Impacts of Bacillus amyloliquefaciens and Trichoderma spp. on Pac Choi (Brassica rapa var. chinensis) grown in different hydroponic systems.

Soilless production systems (i.e hydroponics, aeroponics, aquaponics) have become commonplace in urban settings and controlled environments. They are efficient nutrient recyclers, space savers, and water conservers. However, they lack high levels of biological richness in the root microbiome when compared to soil production systems, which may affect plant health and nutrient uptake. To address this issue and incorporate more sustainable practices, beneficial microorganisms (i.e. Trichoderma spp., Bacillus sp.) can be added in the form of biofertilizers. However, many factors affect impacts of microorganisms and their interactions with plants. In this experiment, Black Summer Pac Choi (Brassica rapa var. Chinensis) was grown for two trials in a Deep-Water system (DWS) or a Nutrient Film Technique system (NFT) with commercial biofertilizers containing Trichoderma spp., Bacillus amyloliquefaciens, a combination of both, and a control. Plant physiology, nutrient composition, and nutrient uptake efficiency (NUE) were generally negatively affected by Trichoderma spp. both growing systems, indicating that Trichoderma may not be recommended for hydroponic production. However, Bacillus amyloliquefaciens showed promise as an effective biofertilizer in the NFT systems and had a positive influence on NUE in DWS.

Prognostic Value of Echocardiographic Coupling Metrics in Systemic Sclerosis-Associated Pulmonary Vascular Disease.

BACKGROUND: Ineffective right ventricular (RV) adaptation to increasing pulmonary arterial (PA) afterload in pulmonary vascular disease (PVD) significantly contributes to morbidity and mortality. PVD in systemic sclerosis (SSc) arises through various mechanisms, yet detecting abnormal contractile response remains challenging. Here, we examine whether echocardiographic RV-PA coupling metrics correlate with invasive pressure-volume (PV) loops, enhancing the prediction of adverse clinical outcomes in SSc-PVD patients. METHODS: Prospectively enrolled patients with SSc-PVD with paired echocardiogram and PV loops were included. Linear regression and receiver-operating curve (ROC) analysis were used to assess the relationship between tricuspid annular plane systolic excursion (TAPSE)/PA systolic pressure (PASP), fractional area change (FAC)/PASP, tissue Doppler velocity (TDI S')/PASP, RV free wall strain (RVFWS)/PASP and coupling thresholds defined by end-systolic to end-arterial elastance (Ees/Ea), obtained by the multi-beat method. The contribution of right atrial strain (RAS) to RV-PA coupling parameters was also investigated. Kaplan-Meier analysis was used to identify the relationship between coupling ratios and composite outcomes including clinical worsening, lung transplant, and death. RESULTS: 42 patients with SSc were studied with mean age 59 ± 12 years, 91% female and varying degrees of PVD: mPAP 29.5 ± 12.8 mmHg, PVR 4.7 ± 4.2 WU, PCWP 10.3 ± 4.1 mmHg. Echocardiographic coupling metrics including TAPSE/PASP, FAC/PASP, TDI S'/PASP, RVFWSglobal and RVFWSbasal/PASP, and RASreservoir/PASP were linearly associated with Ees/Ea. At cut-points obtained through ROC analysis, all ratios were predictive of RV-PA uncoupling, defined by Ees/Ea, and composite outcomes. Additionally, RASreservoir/RVFWS correlated with Ees/Ea even after adjustment for PASP, suggesting that diminished RAS further impacts RV performance and coupling. CONCLUSION: Echocardiographic RV-PA coupling ratios strongly correlate with invasive Ees/Ea and predict adverse clinical outcomes in SSc patients across the spectrum of PVD. Further, we demonstrate how RAS impacts RV performance. These findings may refine risk stratification and prognostication in this at-risk cohort.

Effect of Summer Holiday Programs on Children's Mental Health and Well-Being: Systematic Review and Meta-Analysis.

