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PubMedDate not supplied

Erythrityl tetranitrate: sustained effects on systolic time intervals. changes consistent with sustained preload reduction.

The effects of sustained preload reduction have been demonstrated for several nitrates but not for erythrityl titranitrate. In seven patients with coronary heart disease, a randomized double-blind crossover clinical trial showed that chewable erthrityl tetranitrate, 10 mg, produced significant changes in systolic time intervals consistent with preload reduction and lasting for at least four hours. As compared with placebo, ejection time index (ETI) fell and remained significantly low between 6 and 90 minutes after administration, and pre-ejection period (PEP), isovolumic contraction time IVCT), and pre-ejection period/left ventricular ejection time (PEP/LVET) rose and remained significantly increased between 22 minutes and the four-hour endpoint. We conclude that erythrityl tetranitrate is a physiologically effective long-acting agents in patients with coronary heart disease.

Clinical Trials as Topic↗
PubMed2025

Sustainability in translational genomics research with undiagnosed patients: What is it, why do we need it, and how do we do it?

PURPOSE: Genomics research enrolling undiagnosed patients can provide answers for one-third of participants, and more can be diagnosed through future reanalysis. The long-term value for participants has raised questions of the sustainability of these studies, but the meaning, goals, and best practices for sustainability remain unclear. METHODS: We conducted semistructured interviews with researchers leading studies enrolling undiagnosed patients in the United States and Canada and used thematic content analysis to summarize key themes. RESULTS: Researchers lacked consensus regarding what sustainability was actually intended to sustain, variably referencing study procedures, personnel, data access, and participant recontact. However, the primary driver of sustainability was widely shared as the perceived obligation to continue to search for answers for undiagnosed participants. Proposed sustainability strategies included diversifying funding sources, developing centralized data infrastructure, and building collaborations across disciplines and institutions. Researchers also emphasized the need to address ethical concerns, to integrate research with clinical care, and for leadership from research funders to guide these efforts. CONCLUSION: Although genomics researchers perceived continued obligations to undiagnosed participants, they also lacked a shared understanding of the goals of sustainability and called for coordinated efforts to develop centralized infrastructure that integrated research and clinical care.

Humans↗
PubMed2025

Problematic use of sustainability claims in recent scientific literature on crop gene technologies: toward improving practices and communication.

There is growing interest in the role of agricultural genomics, including biotechnology, in enhancing the "sustainability" of food production systems. However, as "sustainability" becomes more frequently linked to the goals of agricultural genomics, a critical question arises: what claims are made about "sustainability" and how is the concept of "sustainability" defined in the scholarly literature on agricultural genomics? Using a structured analysis of the recent scientific literature, this article investigates increasingly frequent claims about "sustainability," including how this term is defined and measured in the field of agricultural genomics. It argues that more transparent definitions and clearer metrics, tied to appropriate scholarly literature, are crucial for improving the coherence, impact, and credibility of research in agricultural genomics.

Crops, Agricultural↗
PubMed1979

Comparative bioavailability of sustained-release and conventional tablets of hydroxyethyltheophylline in man.

The comparative bioavailability of sustained-release and conventional tablets of hydroxyethyltheophylline was studied in normal subjects. In a single dose study on 7 subjects, 3 conventional tablets or 2 sustained-release tablets were administered orally after a light breakfast and blood samples taken for 6 and 12 hours respectively. With conventional tablets the mean peak concentration (8.10 +/- 0.751 microgram/ml) was reached at 3 hours and concentrations less than 5 microgram/ml were observed in 4 out of 7 subjects at 6 hours. In contrast, with sustained-release tablets of theophylline and hydroxytheophylline complex the mean peak concentration (8.90 +/- 0.88 microgram/ml) was reached at 6 hours and levels above 5 microgram/ml were observed in 4 out of 7 cases at 12 hours. Administration of 2 sustained-release tablets twice a day produced trough plasma concentrations varying between 6.9-13.8 microgram/ml, i.e. within the therapeutic range in all the 5 subjects. It is concluded that this new oral sustained-release preparation provides therapeutic plasma theophylline concentration on a 12 hourly dosage schedule.

