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Risk stratification of patients with acute pulmonary embolism (PE) assists with the selection of appropriate initial therapy and treatment setting. Patients with acute symptomatic PE that present with arterial hypotension or shock have a high risk of death, and treatment guidelines recommend strong consideration of reperfusion in this setting. For haemodynamically stable patients with PE, the combination of a negative clinical prognostic score and the absence of computed tomography-assessed right ventricle enlargement may accurately identify those at low-risk of short-term complications after the diagnosis of PE, and such patients might benefit from an abbreviated hospital stay or outpatient therapy. Some evidence suggests that the accumulation of factors indicating worse outcomes from PE on standard anticoagulation identifies the more severe stable patients with acute PE who might benefit from intensive monitoring and recanalization procedures, particularly if haemodynamic deterioration occurs. Current risk classifications have several shortcomings that might adversely affect clinical and healthcare decisions. Ongoing initiatives aim to address many of those shortcomings, and will hopefully help optimize risk stratification algorithms and treatment strategies.

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Venous thromboembolism (VTE) is a common, serious condition that requires anticoagulation for at least three months to prevent recurrence and long-term complications. After this initial period, the decision to continue or stop anticoagulation depends on the balance between the risk of recurrent VTE and the risk of bleeding. Established guidelines suggest short-term anticoagulation for VTE caused by transient factors and indefinite anticoagulation for recurrent or cancer-associated VTE. However, for a first unprovoked VTE, decision-making remains challenging. Current predictive scores for recurrence and bleeding are not sufficiently reliable, and the safety and efficacy of reduced-dose anticoagulation remain unclear. In the future, precision and patient-centred medicine may improve treatment decisions in this area.

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This study generated evidence to guide anticoagulation in patients with VTE after vaccination for COVID-19. We provided data on the low recurrence rate after cessation of anticoagulant therapy and the findings for this study offer timely insights into the management of a potentially vaccine-related adverse event.

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OBJECTIVE: To estimate the prevalence of inappropriate use of prophylaxis to prevent venous thromboembolism (VTE) in patients with medical diseases admitted to hospital from the emergency department. To explore variables associated with inappropriate thromboprophylaxis. METHODS: Prospective multicenter cohort study in 15 hospital emergency departments. We included patients admitted for a medical condition during 7 days in the first quarter of 2022. We assessed risk for VTE with the Padua Prediction Score (PPS). Inappropriate thromboprophylaxis was defined by failure to prescribe prophylaxis in patients with a high-risk PPS assessment unless there were absolute contraindications (active bleeding or severe thrombopenia) or, alternatively, the prescription of prophylaxis in patients with a low-risk PPS assessment or absolute contraindications. A logistic regression model was adjusted for risk level to identify variables associated with inappropriate use of thromboprophylaxis. RESULTS: Of a total of 630 patients included, 450 (71.4%) had PPS scores indicating high risk for VTE; 180 patients were at low risk. Thromboprophylaxis was inappropriate in 248 patients (39.4%): 165 high-risk patients who received no prophylaxis, 82 low-risk patients who were nonetheless treated, and 1 patient who was treated in spite of severe thrombopenia. Odds ratios (ORs) revealed that the variables associated with inappropriate use of thromboprophylaxis were trauma or recent surgery (OR, 5.53; 95% CI, 1.58-19.34), presence of factors indicating risk for bleeding (OR, 2.61; 95% CI, 1.44-4.73), and hospital admission for either urinary tract infection (OR, 2.29; 95% CI, 1.07-4.87) or gastrointestinal disease (OR, 4.30; 95% CI, 1.71-10.85). CONCLUSIONS: The inappropriate use of thromboprophylaxis in Spanish emergency departments is high and associated with certain clinical characteristics.