Poor youth mental health is an area of global concern. Summer holiday programs may provide environments that support mental health when the structures and supports of school are not available. The aim of this review was to determine the effectiveness of summer holiday programs in improving the mental health, social-emotional well-being, and cognitive (non-academic) outcomes of children and adolescents. Studies of summer holiday programs for school-aged children (5-18 years) were included if they measured any mental, socio-emotional or cognitive (non-academic) outcome. Studies were excluded if they were published prior to 2000, targeted clinical populations or lasted less than five days. Six databases were searched (April 2023). Risk of bias was assessed using the PEDro tool. Study outcomes were grouped according to three main constructs: mental health (psychological well-being, anxiety, depression, distress, and self-perception including self-esteem, self-worth, self-concept, confidence, and competence); social-emotional well-being (behavior and social skills, e.g., communication, bullying, conflict resolution, empathy, and social skills); and cognitive function (memory, selective attention, and executive function). A fourth "other" group captured substance use, personality traits, character skills, and values. Effect sizes were calculated as the standardized mean difference between pre- and post-intervention scores. The synthesis involved a random-effects meta-analysis (presented in forest plots), where possible, with the remaining outcomes narratively synthesized. Twenty-six studies (n = 6812 participants) were included. The results of the meta-analysis suggested that summer programs showed a statistically non-significant trend toward reducing symptoms of anxiety and depression (k = 2 studies, SMD = -0.17, 95% CI -2.94, 2.60), psychological distress (k = 2 studies, SMD -0.46, 95% CI -1.71, 0.79), and no effect on self-esteem (k = 6 studies, SMD = 0.02, 95% CI -0.02, 0.06) or self-worth (k = 3 studies, SMD = 0.05, 95% CI 0.00, 0.11). Narrative syntheses indicated a pattern toward improvements in general mental health, self-perception, social-emotional outcomes, and cognition. Studies were generally small, with a high risk of bias. Summer holiday programs for children and adolescents show trends toward improving mental, social, emotional, and cognitive outcomes. Programs targeting disadvantaged children showed stronger patterns of improvement related to mental health and self-perception than programs targeting the general population. While effect sizes are small to negligible, they consistently indicate improvements. Summer programs present a promising avenue to promote mental health in children; however, further rigorously designed, clearly reported control-group studies are required to more fully understand their effects.

Real-World Accuracy of Wearable Activity Trackers for Detecting Medical Conditions: Systematic Review and Meta-Analysis.

BACKGROUND: Wearable activity trackers, including fitness bands and smartwatches, offer the potential for disease detection by monitoring physiological parameters. However, their accuracy as specific disease diagnostic tools remains uncertain. OBJECTIVE: This systematic review and meta-analysis aims to evaluate whether wearable activity trackers can be used to detect disease and medical events. METHODS: Ten electronic databases were searched for studies published from inception to April 1, 2023. Studies were eligible if they used a wearable activity tracker to diagnose or detect a medical condition or event (eg, falls) in free-living conditions in adults. Meta-analyses were performed to assess the overall area under the curve (%), accuracy (%), sensitivity (%), specificity (%), and positive predictive value (%). Subgroup analyses were performed to assess device type (Fitbit, Oura ring, and mixed). The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Diagnostic Test Accuracy Studies. RESULTS: A total of 28 studies were included, involving a total of 1,226,801 participants (age range 28.6-78.3). In total, 16 (57%) studies used wearables for diagnosis of COVID-19, 5 (18%) studies for atrial fibrillation, 3 (11%) studies for arrhythmia or abnormal pulse, 3 (11%) studies for falls, and 1 (4%) study for viral symptoms. The devices used were Fitbit (n=6), Apple watch (n=6), Oura ring (n=3), a combination of devices (n=7), Empatica E4 (n=1), Dynaport MoveMonitor (n=2), Samsung Galaxy Watch (n=1), and other or not specified (n=2). For COVID-19 detection, meta-analyses showed a pooled area under the curve of 80.2% (95% CI 71.0%-89.3%), an accuracy of 87.5% (95% CI 81.6%-93.5%), a sensitivity of 79.5% (95% CI 67.7%-91.3%), and specificity of 76.8% (95% CI 69.4%-84.1%). For atrial fibrillation detection, pooled positive predictive value was 87.4% (95% CI 75.7%-99.1%), sensitivity was 94.2% (95% CI 88.7%-99.7%), and specificity was 95.3% (95% CI 91.8%-98.8%). For fall detection, pooled sensitivity was 81.9% (95% CI 75.1%-88.1%) and specificity was 62.5% (95% CI 14.4%-100%). CONCLUSIONS: Wearable activity trackers show promise in disease detection, with notable accuracy in identifying atrial fibrillation and COVID-19. While these findings are encouraging, further research and improvements are required to enhance their diagnostic precision and applicability. TRIAL REGISTRATION: Prospero CRD42023407867; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=407867.

