This study investigates the potential of Pythium oligandrum (strains M1 and 00X48) as a biocontrol agent in suppressing the growth of Fusarium culmorum and the production of mycotoxins during the ...malting of naturally contaminated barley (Hordeum vulgare). The effects of the biocontrol agent on F. culmorum-infected barley malt (BM) were evaluated through real-time PCR and its impact on mycotoxin production was determined by quantitative analysis of deoxynivalenol (DON) and deoxynivalenol-3-glucoside (D3G). The effect of treatment on BM and beer quality were also determined through European Brewery Convention (EBC) standard methods. Optimal treatment with P. oligandrum strains M1 and 00X48 yielded a 59% and 48% reduction in F. culmorum contamination, by 37% and 17% lower DON, and 27% and 32% lower D3G, respectively. BM treated with both P. oligandrum strains exhibited quality enhancement; beer produced from the BM treated with P. oligandrum strain M1 resulted in no quality deterioration and with 26% and 18% less DON and D3G, respectively, transferred to the final product.
This study examines the use of Pythium oligandrum as a biological control agent to suppress Fusarium culmorum growth and mycotoxin production during the malting of wheat (Triticum aestivum L.). The ...optimum application phase and dose of P. oligandrum were studied. The effect of P. oligandrum on F. culmorum-infected wheat was quantitatively evaluated through RT-PCR along with deoxynivalenol (DON) and deoxynivalenol-3-glucoside (D3G) content in wheat malt (WM). In addition, the effect of P. oligandrum treatment on WM quality was quantified by European Brewery Convention standard methods. Treatment by P. oligandrum in the steeping stage (2 g P. oligandrum/kg wheat) yielded optimal suppression of Fusarium contamination (20%) and mycotoxin content (17% DON and 21% D3G) relative to untreated WM. Treatment dose showed a maximum effect between 0.6 and 1 g P. oligandrum/kg of wheat, resulting in 12–14% Fusarium contamination, 13–14% DON, and 15–18% D3G, relative to untreated malt. Wheat malts treated with P. oligandrum showed no deterioration of malting or brewing quality.
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•Biological control of fungal contamination in malting is desirable.•Pythium oligandrum was used to combat Fusarium culmorum in infected wheat.•P. oligandrum was effective against fungal growth and mycotoxin production.•Optimum application (steeping) and dose (0.6–1 g/kg wheat) were established.•The brewing quality of wheat malt was not affected by P. oligandrum.
This study investigates the potential of Pythium oligandrum (strains M1 and 00X48) as a biocontrol agent in suppressing the growth of Fusarium culmorum and the production of mycotoxins during the ...malting of naturally contaminated barley (Hordeum vulgare). The effects of the biocontrol agent on F. culmorum-infected barley malt (BM) were evaluated through real-time PCR and its impact on mycotoxin production was determined by quantitative analysis of deoxynivalenol (DON) and deoxynivalenol-3-glucoside (D3G). The effect of treatment on BM and beer quality were also determined through European Brewery Convention (EBC) standard methods. Optimal treatment with P. oligandrum strains M1 and 00X48 yielded a 59% and 48% reduction in F. culmorum contamination, by 37% and 17% lower DON, and 27% and 32% lower D3G, respectively. BM treated with both P. oligandrum strains exhibited quality enhancement; beer produced from the BM treated with P. oligandrum strain M1 resulted in no quality deterioration and with 26% and 18% less DON and D3G, respectively, transferred to the final product.
Traditionally viewed as poorly plastic, neutrophils are now recognized as functionally diverse; however, the extent and determinants of neutrophil heterogeneity in humans remain unclear. We performed ...a comprehensive immunophenotypic and transcriptome analysis, at a bulk and single-cell level, of neutrophils from healthy donors and patients undergoing stress myelopoiesis upon exposure to growth factors, transplantation of hematopoietic stem cells (HSC-T), development of pancreatic cancer and viral infection. We uncover an extreme diversity of human neutrophils in vivo, reflecting the rates of cell mobilization, differentiation and exposure to environmental signals. Integrated control of developmental and inducible transcriptional programs linked flexible granulopoietic outputs with elicitation of stimulus-specific functional responses. In this context, we detected an acute interferon (IFN) response in the blood of patients receiving HSC-T that was mirrored by marked upregulation of IFN-stimulated genes in neutrophils but not in monocytes. Systematic characterization of human neutrophil plasticity may uncover clinically relevant biomarkers and support the development of diagnostic and therapeutic tools.