Biological Availability↗
PubMed2026

Microbial partnerships and molecular mechanisms in plant stress physiology for climate-resilient and sustainable farming.

Plant-microbial partnerships and their underlying molecular mechanisms are indispensable, natural drivers of improved nutrient acquisition and stress tolerance in the face of climate-driven environmental challenges. Modern multi-omics tools, when coupled with artificial intelligence and synthetic biology, enable the precise design of targeted bioinoculants and synthetic microbial consortia. Translating these advanced microbiome-based strategies into scalable, field-level agricultural applications provides a sustainable path toward securing global food production while maintaining soil health. Global climate change imposes multifaceted abiotic and biotic stresses on crops, disrupting physiological and molecular processes and threatening agricultural productivity. Plant-associated microbes represent an underexplored yet powerful ally in enhancing crop resilience. This review presents current knowledge of plant-microbe interactions and the molecular mechanisms governing plant stress physiology, with an emphasis on climate-resilient and sustainable farming. Hence, ever-changing environmental cues pose a significant burden on agricultural productivity, and plant-associated microbial communities modulate a cascade of physiological and molecular responses, including production of phytohormones, signaling, regulation of reactive oxygen species homeostasis, and activation of plant immune responses to help plants withstand stress and enhance productivity. Moreover, root exudates, phytohormones, and quorum sensing mediate the central communication networks, facilitating plant-microbe cross talk. Additionally, the advances in OMICs approaches aid in disentangling the molecular underpinnings of these interactions by providing mechanistic insights and potential candidate gene targets for crop improvement and stress resilience. In the post-genomic era, integrating artificial intelligence and big data analysis to optimize microbiome-based strategies for sustainable agriculture is a new frontier for disentangling plant-microbe symbiosis to improve soil health, enhance crop yields, and improve stress tolerance. Thus, by integrating the ecological, physiological, and molecular perspectives, this review highlights the transformative potential of harnessing plant-microbe symbiosis for climate-resilient and sustainable agriculture.

Stress, Physiological↗
PubMed1978

Pharmacokinetics of ordinary and sustained-release lithium carbonate in manic patients after acute dosage.

An ordinary and a sustained-release lithium carbonate preparation were administered acutely at equivalent dosage (1.80 g = 24.3 mmol) in a crossover fashion to manic patients. Serum lithium levels were determined by atomic absorption spectroscopy and pharmacokinetic parameters were calculated. Maximum mean serum levels of 1.13 mmol/l and 0.78 mmol/l were achieved at 6 h and 12 h respectively with the ordinary and sustained-release forms. The mean half-lives of absorption, redistribution and elimination were 0.78 h +/- 0.05 (SE), 5.06 h +/- 0.23, 26.8 h +/- 4.5 and 3.73 h +/- 0.37 (SE), 4.42 h +/- 0.28 and 25.6 h +/- 5.5 for the ordinary and sustained-release forms respectively. In healthy volunteers the ordinary preparation was completely absorbed but only 85% of the sustained-release form was absorbed in the manic subjects. Lithium ion distributed into two kinetic compartments and the final compartment appeared to correspond to total body water.

Bipolar Disorder↗
PubMed1977

Comparative bioavailability of a sustained release preparation of amitriptyline and conventional tablets.

A sustained release preparation of amitriptyline has been compared with conventional tablets in eight healthy human volunteers. The tablet produced a distinct peak in serum concentration shortly after administration, whereas the sustained release preparation caused a slow rise to a plateau. The maximum serum concentration and the time of its occurrence differed significantly between the two preparations. The differences between the serum concentration curves of the two preparations can be explained on the basis of a two compartment model of amitriptyline pharmacokinetics and from a difference in the absorption rate. The similar clinical effect obtained with a lower daily dose of the sustained release preparation than of the tablet cannot be accounted for in terms of pharmacokinetics. It is possible that a single evening dose of sustained release amitriptyline gives a more appropriate serum concentration profile of amitriptyline and its active metabolite nortriptyline than a conventional tablet taken three times a day.