OBJETIVO: Evaluar la inadecuación de la tromboprofilaxis farmacológica, según la escala Padua (PPS), para prevenir la enfermedad tromboembólica venosa (ETV) entre los pacientes que ingresan desde el servicio de urgencias hospitalario (SUH) por patología médica, así como las variables asociadas a su uso inadecuado. METODO: Estudio de cohortes, prospectivo, multicéntrico donde participaron 15 SUH. Se incluyeron los pacientes atendidos que requirieron ingreso por enfermedad médica durante 7 días del primer trimestre de 2022. La inadecuación de la tromboprofilaxis farmacológica se definió como la no utilización en pacientes clasificados por PPS de alto riesgo sin contraindicaciones absolutas para su uso (hemorragia activa o trombopenia grave) o su utilización en pacientes de riesgo bajo o con contraindicaciones absolutas. Se ajustó, para cada grupo de riesgo, un modelo de regresión logística para identificar las variables asociadas a la inadecuación. RESULTADOS: Se incluyeron 630 pacientes, 450 (71,4%) tenían riesgo alto y 180 (28,6%) riesgo bajo para ETV según la PPS. De ellos, la tromboprofilaxis fue inadecuada en 248 pacientes (39,4%) (165 tenían riesgo alto pero no recibieron tromboprofilaxis, 1 la recibió teniendo trombopenia grave y 82 tenían riesgo bajo pero recibieron tromboprofilaxis). Las variables asociadas con la inadecuación en pacientes de alto riesgo fueron trauma o cirugía recientes con odds ratio (OR) de OR 5,53 (IC 95%: 1,58-19,34), presencia de factores de riesgo hemorrágico con OR de 2,61 (IC 95%: 1,44-4,73), e infección del tracto urinario con OR de 2,29 (IC 95%: 1,07-4,87) y enfermedad gastrointestinal con OR de 4,30 (IC 95%: 1,71-10,85) como motivos de ingreso. CONCLUSIONES: En los SUH españoles, el uso inadecuado de la tromboprofilaxis farmacológica es elevado. Algunas características clínicas se asocian al uso inadecuado de dicha tromboprofilaxis.

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Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading to neurodegenerative disease. Factors that regulate the extrusion of large vesicles, such as exophers produced by proteostressed C. elegans touch neurons, are poorly understood. Here, we document that mechanical force can significantly potentiate exopher extrusion from proteostressed neurons. Exopher production from the C. elegans ALMR neuron peaks at adult day 2 or 3, coinciding with the C. elegans reproductive peak. Genetic disruption of C. elegans germline, sperm, oocytes, or egg/early embryo production can strongly suppress exopher extrusion from the ALMR neurons during the peak period. Conversely, restoring egg production at the late reproductive phase through mating with males or inducing egg retention via genetic interventions that block egg-laying can strongly increase ALMR exopher production. Overall, genetic interventions that promote ALMR exopher production are associated with expanded uterus lengths and genetic interventions that suppress ALMR exopher production are associated with shorter uterus lengths. In addition to the impact of fertilized eggs, ALMR exopher production can be enhanced by filling the uterus with oocytes, dead eggs, or even fluid, supporting that distention consequences, rather than the presence of fertilized eggs, constitute the exopher-inducing stimulus. We conclude that the mechanical force of uterine occupation potentiates exopher extrusion from proximal proteostressed maternal neurons. Our observations draw attention to the potential importance of mechanical signaling in extracellular vesicle production and in aggregate spreading mechanisms, making a case for enhanced attention to mechanobiology in neurodegenerative disease.

