that is essential for the completion of its life cycle. Certain endogenous and environmental factors regulate floral transition, morphing the complex genetic mechanism of the heading phase, which could serve as a premise of orchestration for improved yields. To elaborate the network of genetic and environmental signals, a hydroponic experiment was carried out using two spring (i.e., DM65 and DM70) and two winter barley genotypes (i.e., DM269 and DM385). Our results confirmed that the vernalized environment produced a substantial reduction in plant height, biomass and photosynthetic activity compared with the control plants. A noticeable increase in oxidative stress was exhibited by DM65 and DM70 plants compared with their respective controls at 20 °C, while no significant difference was observed for any genotype grown in the greenhouse (25 °C). Simultaneously, increased antioxidant enzyme activity in winter barley genotypes showed a defensive mechanism under vernalized conditions (4 °C). Furthermore, the expression of key regulatory flowering genes revealed that the vernalization gene (HvVRN1) is the key regulator of floral induction after cold exposure, whereas Photoperiod Response Locus 1 (HvPpd-H1) had significantly higher expression under greenhouse conditions, along with Phytochrome C (HvPHY-C), validating their involvement as upstream heading time regulators. These findings contribute to enriching the study of environmental signals that substantially modulate the complex mechanism of barley heading date

Physio-ultrastructural footprints and iTRAQ-based proteomic approach unravel the role of Piriformospora indica-colonization in counteracting cadmium toxicity in rice

Due to its immense capability to concentrate in rice grain and ultimately in food chain, cadmium (Cd) has become the cause of an elevated concern among agriculturists, scientists and the environmental activists. Symbiotic association of Piriformospora indica (P. indica) has been characterized as a potential aid in combating heavy metal stress in plants for sustainable crop production but our scant knowledge regarding ameliorative tendency of P. indica against Cd, specifically in rice, necessitates an in-depth investigation. This study aimed at elaborating the underlying mechanisms involved in P. indica-mediated tolerance against Cd stress in two rice genotypes, IR8 and ZX1H, varying in Cd accumulation pattern. Either colonized or un-inoculated with P. indica, seedlings of both genotypes were subjected to Cd stress. The results showed that P. indica colonization significantly supported plant biomass, photosynthetic attributes and chlorophyll contents in Cd stressed plants. P. indica colonization sustained chloroplast integrity and reduced Cd translocation (46% and 64%), significantly lowering malondialdehyde (MDA) content (11.3% and 50.4%) compared to uninoculated roots under Cd stress in IR8 and ZX1H, respectively. A genotypic difference was evident when a 2-fold enhancement in root peroxidase (POD) activity was recorded in P. indica colonized IR8 plants as compared to ZX1H. The root proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ) and the results showed that P. indica alleviates Cd stress in rice via down-regulation of key glycolysis cycle enzymes in a bid to reduce energy consumption by the plants and possibly re-directing it to Cd defense response pathways; and up-regulation of glutamine synthetase, a key enzyme in the L-Arg-dependent pathway for nitric oxide (NO) production, which acts as a stress signaling molecule, thus conferring tolerance by reduction of NO-mediated modification of essential proteins in response to Cd stress. Conclusively, both the tested genotypes benefited from P. indica symbiosis at varying levels by an enhanced detoxification capacity and signaling efficiency in response to stress. Hence, a step forward towards the employment of an environmentally sound and self-renewing approach holding the hope for a healthy future

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

BackgroundTranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.MethodsWe did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.FindingsBetween July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98).InterpretationWe found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial.</div