Adult↗
PubMed2026

Plant-derived and microbial biostimulants in sustainable agriculture: mechanisms, applications, and challenges.

Plant biostimulants have emerged as transformative and sustainable tools for improving crop productivity, resource-use efficiency, and resilience under rapidly intensifying environmental stresses. Unlike conventional agrochemicals, biostimulants function by activating physiological, biochemical, and molecular processes that optimize plant performance without directly supplying nutrients or exerting pesticidal effects. This review comprehensively examines the integrated roles of plant-derived and microbial biostimulants in sustainable agriculture, with particular emphasis on microbial-mediated mechanisms underlying plant stress adaptation and rhizosphere functioning. Plant-derived biostimulants, including seaweed extracts, humic substances, protein hydrolysates, amino acids, and chitosan, enhance nutrient acquisition, root architecture, hormonal regulation, and antioxidant defense systems. More importantly, microbial biostimulants, such as plant growth-promoting rhizobacteria (PGPR), endophytic microorganisms, mycorrhizal fungi, actinomycetes, yeasts, and cyanobacteria, exert multifunctional effects through biological nitrogen fixation, mineral solubilization, phytohormone biosynthesis, volatile signaling, osmolyte accumulation, pathogen suppression, and modulation of stress-responsive genes. These beneficial microorganisms reshape rhizosphere microbial communities, improve nutrient cycling, and enhance plant tolerance to drought, salinity, heat, and heavy metal toxicity. Emerging evidence from genomics, transcriptomics, metabolomics, and microbiome-based investigations has further revealed the molecular networks and signaling pathways governing biostimulant-induced resilience and plant-microbe interactions. Despite their substantial promise, inconsistent field performance, formulation instability, regulatory limitations, and inadequate mechanistic understanding continue to restrict their large-scale adoption. This review highlights recent advances in microbial and plant-derived biostimulants while identifying critical knowledge gaps and future opportunities for precision biostimulant engineering, microbiome manipulation, and climate-resilient crop management. The integration of next generation biostimulant technologies into sustainable agricultural systems may significantly reduce dependence on agrochemicals while improving crop productivity, environmental sustainability, and global food security.

Agriculture↗
PubMed2026

Phase-resolved functional lung MRI detects single-dose and sustained bronchodilator responses in COPD in a randomized crossover trial.

OBJECTIVES: To evaluate the effects of tiotropium/olodaterol (T/O) on phase-resolved functional lung (PREFUL) MRI parameters in hyperinflated chronic obstructive pulmonary disease (COPD) patients and examine correlations with conventional cardiopulmonary and hyperpolarized 129Xe MRI measures. MATERIALS AND METHODS: Retrospective subanalysis of a prospective, randomized, placebo-controlled, crossover trial with open-label extension. Thirty-two patients with moderate-to-severe COPD (61.5&#x2009;&#xb1;&#x2009;7.7 years; 17 men); 30 completed the MRI extension at 1.5&#x2009;T. PREFUL analysis yielded regional ventilation (RVent), flow-volume loop correlation metric (FVL-CM), normalized perfusion (QN), ventilation defect percentage (VDP), perfusion defect percentage (QDP), V/Q match metrics (VQM), and pulmonary pulse wave velocity (PWV; post-hoc parameter). Linear mixed-effects models tested treatment effects; correlations were evaluated with Spearman's rank and bootstrap 95% confidence intervals (95% CIs). RESULTS: PREFUL parameters improved after T/O single dose (SD) versus placebo, including improvements in FVL-CM by 4.1 percentage points (pp; 95% CI: 1.0 to 7.3 pp) and QN by 0.4 pp (95% CI: 0.2 to 0.6 pp) and reductions in VDP and QDP, with parallel gains in VQM(Non-Defect) (p&#x2009;<&#x2009;0.05). PWV decreased after multiple doses (-0.87&#x2009;m/s, 95% CI: -1.26 to -0.48&#x2009;m/s). PREFUL MRI baseline values showed significant correlations with pulmonary function tests, cardiac, dynamic contrast-enhanced and 129Xe MRI. SD treatment-induced absolute changes in VDP(FVL-CM) correlated with reductions in residual volume (&#x3c1;&#x2009;=&#x2009;0.41, 95% CI: 0.02 to 0.64). Further correlations were observed between PREFUL MRI and &#xb9;&#xb2;&#x2079;Xe-derived VDP, apparent diffusion coefficient, and compartment ratios. CONCLUSION: PREFUL MRI sensitively captured immediate SD T/O-induced improvements in V/Q parameters and dose-dependent PWV responses after sustained bronchodilation. KEY POINTS: Question Can phase-resolved functional lung (PREFUL) MRI sensitively capture immediate single-dose and sustain multi-dose effects of tiotropium/olodaterol on ventilation-perfusion and vascular function in COPD patients? Findings Tiotropium/olodaterol improved PREFUL MRI-derived ventilation, perfusion, and V/Q matching parameters after a single dose, with sustained pulmonary vascular improvements after repeated dosing. Clinical relevance PREFUL MRI detected immediate and sustained functional improvements after tiotropium/olodaterol and showed significant correlations with cardiopulmonary tests and hyperpolarized &#xb9;&#xb2;&#x2079;Xe MRI, supporting its role as a sensitive, radiation-free tool for monitoring COPD treatment response.