Multiple Biomarkers Are Equivalent to Clinical Pulmonary Arterial Hypertension Survival Risk Models.

BACKGROUND: Risk assessment in pulmonary arterial hypertension (PAH) is fundamental to guiding treatment and improved outcomes. Clinical models are excellent at identifying high-risk patients, but leave uncertainty amongst moderate-risk patients. RESEARCH QUESTION: Can a multiple blood biomarker model of PAH, using previously described biomarkers, improve risk discrimination over current models? STUDY DESIGN AND METHODS: Using a multiplex enzyme-linked immunosorbent assay, we measured N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP), soluble suppressor of tumorigenicity, IL-6, endostatin, galectin 3, HDGF, and insulin-like growth factor binding proteins (IGFBP1-7) in training (n = 1,623), test (n = 696), and validation (n = 237) cohorts. Clinical variables and biomarkers were evaluated by principal component analysis. NT-proBNP was not included to develop a model independent of NT-proBNP. Unsupervised k-means clustering classified participants into clusters. Transplant-free survival by cluster was examined using Kaplan-Meier and Cox proportional hazard regressions. Hazard by cluster was compared with NT-proBNP, Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL), and European Society of Cardiology (ESC) and European Respiratory Society (ERS) risk models alone and combined clinical and biomarker models. RESULTS: The algorithm generated 5 clusters with good risk discrimination using 6 biomarkers, weight, height, and age at PAH diagnosis. In the test and validation cohorts, the biomarker model alone performed equivalent to REVEAL (area under the receiver operating characteristic curve, 0.74). Adding the biomarker model to the ESC and ERS score and REVEAL score improved the ESC and ERS score and REVEAL score. The best overall model was the biomarker model adjusted for NT-proBNP with the best C statistic, Akaike information criterion, and calibration for the adjusted model compared with either the biomarker or NT-proBNP model alone. INTERPRETATION: A multibiomarker model alone was equivalent to current PAH clinical mortality risk prediction models and improved performance when combined and added to NT-proBNP. Clinical risk scores offer excellent predictive models, but require multiple tests; adding blood biomarkers to models can improve prediction or can enable more frequent, noninvasive monitoring of risk in PAH to support therapeutic decision-making.

An adult patient with pulmonary arterial hypertension, a NOTCH3 mutation, and leflunomide exposure.

Pulmonary arterial hypertension (PAH) is a poorly understood disease of the small pulmonary arteries. Pulmonary vascular remodeling and progressively rising pulmonary vascular resistance are hallmarks of the disease that ultimately result in right heart failure. Several genetic mutations, most notably in bone morphogenetic protein receptor type 2, have a causal association with heritable forms of PAH. Mutations in neurogenic locus notch homolog protein 3 (NOTCH3) have been reported in adults and children with PAH, but whether NOTCH3 is causally associated with PAH is debated. With this case report, we describe the clinical characteristics, comorbidities, and exposure history of an adult patient with PAH and multiple sclerosis who was found to have a NOTCH3 missense mutation and exposure to leflunomide.