Titin-truncating variants (TTNtv) commonly cause dilated cardiomyopathy (DCM). TTNtv are also encountered in ∼1% of the general population, where they may be silent, perhaps reflecting allelic ...factors. To better understand TTNtv, we integrated TTN allelic series, cardiac imaging and genomic data in humans and studied rat models with disparate TTNtv. In patients with DCM, TTNtv throughout titin were significantly associated with DCM. Ribosomal profiling in rat showed the translational footprint of premature stop codons in Ttn, TTNtv-position-independent nonsense-mediated degradation of the mutant allele and a signature of perturbed cardiac metabolism. Heart physiology in rats with TTNtv was unremarkable at baseline but became impaired during cardiac stress. In healthy humans, machine-learning-based analysis of high-resolution cardiac imaging showed TTNtv to be associated with eccentric cardiac remodeling. These data show that TTNtv have molecular and physiological effects on the heart across species, with a continuum of expressivity in health and disease.
Acute respiratory infections are a major cause of morbidity and mortality in children worldwide. Dietary and nutritional interventions, including minerals and vitamin supplementation, have been ...explored as potential treatments for these infections. However, the evidence on their efficacy is limited and inconclusive. This systematic review and meta‐analysis aim to provide a comprehensive summary of the available evidence on the effectiveness of dietary and nutritional interventions for treating acute respiratory tract infections in children. A systematic review was conducted according to the PRISMA 2020 guidelines in April 2022 and updated in April 2023. Clinical trials focusing on dietary or nutritional interventions, including supplementations, in children with acute respiratory tract infections were included. The selection of interventions and outcomes was based on biological plausibility. Data were extracted using a standardized form, and the risk of bias was assessed using the Cochrane Risk of Bias Tool. Meta‐analysis was performed using random‐effect models. A total of 50 studies were included in the review. Four trials were conducted in low, 32 in lower‐middle, 12 in upper‐middle, and only two in high‐income countries. The studies evaluated various dietary interventions, including zinc, vitamin A, vitamin E, vitamin D, and probiotics. The results of individual studies on the efficacy of these interventions were mixed, with some showing positive effects on clinical outcomes such as duration of symptoms, while others showed no significant impact. Meta‐analysis was conducted for zinc supplementation in children with pneumonia, and the pooled results suggested a potential limited benefit in terms of reduced hospital length of stay but not time to recovery. Meta‐analyses on vitamin D did not show any effect in children with pneumonia. This systematic review fills a critical gap in the literature by synthesizing the available evidence on the efficacy and safety of nutritional or dietary interventions for acute respiratory tract infections in children. The findings indicate no dietary or nutritional intervention can currently be recommended for the routine treatment of respiratory tract infections in children based on single supplement studies. The metanalysis suggests that zinc supplementation might have a beneficial effect on length of hospitalization in children with pneumonia. New studies are needed to establish more conclusive evidence for pediatric acute respiratory diseases especially for children living in a context of high‐income countries.
Introduction
A non-interventional, multicenter, European, prospective evaluation of the effectiveness, tolerability, and safety of a topical preservative-free tafluprost (0.0015%) and timolol (0.5%) ...fixed-dose combination (PF tafluprost/timolol FC) in adults with open-angle glaucoma (OAG) and ocular hypertension (OHT) demonstrating insufficient response to topical beta-receptor blockers or prostaglandin analogue (PGA) monotherapy.
Methods
Mean intraocular pressure (IOP) change from baseline was measured at study visits following a switch to PF tafluprost/timolol FC. Primary endpoint was absolute mean IOP change at month 6. Change from baseline concerning ocular signs and symptoms was also explored.