Humans↗
PubMed1978

Human auditory sustained potentials. II. Stimulus relationships.

The auditory sustained potential recorded from the human scalp increases in amplitude with increasing stimulus intensity. At rapid rates of stimulus presentation its amplitude decreases but proportionately less so than the amplitude of the transient onset auditory evoked potential. The frequency specificity of this rate effect is complex, suggesting that there may be two underlying components of the scalp-recorded auditory sustained potential. The amplitude of the auditory sustained potential is smaller when the tonal frequency of the stimulus is higher. With prolonged stimulus durations there is some adaptation of the amplitude of the auditory sustained potential. This potential is larger in amplitude when sounds are presented binaurally than monaurally, and has a symmetrical coronal scalp distribution that is unaffected by the ear of stimulation.

Acoustic Stimulation↗
PubMed1979

Auditory evoked transient and sustained potentials in the human EEG: I. Effects of expectation of stimuli.

The characteristics of auditory evoked transient and sustained potentials were recorded using trains of four-tone stimuli of 1-second duration (interstimulus interval = 1 second) presented once every minute. The subject either attentively expected the stimuli or ignored them while reading. The electroencephalogram was recorded from derivations Cz-Al and Fz-Al. Expectation of the stimuli was associated with increased amplitudes of the transient responses both at the first stimulus of the train and during stimulus repetition. In contrast, the sustained potential at the first stimulus of the train was unchanged or smaller when the subject expected the stimuli. During stimulus repetition, however, the amplitude of the potential was enhanced by expectation of the stimuli. The results support the hypothesis of two sustained potential components and stress the importance of stimulus repetition rate when sustained potentials are studied.

Acoustic Stimulation↗
PubMed1979

Auditory evoked transient and sustained potentials in the human EEG: II. Effects of small doses of ethanol.

The effect of small doses of ethanol (0.4 g/kg) on auditory evoked transient and sustained potentials was studied. Tones of 1-second duration were presented in trains of four stimuli (interstimulus interval = 1 second; intertrain interval = 1 minute). The electroencephalogram was recorded from derivation Cz-Al. Ethanol depressed the transient responses both at the first stimulus of the train and during repeated stimuli. The sustained potentials elicited by the first stimuli of the train were not affected by ethanol, whereas the sustained potentials elicited by repeated stimuli were larger in amplitude under the influence of ethanol than during control experiments. It is suggested that the decrease of the transient responses under the influence of ethanol is mainly due to depression of the reticular formation, whereas the increase of sustained potentials reflects ethanol-induced release of intracortical inhibition.