Poor cardiac output reserve in pulmonary arterial hypertension is associated with right ventricular stiffness and impaired interventricular dependence.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterised by poor exercise tolerance. The contribution of right ventricular (RV) diastolic function to the augmentation of cardiac output during exercise is not known. This study leverages pressure-volume (P-V) loop analysis to characterise the impact of RV diastology on poor flow augmentation during exercise in PAH. METHODS: RV P-V loops were measured in 41 PAH patients at rest and during supine bike exercise. Patients were stratified by median change in cardiac index (CI) during exercise into two groups: high and low CI reserve. Indices of diastolic function (end-diastolic elastance (E ed)) and ventricular interdependence (left ventricular transmural pressure (LVTMP)) were compared at matched exercise stages. RESULTS: Compared to patients with high CI reserve, those with low reserve exhibited lower exercise stroke volume (36 versus 49 mL·m-2; p=0.0001), with higher associated exercise afterload (effective arterial elastance (E a) 1.76 versus 0.90 mmHg·mL-1; p<0.0001), RV stiffness (E ed 0.68 versus 0.26 mmHg·mL-1; p=0.003) and right-sided pressures (right atrial pressure 14 versus 8 mmHg; p=0.002). Higher right-sided pressures led to significantly lower LV filling among the low CI reserve subjects (LVTMP -4.6 versus 3.2 mmHg; p=0.0001). Interestingly, low exercise flow reserve correlated significantly with high afterload and RV stiffness, but not with RV contractility nor RV-PA coupling. CONCLUSIONS: Patients with poor exercise CI reserve exhibit poor exercise RV afterload, stiffness and right-sided filling pressures that depress LV filling and stroke work. High afterload and RV stiffness were the best correlates to low flow reserve in PAH. Exercise unmasked significant pathophysiological PAH differences unapparent at rest.

Chinese hamster ovary cell line engineering strategies for modular production of custom extracellular vesicles.

Continuously secreted by all cell types, extracellular vesicles (EVs) are small membrane-bound structures which shuttle bioactive cargo between cells across their external environment. Their central role as natural molecular messengers and ability to cross biological barriers has garnered significant attention in the use of EVs as therapeutic delivery vehicles. Still, harnessing the potential of EVs is faced with many obstacles. A cell line engineering approach can be used to exploit EVs to encapsulate a bespoke cargo of interest. However, full details regarding native EV-loading mechanisms remain under debate, making this a challenge. While Chinese hamster ovary (CHO) cells are well known to be the preferred host for recombinant therapeutic protein production, their application as an EV producer cell host has been largely overlooked. In this study, we engineered CHO DG44 cells to produce custom EVs with bespoke cargo. To this end, genetic constructs employing split green fluorescent protein technology were designed for tagging both CD81 and protein cargoes to enable EV loading via self-assembling activity. To demonstrate this, NanoLuc and mCherry were used as model reporter cargoes to validate engineered loading into EVs. Experimental findings indicated that our custom EV approach produced vesicles with up to 15-fold greater cargo compared with commonly used passive loading strategies. When applied to recipient cells, we observed a dose-dependent increase in cargo activity, suggesting successful delivery of engineered cargo via our custom CHO EVs.

Collagen 18A1/Endostatin Expression in the Progression of Right Ventricular Remodeling and Dysfunction in Pulmonary Arterial Hypertension.

Numerous studies have demonstrated that endostatin (ES), a potent angiostatic peptide derived from collagen type XVIII α 1 chain and encoded by COL18A1, is elevated in pulmonary arterial hypertension (PAH). It is important to note that elevated ES has consistently been associated with altered hemodynamics, poor functional status, and adverse outcomes in adult and pediatric PAH. This study used serum samples from patients with Group I PAH and plasma and tissue samples derived from the Sugen/hypoxia rat pulmonary hypertension model to define associations between COL18A1/ES and disease development, including hemodynamics, right ventricle (RV) remodeling, and RV dysfunction. Using cardiac magnetic resonance imaging and advanced hemodynamic assessments with pressure-volume loops in patients with PAH to assess RV-pulmonary arterial coupling, we observed a strong relationship between circulating ES levels and metrics of RV structure and function. Specifically, RV mass and the ventricular mass index were positively associated with ES, whereas RV ejection fraction and RV-pulmonary arterial coupling were inversely associated with ES levels. Our animal data demonstrate that the development of pulmonary hypertension is associated with increased COL18A1/ES in the heart as well as the lungs. Disease-associated increases in COL18A1 mRNA and protein were most pronounced in the RV compared with the left ventricle and lung. COL18A1 expression in the RV was strongly associated with disease-associated changes in RV mass, fibrosis, and myocardial capillary density. These findings indicate that COL18A1/ES increases early in disease development in the RV and implicates COL18A1/ES in pathologic RV dysfunction in PAH.