Neurons are specialized cells in the brain and nervous system that transmit signals between the brain and the rest of the body, enabling humans and animals to react to internal and external stimuli. For this communication system to function effectively, neurons must remain healthy. Neurons maintain their function in a variety of ways, including by removing excess or damaged cellular components (such as organelles and protein aggregates) that could compromise neuron function. One way to do this is by extruding organelles and aggregates. During 'extrusion events', the material to be removed is gathered within a budding portion of the plasma membrane, which forms a vesicle that ejects the material from the neuron. However, the factors driving the extrusion process remained unknown. To investigate, Wang, Guasp, Salam et al. conducted experiments in the roundworm Caenorhabditis elegans, finding that the number of extrusion events in a certain type of neuron increases at the peak of reproduction. More specifically, a greater number of extrusion events were associated with the presence of fertilized eggs, which accumulate in the uterus before they are laid. Disrupting eggs, sperm or the fertilization process suppressed the increase in extrusion events, suggesting the presence of fertilized eggs is responsible. To determine how the eggs might trigger extrusion events, Wang et al. stretched the uterus using dead eggs, unfertilized eggs or by injecting fluid, finding that each of these approaches increased the number of extrusion events. Further analysis suggests that this mechanical stretching of the uterus signals to the neurons that reproduction has started, encouraging the neurons to remove old components and optimize their function. Wang et al. hypothesize that this stretch response could support neuronal behaviors that aid in successful reproduction, such as sensing food and selecting where to lay eggs. The findings increase our understanding of the factors that trigger vesicle extrusion in living organisms. These observations could have implications for human neurodegenerative diseases such as Alzheimer's disease, in which protein aggregates accumulate in neurons. It is possible that mechanical signals generated by factors associated with Alzheimer's disease, such as high blood pressure, could influence neuronal extrusion and contribute to some of the mechanisms underlying aggregate transfer in neurodegenerative diseases.

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BACKGROUND: Pulmonary embolism (PE) and acute exacerbation of chronic obstructive pulmonary disease (COPD) have similar clinical symptoms, making PE diagnosis challenging. Previous studies have shown that the prevalence of PE among COPD patients admitted with worsening respiratory symptoms was not negligible, but that systematic search for PE did not provide a clinical benefit. Predictive factors for PE remain unknown. OBJECTIVE: to identify predictive factors for PE among COPD patients with worsening respiratory symptoms. METHODS: We conducted an individual participant data meta-analysis which included the patients from the prospective PEP cohort and those randomized to the intervention arm in the SLICE trial which included a systematic search for PE in COPD patients admitted for worsening respiratory symptoms. Univariable and multivariable analysis were used to assess factors associated with the diagnosis of PE during the initial management. RESULTS: Among 1110 COPD patients, PE was diagnosed in 61 (5.49 %; 95 %CI 4.15 %-6.84 %). In univariable analysis, BNP (Brain natriuretic peptide) (odds ratio [OR] 1.02 per 100 ng/L increase, 95 %CI 1.01-1.04), prothrombin time (OR 0.78, 95 %CI 0.65-0.94), fibrinogen (OR 0.80, 95 %CI 0.64-0.98), atrial fibrillation (OR 4.74, 95 %CI 1.84-10.80), respiratory rate ≥30 min (OR 2.34, 95 %CI 1.13-4.6) and recent medical immobilization (OR 1.79, 95 %CI 0.99-3.13]) were associated with the risk of PE diagnosed during the initial management. In multivariable analysis, respiratory rate ≥30 (OR 2.77, 95 %CI 1.08-6.71) was a predictive factor for PE, as well as BNP (OR 1.02, 95 %CI 1.00-1.05) with an area under the curve =0.64, negative predictive value =0.15 (95 %CI 0.09-0.23), sensitivity =0.78 (95 %CI 0.74-0.82) and specificity =0.46 (95 %CI 0.29-0.63). CONCLUSION: Among patients with COPD admitted for worsening respiratory symptoms, respiratory rate and BNP levels are predictor of PE, but with limited discriminatory power.