Acoustic Stimulation↗
PubMed2026

Sustainable dietary recommendations for the Spanish population.

BACKGROUND/OBJECTIVES: The 2030 Agenda for Sustainable Development highlights the urgent need for a profound transformation in food production and consumption to enhance both sustainability and human health. The aim of this study is to provide both the general population and food system stakeholders with the most comprehensive and current information available on healthy and sustainable dietary patterns, in the form of culturally adapted food-based guidelines. METHODS: We performed a systematic review of the scientific evidence published since 2019 on the association between main food groups consumption and the risk of developing chronic diseases and premature mortality to update the information provided by the Dietary Guidelines for Americans 2020-2025, which summarized previous evidence. With this information, we updated the servings recommended in the former dietary guidelines for Spain. Then, we considered the recommendations of the EAT-Lancet Commission for healthy diets within planetary boundaries, specific dietary habits and food production in Spain, and adjusted the servings per each group to consider these characteristics. RESULTS: A minimum intake of 5 servings of vegetables and fruits per day is recommended, which may be distributed in at least 3 servings of vegetables per day, and 2-3 servings of fruits per day. Cereal consumption is set at 3-6 servings per day, adjusted to individual energy needs and prioritizing whole grains, no more than 4 servings per day are advised in cases of caloric restriction. Plant-based foods are recommended as the primary protein source, with legumes incorporated into at least one main daily meal and consumed at a frequency of at least 4 servings per week, ideally up to daily. Nut consumption should reach at least 3 servings per week, up to one serving per day, choosing those without added salt, fats or sugar. The remaining protein portions may include fish (&#x2265;3 servings/week, prioritizing oily fish and low-impact species), eggs (up to 4/week), dairy (up to 3/day, with low-sugar and low-salt options), and meat (up to 3/week, emphasizing poultry and rabbit, and minimizing processed meats). Daily consumption of olive oil at main meals is recommended. CONCLUSIONS: The proposed Sustainable Dietary Recommendations can help improve the health and well-being of the Spanish population, while reducing the environmental impact.

Humans↗
PubMed2026

Open and sustainable AI: challenges, opportunities and the road ahead in the life sciences.

Artificial intelligence (AI) has seen transformative breakthroughs in the life sciences, expanding possibilities to interpret biological information at an unprecedented capacity. To maximize return on growing investments and accelerate progress, it is urgent to address long-standing research challenges arising from the rapid adoption of AI methods. We review the erosion of trust in AI outputs driven by poor reusability and reproducibility, and highlight their impact on environmental sustainability. Furthermore, we discuss the fragmented components of the AI ecosystem and lack of guiding pathways to support open and sustainable AI model development. In response, this Perspective introduces practical open and sustainable AI recommendations mapped to over 300 ecosystem components and provides guiding implementation pathways. Our work connects researchers with relevant AI resources, facilitating the implementation of sustainable, reusable and reproducible AI. Built upon community consensus and aligned to existing efforts, these outputs will aid future policy development and structured pathways for guiding AI implementation.

Artificial Intelligence↗
PubMed2026

A scalable HPC framework for bioinformatics in resource-limited settings: design principles, implementation, and sustainability from the UVRI experience.

MOTIVATION: Building and sustaining High-Performance Computing (HPC) infrastructure for bioinformatics research in resource-limited settings presents significant technical, financial and operational challenges. Institutions in low-and middle-income regions often face constraints such as limited technical expertise, unstable infrastructure and restricted funding which can hinder the deployment of large-scale computational platforms necessary for modern genomics and bioinformatics analyses. RESULTS: We present a scalable and modular HPC framework developed at the Uganda Virus Research Institute (UVRI) to support large-scale genomics and other omics data analyses in resource-limited settings. The framework integrates open-source HPC management tools, infrastructure automation, and reproducible configuration management to enable reliable deployment and maintenance. Optimized storage and networking configurations combined with a phased capacity-building strategy support high-throughput genomic workflows while strengthening local technical expertise. From our implementation experience, we derive ten practical design and operational rules that provide a transferable methodology for establishing and sustaining in-house HPC infrastructure. These rules emphasize strategic investment in human capacity, structured planning, leveraging collaborations, adoption of open-source technologies and service management practices to improve operational resilience and long-term sustainability. AVAILABILITY: The design principles, automation strategies and implementation guidelines described in this work are applicable to institutions seeking to establish sustainable HPC resources for bioinformatics research in resource-constrained environments.