Growth of Romaine Lettuce in Eggshell Powder Mixed Alginate Hydrogel in an Aeroponic System for Water Conservation and Vitamin C Biofortification.

Vitamin C is crucial for physical well-being, and its deficiency can lead to severe health consequences. Biofortification has been used to address this deficiency by enhancing vitamin C in plants. Additionally, soilless agriculture has been used to conserve and optimize water use in comparison to conventional agriculture. While hydrogels have been shown to improve water conservation and are used for biofortification in crops, their application has only been explored in soil-based and hydroponic farming. The aeroponics system is a plant-growing method that has shown potential for increasing yields and biomass while conserving water and nutrients. In this paper, we have developed an aeroponic-compatible medium to grow romaine lettuce (Lactuca sativa L.) with eggshell powder (ESP) mixed with calcium-alginate hydrogel as a substrate and nutrient source aiming to conserve water and incorporate vitamin C through biofortification. Herein, lower water spray time and higher intervals, with varied gel types and ESP concentrations, resulted in healthy lettuce growth. Plants treated with 0.5% ascorbic acid-absorbed ESP-mixed alginate hydrogel for biofortification showed higher levels of vitamin C compared to the traditional method. This study suggests using an alginate hydrogel-ESP-based substrate in aeroponics to reduce water usage and enhance plant biofortification of vitamin C.

Aberrant long-chain fatty acid metabolism associated with evolving systemic sclerosis-associated pulmonary arterial hypertension.

We sought to investigate differential metabolism in patients with systemic sclerosis (SSc) who develop pulmonary arterial hypertension (PAH) versus those who do not, as a method of identifying potential disease biomarkers. In a nested case-control design, serum metabolites were assayed in SSc subjects who developed right heart catheterization-confirmed PAH (n = 22) while under surveillance in a longitudinal cohort from Johns Hopkins, then compared with metabolites assayed in matched SSc patients who did not develop PAH (n = 22). Serum samples were collected at "proximate" (within 12 months) and "distant" (within 1-5 yr) time points relative to PAH diagnosis. Metabolites were identified using liquid chromatography-mass spectroscopy (LC-MS). An LC-MS dataset from SSc subjects with either mildly elevated pulmonary pressures or overt PAH from the University of Michigan was compared. Differentially abundant metabolites were tested as predictors of PAH in two additional validation SSc cohorts. Long-chain fatty acid metabolism (LCFA) consistently differed in SSc-PAH versus SSc without PH. LCFA metabolites discriminated SSc-PAH patients with mildly elevated pressures in the Michigan cohort and predicted SSc-PAH up to 2 yr before clinical diagnosis in the Hopkins cohort. Acylcholines containing LCFA residues and linoleic acid metabolites were most important for discriminating SSc-PAH. Combinations of acylcholines and linoleic acid metabolites provided good discrimination of SSc-PAH across cohorts. Aberrant lipid metabolism is observed throughout the evolution of PAH in SSc. Lipidomic signatures of abnormal LCFA metabolism distinguish SSc-PAH patients from those without PH, including before clinical diagnosis and in mild disease.NEW & NOTEWORTHY Abnormal lipid metabolism is evident across time in the development of SSc-PAH, and dysregulated long-chain fatty acid metabolism predicts overt PAH.

Financial Incentives for Physical Activity and Sports Participation in Young People.

Physical inactivity is a global health problem. Childhood is an opportune time to establish healthy physical activity behaviors, including the participation in organized physical activity, such as sports. We hypothesize that financial incentives can improve young people's participation in physical activity and sports. The design of the incentive and the context in which it operates are crucial to its success.