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BACKGROUND AND OBJECTIVES: Craniosynostosis can lead to progressive cranial and skull base deformities and can be associated with increased intracranial pressure (ICP), ophthalmological manifestations, behavioral changes, and developmental delay. Most published data on the incidence of elevated ICP include older children undergoing open surgical correction. Endoscopic-assisted release of fused sutures with postoperative helmet therapy is an established method for managing craniosynostosis presenting at an early age; however, the immediate effect of this approach on ICP in a young cohort has not been previously reported. METHODS: Prospective data on 52 children undergoing endoscopic-assisted release of stenosed cranial sutures were included. Individuals were excluded if they underwent open correction or had previous cranial surgery. Individuals underwent a standardized endoscopic approach for each suture type. ICP was measured using an intraparenchymal sensor both before creation of the neosuture and after complete release of the stenosed suture. An ICP reading of >10 mm Hg was considered elevated. RESULTS: The mean age was 5.3 months, range 1 to 32 months, and 94% was younger than 12 months. The mean opening pressure was 12.7 mm Hg, and the mean closing pressure was 2.9 mm Hg. Opening ICP ≥10 mm Hg was present in 58%, ≥15 mm Hg was present in 31%, and ≥20 mm Hg was present in 23%. No patient had an ICP above 10 mm Hg at closing. The mean percentage change in ICP among all craniosynostosis cases was a 64% decrease. Optic disk swelling was identified in 28 children preoperatively and improved in 22 children at follow-up. CONCLUSION: Elevated ICP may occur in infants with craniosynostosis at higher rates than previously reported. Endoscopic-assisted craniectomy has an immediate effect on lowering ICP and improving postoperative ophthalmological findings.

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MicroRNAs (miRNAs) are small noncoding RNAs that are critical for the regulation of multiple physiological and pathological processes, thus holding great clinical potential. However, the therapeutic applications of miRNAs are severely limited by their biological instability and poor intracellular delivery. Herein, we describe a dual-layers surface engineering strategy to design an efficient miRNA delivery nanosystem based on metal-organic frameworks (MOFs) incorporating lipid coating. The resulting nanoparticle system was demonstrated to protect miRNA from ribonuclease degradation, enhance cellular uptake and facilitate lysosomal escape. These ensured effective miRNA mediated gene therapy, which synergized with MOF-specific photodynamic therapy and pre-encapsulated doxorubicin (Dox) chemotherapy to provide a multifunctional with therapeutic effectiveness against cencer cells The mechanisms of miRNA binding and Dox loading were revealed, demonstrating the potential of the present MOFs surface-engineered strategy to overcome their inherent pore-size restriction for macromolecular miRNA carrying, enableefficient co-delivery. In vitro studies revealed the potential of our multifunctional system for miRNA delivery and the demonstrated the therapeutic effectiveness against cancer cells, thereby providing a versatile all-in-one MOFs strategy for delivery of nucleic acids and diverse therapeutic molecules in synergistic therapy.

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BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis. METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model. RESULTS: The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]. CONCLUSIONS: The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.

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STUDY OBJECTIVES: The STOP-Bang questionnaire is a validated screening tool for obstructive sleep apnea (OSA). We conducted this study to validate it among patients hospitalized with acute symptomatic pulmonary embolism (PE). METHODS: This prospective cohort study enrolled consecutive stable patients with acute PE who underwent an overnight sleep study within 7 days after diagnosis. Our outcomes were: i) the STOP-Bang questionnaire's utility for risk stratification, ii) the discrimination of the STOP-Bang questionnaire categories, iii) the false negative rate of STOP-Bang questionnaire prediction, and iv) the clinical utility of the STOP-Bang questionnaire to exclude OSA. We also calculated the test performance characteristics to predict OSA. RESULTS: During the study period, 268 patients completed a sleep study. OSA was found in 47% of patients. OSA incidence in low-, moderate-, and high-risk STOP-Bang groups was 22.4%, 48.2%, and 61.5%, respectively (P <0.001). The area under the receiver operating characteristics curve of the STOP-Bang questionnaire for risk of OSA was 0.65. The false negative rate of a low-risk STOP-Bang questionnaire result to rule out OSA was 22.4% and the clinical utility was 21.6%. The sensitivity was 89.8% (97.2% for men and 80.4% for women). CONCLUSIONS: The STOP-Bang questionnaire showed poor discrimination for the risk of OSA in hospitalized patients with acute symptomatic PE. It had a high false negative rate and a low clinical utility. The STOP-Bang questionnaire had a good sensitivity in men, and might be used to rule out OSA in this population.