Computational Biology↗
PubMed2026

Simmondsia chinensis (jojoba) cake fermentation: A new, sustainable technology for advanced skin and scalp care ingredients.

OBJECTIVE: Simmondsia chinensis is a well-known commercially popular plant from which jojoba oil is extracted. Jojoba cake is a sustainably produced, intractable by-product of the jojoba seed oil extraction currently used principally as a fertilizer or burned as fuel. Fermentation work conducted with various microorganisms, including Lactobacillus plantarum, Saccharomyces cerevisiae and Streptococcus thermophilus, sustainably grown on aqueous jojoba cake fermented the cake, liberating jojoba-based amino acids, peptides and proteins. The ferments have been examined chemically and via in&#xa0;vitro cell and tissue studies to develop new skin and scalp care targeted ingredients. METHODS: The jojoba cake contained nutrients (proteins, sugars and lipids) that self-sustain aqueous bacterial fermentation. The ferments were examined on 3D tissue models in&#xa0;vitro via human genomic microarrays. A ferment produced by Lactobacillus plantarum was further tested in&#xa0;vitro using ELISA protein assays on skin cell cultures. A 56-day clinical study on 46 individuals examined the influence of 1.0% of the Lactobacillus ferment on collagen expression using Diffuse Reflectance Spectroscopy (DRS). RESULTS: Gene responses were measured on 244+ genes known to have skin functions. It was found that the Lactobacillus ferment showed the greatest upregulation of skin-associated genes, and three highly upregulated proteins were examined more closely in&#xa0;vitro using ELISA protein assays: collagen-1A1, protocadherin-18 and opioid growth factor receptor. Each protein was upregulated in a dose-dependent fashion. The collagen analysis by DRS demonstrated a statistically significant increase in collagen fluorescence on Day 28 and Day 56 compared to baseline and placebo cream. Further mapping of the collagen fluorescence was done on the individuals using the active formulation at Days 0, 28 and 56. CONCLUSION: Jojoba cake presents a new source of sustainably grown biomass, but the cake is not suitable for topical applications. Fermentation produces components more suitable for topical care. In&#xa0;vitro studies demonstrated upregulation of three skin proteins associated with healing skin. Further studies also employed a newly emerging spectroscopic technique to measure collagen fluorescence in the skin in&#xa0;vivo, the results supporting in&#xa0;vitro work indicating the ferment made with Lactobacillus was able to stimulate collagen synthesis in the skin.

Lactobacillus↗
PubMed1979

Pharmacodynamic and spirometric responses to a sustained-release theophylline capsule.

A prolonged therapeutic effect following a single oral dose of theophylline and maintenance of an adequate therapeutic blood level of theophylline is an important factor in the management of chronic bronchial asthma. Eighteen adult asthmatics, nine of whom were females and nine males, aged between 21-53 years, were given a sustained release theophylline capsule, 250 mg, every 12 hours and pulmonary mechanical functions as well as serum theophylline levels were studied. All patients received Elixophyllin Elixir, 250 mg, and their serum level as well as pulmonary functions were studied and compared to those after receiving the sustained release capsules. In these patients, after isoproterenol inhalation, an average of 25.6% improvement in FEV1 was observed while after placebo there were very minimum changes. At the steady-state of sustained release theophylline capsule administration, an average of 20% improvement of FEV1 was observed at the five hour period and sufficient bronchodilation expressed as FEV1 was observed for a 10-12 hour period. Indeed, a sustained release theophylline capsule fulfilled the requirement that it adequately maintained therapeutic theophylline level of the blood and improved bronchodilation lasting up to 12 hours.

Adult↗