A Three Delays theoretical framework to describe social determinants as barriers to dental care.

OBJECTIVES: The Three Delays model is a well-established global public health framework for the utilization of obstetric services where each delay represents a series of factors affecting utilization: (1) Delay #1-Deciding to seek care, (2) Delay #2-Reaching an appropriate facility and (3) Delay #3-Receiving adequate care. The aim of this qualitative study was to explore the application of the Three Delays model to dental service utilization and describe factors attributed to delayed utilization within this framework. METHODS: This study utilized a framework analysis, underpinned by the Three Delays model, to examine delays in dental care utilization. A criterion purposive sample of English-speaking adults (18+ years) in Massachusetts and Florida, USA with limited dental care access was recruited. Data were collected via semi-structured interviews conducted in two phases: 17 individual interviews, followed by interviews with a subset of five participants over 3 months (a total of 18 interviews). The analysis involved inductive thematic coding and systematic organization within the framework. RESULTS: Major themes and subthemes were constructed from the participants' narratives, identified and categorized as factors in the Three Delays framework. Each of the delays was interrelated to the other two, and Delay #1 was the most common delay based on the participants' interviews. The themes and subthemes contributing to one or more delays included interpersonal communication, prior dental experience, financial considerations, childcare costs, social connection, technology literacy, time constraints, competing priorities, stressors such as eviction and immigration status and microaggressions including racism and stigma. CONCLUSION: The Three Delays model was applicable to the study of dental care utilization and factors that impact the decision to seek dental care, reaching an appropriate dental facility and receiving adequate dental care in this study context.

Application of Metabolomics across the Spectrum of Pulmonary and Critical Care Medicine.

In recent years, metabolomics, the systematic study of small-molecule metabolites in biological samples, has yielded fresh insights into the molecular determinants of pulmonary diseases and critical illness. The purpose of this article is to orient the reader to this emerging field by discussing the fundamental tenets underlying metabolomics research, the tools and techniques that serve as foundational methodologies, and the various statistical approaches to analysis of metabolomics datasets. We present several examples of metabolomics applied to pulmonary and critical care medicine to illustrate the potential of this avenue of research to deepen our understanding of pathophysiology. We conclude by reviewing recent advances in the field and future research directions that stand to further the goal of personalizing medicine to improve patient care.

Fatty acid metabolism promotes TRPV4 activity in lung microvascular endothelial cells in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a morbid disease characterized by significant lung endothelial cell (EC) dysfunction. Prior work has shown that microvascular endothelial cells (MVECs) isolated from animals with experimental PAH and patients with PAH exhibit significant abnormalities in metabolism and calcium signaling. With regards to metabolism, we and others have shown evidence of increased aerobic glycolysis and evidence of increased utilization of alternate fuel sources (such as fatty acids) in PAH EC. In the realm of calcium signaling, our prior work linked increased activity of the transient receptor potential vanilloid-4 (TRPV4) channel to increased proliferation of MVECs isolated from the Sugen/Hypoxia rat model of PAH (SuHx-MVECs). However, the relationship between metabolic shifts and calcium abnormalities was not clear. Specifically, whether shifts in metabolism were responsible for increasing TRPV4 channel activity in SuHx-MVECs was not known. In this study, using human data, serum samples from SuHx rats, and SuHx-MVECs, we describe the consequences of increased MVEC fatty acid oxidation in PAH. In human samples, we observed an increase in long-chain fatty acid levels that was associated with PAH severity. Next, using SuHx rats and SuHx-MVECs, we observed increased intracellular levels of lipids. We also show that increasing intracellular lipid content increases TRPV4 activity, whereas inhibiting fatty acid oxidation normalizes basal calcium levels in SuHx-MVECs. By exploring the fate of fatty acid-derived carbons, we observed that the metabolite linking increased intracellular lipids to TRPV4 activity was ß-hydroxybutyrate (BOHB), a product of fatty acid oxidation. Finally, we show that BOHB supplementation alone is sufficient to sensitize the TRPV4 channel in rat and mouse MVECs. Returning to humans, we observe a transpulmonary BOHB gradient in human patients with PAH. Thus, we establish a link between fatty acid oxidation, BOHB production, and TRPV4 activity in MVECs in PAH. These data provide new insight into metabolic regulation of calcium signaling in lung MVECs in PAH.NEW & NOTEWORTHY In this paper, we explore the link between metabolism and intracellular calcium levels in microvascular endothelial cells (MVECs) in pulmonary arterial hypertension (PAH). We show that fatty acid oxidation promotes sensitivity of the transient receptor potential vanilloid-4 (TRPV4) calcium channel in MVECs isolated from a rodent model of PAH.