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Background: The clinical relevance of recurrent venous thromboembolism (VTE) after discontinuing anticoagulation in patients with COVID-19-associated VTE remains uncertain. We estimated the incidence rates and mortality of VTE recurrences developing after discontinuing anticoagulation in patients with COVID-19-associated VTE. Methods: A prospective, multicenter, non-interventional study was conducted between March 25, 2020, and July 26, 2023, including patients who had discontinued anticoagulation after at least 3 months of therapy. All patients from the registry were analyzed during the study period to verify inclusion criteria. Patients with superficial vein thrombosis, those who did not receive at least 3 months of anticoagulant therapy, and those who were followed for less than 15 days after discontinuing anticoagulation were excluded. Outcomes were: 1) Incidence rates of symptomatic VTE recurrences, and 2) fatal PE. The rate of VTE recurrences was defined as the number of patients with recurrent VTE divided by the patient-years at risk of recurrent VTE during the period when anticoagulation was discontinued. Findings: Among 1106 patients with COVID-19-associated VTE (age 62.3 ± 14.4 years; 62.9% male) followed-up for 12.5 months (p25-75, 6.3-20.1) after discontinuing anticoagulation, there were 38 VTE recurrences (3.5%, 95% confidence interval [CI]: 2.5-4.7%), with a rate of 3.1 per 100 patient-years (95% CI: 2.2-4.2). No patient died of recurrent PE (0%, 95% CI: 0-7.6%). Subgroup analyses showed that patients with diagnosis in 2021-2022 (vs. 2020) (Hazard ratio [HR] 2.86; 95% CI 1.45-5.68) or those with isolated deep vein thrombosis (vs. pulmonary embolism) (HR 2.31; 95% CI 1.19-4.49) had significantly higher rates of VTE recurrences. Interpretation: In patients with COVID-19-associated VTE who discontinued anticoagulation after at least 3 months of treatment, the incidence rate of recurrent VTE and the case-fatality rate was low. Therefore, it conceivable that long-term anticoagulation may not be required for many patients with COVID-19-associated VTE, although further research is needed to confirm these findings. Funding: Sanofi and Rovi, Sanofi Spain.

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Patellofemoral arthroplasty (PFA) has emerged as an alternative bone-preserving surgical option for treating isolated symptomatic patellofemoral osteoarthritis that better replicates the natural knee kinematics compared with total knee arthroplasty. Achieving successful outcomes in PFA relies on meticulous patient selection, proper surgical technique, and appropriate implant choice and placement. Recent advancements in inlay trochlea implants, allowing for customized and anatomic joint line reconstruction with less bone resection, have demonstrated significant improvements in functional outcome scores and pain relief. This Technical Note aims to provide insights into the surgical technique of PFA with inlay implants, highlighting key considerations and potential challenges. It also assists surgeons in making informed decisions regarding the choice between standard and dysplastic inlay implants, while suggesting concurrent procedures to optimize tracking and overall outcomes.

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BACKGROUND AND OBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism and a major cause of chronic pulmonary hypertension leading to right heart failure and death. While pulmonary endarterectomy is the treatment of choice, some patients might benefit from medical therapy or balloon pulmonary angioplasty. Sex differences in outcomes of these therapies are not well characterized. MATERIAL AND METHODS: We conducted a systematic review and meta-analysis to investigate sex differences in outcomes of various therapies for CTEPH. We searched MEDLINE, PubMed, Embase, CINAHL and the Cochrane Library databases between January 1, 2010 and April 30, 2021, published in English. We pooled incidence estimates using random-effects meta-analyses. We evaluated heterogeneity using the I2 statistic. We assessed publication bias using Begg's and Egger's tests. This study is registered in PROSPERO, CRD42021268504. RESULTS: A total of 19 studies met the eligibility criteria, but only 3 trials provided separate outcomes for women and men. Two studies evaluated the efficacy of BPA, and one study evaluated the efficacy of riociguat (129 patients). Overall, 57.3% of patients were women and 62.6% were in functional class III. Mean time of follow-up was 55.5 (SD 26.1) weeks. Women showed a significantly better response in cardiac index (mean difference [MD], 0.10L/min/m2; 95% confidence interval [CI], 0.04-0.16; I2=0%; P=0.001). Alternatively, the reduction of pulmonary vascular resistances was significantly higher for men than for women (MD, 161.17dynscm-5; 95% CI, 67.99-254.35; I2=0%; P=0.0007). CONCLUSIONS: Women and men might show different hemodynamic responses to riociguat or BPA for CTEPH.