Results
Analyses included 577 patients (59.6% female). Mean age (SD) was 67.8 (11.67) years. Mean (SD) IOP reduction from baseline was significant at all study visits; 5.4 (3.76) mmHg (23.7%) at week 4, 5.9 (3.90) mmHg (25.6%) at week 12, and 5.7 (4.11) mmHg (24.9%) at month 6 (
p
< 0.0001 for all visits). At month 6, 69.2%, 53.6%, 40.0%, and 25.8% were responders based on ≥ 20%, ≥ 25%, ≥ 30%, and ≥ 35% cutoff values for mean IOP, respectively. Significant reductions were observed concerning corneal fluorescein staining (
p
< 0.0001), dry eye symptoms, irritation, itching, and foreign body sensation (
p
< 0.001 for each parameter). Conjunctival hyperemia was significantly reduced at all study visits (
p
< 0.0001 at each visit). Overall, 69 treatment-related adverse events (AEs) were reported, one of which was serious (status asthmaticus). Most AEs were mild to moderate in severity, and the majority had resolved or were resolving at the end of the study period.
Conclusion
In clinical practice, PF tafluprost/timolol FC provided statistically and clinically significant IOP reductions in patients with OAG and OHT insufficiently controlled on or intolerant to PGA or beta-receptor blocker monotherapy. The full IOP reduction appeared at week 4 and was maintained over the 6-month study period. Key symptoms of ocular surface health improved.
Trial Registration
European Union electronic Register of Post-Authorisation Studies (EU PAS) register number, EUPAS22204.
Introduction
The VISIONARY study demonstrated statistically significant intraocular pressure (IOP) reductions with the preservative-free fixed-dose combination of tafluprost 0.0015% and timolol 0.5% ...(PF tafluprost/timolol FC) in open-angle glaucoma (OAG) or ocular hypertension (OHT) patients, sub-optimally controlled with topical prostaglandin analogue (PGA) or beta-blocker monotherapy. Current subanalyses have examined these data according to the baseline monotherapy.
Methods
A European, prospective, observational study included adults (aged ≥ 18 years) with OAG or OHT, who were switched to the PF tafluprost/timolol FC from PGA or beta-blocker monotherapy. Treatment outcomes were reported according to prior monotherapy subgroup: beta-blocker, preserved latanoprost, PF-latanoprost, bimatoprost, tafluprost, and travoprost. Endpoints included the mean change from baseline regarding IOP, conjunctival hyperemia, and corneal fluorescein staining (CFS) at Week 4 and Week 12, and at Month 6.
Results
The subanalysis included 577 patients. All prior monotherapy subgroups demonstrated statistically significant IOP reductions from baseline at Week 4, that were maintained through Month 6 (
p
< 0.001). Mean (SD) IOP change at Month 6 was 6.6 (4.16), 6.3 (4.39), 5.6 (3.67), 4.9 (2.97), 4.6 (4.39), and 4.7 (3.64) mmHg for prior beta-blocker, preserved latanoprost, PF-latanoprost, tafluprost, bimatoprost, and travoprost subgroups, respectively. The largest IOP change was observed in the preserved latanoprost subgroup for each of the ≥ 20%, ≥ 25%, ≥ 30%, and ≥ 35% IOP reduction categories at Month 6, demonstrating respective reductions of 8.06, 9.20, 10.64, and 11.55 mmHg. CFS was significantly reduced at Month 6 in the prior bimatoprost subgroup (
p
= 0.0013). Conjunctival hyperemia severity was significantly reduced at each study visit for prior preserved latanoprost users (
p
< 0.001).
Conclusion
PF tafluprost/timolol FC therapy provided statistically and clinically significant IOP reductions from Week 4 over the total 6-month period, in patients with OAG/OHT, regardless of the type of prior PGA or beta-blocker monotherapy used. Conjunctival hyperemia severity and CFS decreased significantly in prior bimatoprost and preserved latanoprost users, respectively.
Clinical Study Number
European Union electronic Register of Post-Authorization Studies (EU PAS) register number: EUPAS22204.
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