Simultaneous biofortification of vitamin C and mineral nutrients in arugula microgreens.

Microgreens have shown promise in improving the overall nutritional value of diets due to their high nutrient density. Agronomic biofortification, is an efficient strategy for enhancing the nutritional value of crops, including microgreens. This study aimed to biofortify vitamin C and other essential nutrients in arugula microgreens using four treatments containing 0.25 % ascorbic acid, pH adjusted with different bases: KOH, Ca(OH)2, ZnCO3, or NaOH and a deionized water control. The results indicate that ascorbic acid-treated microgreens had more vitamin C, greater fresh weight and % dry matter than the control. The ascorbic acid + Zn treatment had an 135 % average increase in vitamin C compared to the control. Microgreens treated with ascorbic acid also showed increased levels of minerals that are present in the nutrient solution, such as potassium, sodium, calcium, and zinc. This research contributes to the growing interest in microgreens biofortification and their role in addressing multi-nutrient deficiencies.

A decade of improving nutritional quality of horticultural crops agronomically (2012-2022): A systematic literature review.

The ultimate goal of world crop production is to produce more with less to meet the growing population demands. However, concentrating solely on increased quantity of production often impacts the quality of produce. Consumption of crops or foods that do not meet nutritional or dietary needs can lead to malnutrition. Malnutrition and undernutrition are prevalent in a significant portion of the population. Agronomic biofortification of minerals and vitamins in horticultural crops has emerged as a promising approach to address nutrient deficiencies and enhance the nutritional quality of food. Despite numerous research papers on plant nutrient biofortification, there remains a lack of systematic reviews that comprehensively summarize the latest knowledge on this topic. Herein we discuss different agronomic ways to biofortify several horticultural crops over the past decade. This systematic review aims to fill this gap by presenting various methodologies and comparing the outcomes of these methods in respect to nutrient content in plant parts. The review focuses on original research papers collected from various scientific databases including Scopus and Web of Knowledge, covering the most recent literature from the last ten years (2012-2022) for specific studies on the agronomic biofortification macronutrients, micronutrients, and vitamins in horticultural plants with exclusion of certain criteria such as 'genetic,' 'breeding,' and 'agronomic crops.' This review critically analyzes the current state of research and explores prospects for the future in this field. The biofortification of various minerals and vitamins, including calcium, selenium, iodine, B vitamins, vitamin A, and vitamin C, are examined, highlighting the achievements and limitations of existing studies. In conclusion, agronomic biofortification of minerals and vitamins in horticultural crops with further research offers a promising approach to address nutrient deficiencies and improve the nutritional quality of food.

Kynurenine pathway metabolism evolves with development of preclinical and scleroderma-associated pulmonary arterial hypertension.