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Objectives: The core objectives of this study centre on enhancing the quality of life and well-being of individuals diagnosed with Parkinson's and Alzheimer's diseases. Our aim is to facilitate the monitoring of patient information, benefiting both caregivers and healthcare professionals. Methods: As part of the PROCare4Life platform sensorial ecosystem, a web application with six engaging cognitive games focusing on developing cognitive training and stimulating brain activity are developed. A set of metrics calculated by the application feed machine learning predictive models to evaluate the cognitive status and evolution over time. Long-term analysis of the daily cognitive ability information is used to generate high-level outcomes and identify deviations for each patient from the multimodal fusion engine. And based on these results, a recommender system provides a set of personalized notifications. Results: A 3-month pilot study that took place in five different countries shows the results obtained from 93 patients. An average of 22.4 games were completed per day and the recommender system generated a total of 260 game notifications, 37.7% of them were marked as read by the patients. The Cognitive State Score and the Deviations in Cognitive Abilities measurement, calculated by the multimodal fusion engine, when used in conjunction present a good overview of the patient's current state and potential deviations. Conclusion: The cognitive games application was well-received by elderly individuals who took part in the study. This tool can be valuable for caregivers and healthcare providers in assessing the cognitive function of patients through engaging in cognitive games.

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This work presents a straightforward, room-temperature synthesis of a robust {[Fe(atrz)3](OTs)2}n monolith. This approach offers a green alternative to traditional nanoparticle synthesis for manipulating spin crossover (SCO) behaviour. The monolith exhibits a more gradual SCO transition at lower temperatures compared to the bulk material, aligning with observations in smaller particle systems. Notably, the synthesis employs a solvent- and surfactant-free approach, simplifying the process and potentially reducing environmental impact, aligning with the principles of green chemistry.

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Chloride (Cl-) is traditionally categorized as an antagonist of nitrate (NO3-) because Cl- hinders plant NO3- transport and accumulation. However, we have recently defined Cl- as a beneficial macronutrient for higher plants, due to specific functions that lead to more efficient use of water, nitrogen (N) and CO2 under optimal N and water supply. When accumulated in leaves at macronutrient levels, Cl- promotes growth through osmotic, physiological, metabolic, anatomical and cellular changes that improve plant performance under optimal NO3- nutrition. Nitrate over-fertilization in agriculture can adversely affect crop yield and nature, while its deficiency limits plant growth. To study the relationship between Cl- nutrition and NO3- availability, we have characterized different physiological responses such as growth and yield, N-use efficiency, water status, photosynthesis, leaf anatomy, pigments and antioxidants in tomato plants treated with or without 5 mM Cl- salts and increasing NO3- treatments (3-15 mM). First, we have demonstrated that 5 mM Cl- application can reduce the use of NO3- in the nutrient solution by up to half without detriment to plant growth and yield in tomato and other horticultural plants. Second, Cl- application reduced stress symptoms and improved plant growth under low-NO3- conditions. The Cl--dependent resistance to low-N stress resulted from: more efficient use of the available NO3-; improved plant osmotic and water status regulation; improved stomatal conductance and photosynthetic rate; and better antioxidant response. We proposed that beneficial Cl- levels increase the crop ability to grow better with lower NO3- requirements and withstand N deficiency, promoting a more sustainable and resilient agriculture.

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