Understanding metabolic evolution underlying pulmonary arterial hypertension (PAH) development may clarify pathobiology and reveal disease-specific biomarkers. Patients with systemic sclerosis (SSc) are regularly surveilled for PAH, presenting an opportunity to examine metabolic change as disease develops in an at-risk cohort. We performed mass spectrometry-based metabolomics on longitudinal serum samples collected before and near SSc-PAH diagnosis, compared with time-matched SSc subjects without PAH, in a SSc surveillance cohort. We validated metabolic differences in a second cohort and determined metabolite-phenotype relationships. In parallel, we performed serial metabolomic and hemodynamic assessments as the disease developed in a preclinical model. For differentially expressed metabolites, we investigated corresponding gene expression in human and rodent PAH lungs. Kynurenine and its ratio to tryptophan (kyn/trp) increased over the surveillance period in patients with SSc who developed PAH. Higher kyn/trp measured two years before diagnostic right heart catheterization increased the odds of SSc-PAH diagnosis (OR 1.57, 95% CI 1.05-2.36, P = 0.028). The slope of kyn/trp rise during SSc surveillance predicted PAH development and mortality. In both clinical and experimental PAH, higher kynurenine pathway metabolites correlated with adverse pulmonary vascular and RV measurements. In human and rodent PAH lungs, expression of TDO2, which encodes tryptophan 2,3 dioxygenase (TDO), a protein that catalyzes tryptophan conversion to kynurenine, was significantly upregulated and tightly correlated with pulmonary hypertensive features. Upregulated kynurenine pathway metabolism occurs early in PAH, localizes to the lung, and may be modulated by TDO2. Kynurenine pathway metabolites may be candidate PAH biomarkers and TDO warrants exploration as a potential novel therapeutic target.NEW & NOTEWORTHY Our study shows an early increase in kynurenine pathway metabolism in at-risk subjects with systemic sclerosis who develop pulmonary arterial hypertension (PAH). We show that kynurenine pathway upregulation precedes clinical diagnosis and that this metabolic shift is associated with increased disease severity and shorter survival times. We also show that gene expression of TDO2, an enzyme that generates kynurenine from tryptophan, rises with PAH development.

Treating acute exacerbations of COPD with Chinese herbal medicine to aid antibiotic use reduction (Excalibur): a randomised double-blind, placebo-controlled feasibility trial.

Background: Although many acute exacerbations of COPD (AECOPD) are triggered by non-bacterial causes, they are often treated with antibiotics. Preliminary research suggests that the Chinese herbal medicine "Shufeng Jiedu" (SFJD), may improve recovery and therefore reduce antibiotic use in patients with AECOPD. Aims: To assess the feasibility of conducting a randomised placebo-controlled clinical trial of SFJD for AECOPD in UK primary care. Methods: GPs opportunistically recruited patients experiencing an AECOPD. Participants were randomised 1:1 to usual care plus SFJD or placebo for 14 days. Participants, GPs and research nurses were blinded to treatment allocation. GPs could prescribe immediate, delayed or no antibiotics, with delayed prescribing encouraged where appropriate. Participants were asked to complete a participant diary, including EXACT-PRO and CAT™ questionnaires for up to 4 weeks. Outcomes included recruitment rate and other measures of study feasibility described using only descriptive statistics and with no formal comparisons between groups. We also conducted qualitative interviews with recruited and non-recruited COPD patients and clinicians, analysed using framework analysis. Results: Over 6 months, 19 participants (6 SFJD, 13 placebo) were recruited. Sixteen (84%) participants returned diaries or provided a diary by recall. Overall, 1.3 participants were recruited per 1,000 patients on the COPD register per month open. Median duration of treatment was 9.8 days in the intervention group vs 13.3 days in the placebo group. The main reason for discontinuation in both groups was perceived side-effects. in both groups. Point estimates for both the EXACT-PRO and CAT™ outcomes suggested possible small benefits of SFJD. Most patients and clinicians were happy to try SFJD as an alternative to antibiotics for AECOPD. Recruitment was lower than expected because of the short recruitment period, the lower incidence of AECOPD during the COVID-19 pandemic, patients starting antibiotics from "rescue packs" before seeing their GP, and workforce challenges in primary care. Conclusion: Recruitment was impaired by the COVID-19 pandemic. Nevertheless, we were able to demonstrate the feasibility of recruiting and randomising participants and identified approaches to address recruitment challenges such as including the trial medication in COPD patients' "rescue packs" and delegating recruitment to a central trials team. Clinical Trial Registration: Identifier, ISRCTN26614726.