Improving strawberry plant resilience to salinity and alkalinity through the use of diverse spectra of supplemental lighting.

BACKGROUND: This study explores the impact of various light spectra on the photosynthetic performance of strawberry plants subjected to salinity, alkalinity, and combined salinity/alkalinity stress. We employed supplemental lighting through Light-emitting Diodes (LEDs) with specific wavelengths: monochromatic blue (460 nm), monochromatic red (660 nm), dichromatic blue/red (1:3 ratio), and white/yellow (400-700 nm), all at an intensity of 200 µmol m-2 S-1. Additionally, a control group (ambient light) without LED treatment was included in the study. The tested experimental variants were: optimal growth conditions (control), alkalinity (40 mM NaHCO3), salinity (80 mM NaCl), and a combination of salinity/alkalinity. RESULTS: The results revealed a notable decrease in photosynthetic efficiency under both salinity and alkalinity stresses, especially when these stresses were combined, in comparison to the no-stress condition. However, the application of supplemental lighting, particularly with the red and blue/red spectra, mitigated the adverse effects of stress. The imposed stress conditions had a detrimental impact on both gas exchange parameters and photosynthetic efficiency of the plants. In contrast, treatments involving blue, red, and blue/red light exhibited a beneficial effect on photosynthetic efficiency compared to other lighting conditions. Further analysis of JIP-test parameters confirmed that these specific light treatments significantly ameliorated the stress impacts. CONCLUSIONS: In summary, the utilization of blue, red, and blue/red light spectra has the potential to enhance plant resilience in the face of salinity and alkalinity stresses. This discovery presents a promising strategy for cultivating plants in anticipation of future challenging environmental conditions.

Correction: NGS read classification using AI.

[This corrects the article DOI: 10.1371/journal.pone.0261548.].

Amantadine in unvaccinated patients with early, mild to moderate COVID-19: A randomized, placebo-controlled, double-blind trial.

BACKGROUND AND PURPOSE: Adamantanes were listed as an interesting option as an early intervention against COVID-19. We aimed to evaluate the effectiveness of amantadine in preventing the progression of COVID-19 and its neurological sequelae. METHODS: Unvaccinated patients with confirmed SARS-CoV-2 infection within 5 days were enrolled. Subjects were randomized (50:50) to amantadine (AMD; 100 mg twice daily) or placebo (PLB) for 14 days. The Ordinal Scale for Clinical Improvement of the World Health Organization (OSCI-WHO) was the primary measure. Secondary endpoints included assessment for fatigue; depression, disorders of smell and taste, and sleepiness on Days 1 and 15. RESULTS: We enrolled 99 patients (49 AMD and 50 PLB). Disease progression (OSCI-WHO = 4) was observed in 6% (AMD) and 8% (PLB) patients (p > 0.05) with further deterioration (OSCI-WHO〉4) in 0% (AMD) and 8% (PLB) patients (p > 0.05). Complete recovery on Day 15 was 60% higher in the AMD compared with the PLB group (p = 0.025). There was improvement in taste (AMD: p = 0.003; PLB: p = 0.0001) and smell (AMD: p = 0.005; PLB: p = 0.0004) but not in fatigue in both groups. Improvement was observed in the AMD (p = 0.010) but not in the PLB group (p = 0.058) when assessing depression as well as sleepiness (AMD: p = 0.0002; PLB: p = 0.341). There was one death in the PLB group (2.0%) and none in the AMD group (p > 0.05) until Day 210. Overall, the drug was well tolerated. CONCLUSION: The central effects of amantadine on the nervous system with reduction of sleepiness and depression might have had a supportive effect on faster recovery in early COVID-19 patients.

Antimicrobial and Cytotoxic Activities of Water-Soluble Isoxazole-Linked 1,3,4-Oxadiazole with Delocalized Charge: In Vitro and In Vivo Results.

The distinct structure of cationic organic compounds plays a pivotal role in enhancing their water solubility, which in turn influences their bioavailability. A representative of these compounds, which contains a delocalized charge, is 5-amino-2-(5-amino-3-methyl-1,2-oxazol-4-yl)-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-ylium bromide (ED). The high-water solubility of ED obviates the need for potentially harmful solvents during in vitro testing. The antibacterial and antifungal activities of the ED compound were assessed in vitro using the microtiter plate method and a biocellulose-based biofilm model. Additionally, its cytotoxic effects on wound bed fibroblasts and keratinocytes were examined. The antistaphylococcal activity of ED was also evaluated using an in vivo larvae model of Galleria mellonella. Results indicated that ED was more effective against Gram-positive bacteria than Gram-negative ones, exhibiting bactericidal properties. Furthermore, ED demonstrated greater efficacy against biofilms formed by Gram-positive bacteria. At bactericidal concentrations, ED was non-cytotoxic to fibroblasts and keratinocytes. In in vivo tests, ED was non-toxic to the larvae. When co-injected with a high load of S. aureus, it reduced the average larval mortality by approximately 40%. These findings suggest that ED holds promise for further evaluation as a potential treatment for biofilm-based wound infections, especially those caused by Gram-positive pathogens like S. aureus.

Fungal symbionts impact cyanobacterial biofilm durability and photosynthetic efficiency.

Cyanobacteria contribute to over 25% of the world's net primary photosynthetic production and are pivotal in mitigating greenhouse gas emissions.1 This study unveils a previously unobserved symbiotic relationship between benthic cyanobacteria and fungi that have also adapted to life as a plant endophyte. The interaction suggests an initial phase of lichenization. We isolated Leptolyngbya frigida from the Naracauli stream, which emanates from abandoned Zn industrial waste in Sardinia. Seasonally, L. frigida participates in a biomineralization processes, mitigating the Zn transfer to rivers and, subsequently, the sea.2,3,4L. frigida is a benthic cyanobacterium that establishes a biofilm on the stream bed. Notably, the area predominantly features Juncus acutus. From these roots, endophytic fungi were predominantly isolated as Clonostachys rosea, a fungus recognized for its biocontrol capabilities against plant pathogens. An intriguing observation was made when L. frigida was cultured with C. rosea on a low-carbohydrate agar medium: the fungal mycelium transformed into wall-less forms, a phenomenon not documented previously. In liquid environments, the resulting biofilm first settled at the container's bottom. Even upon rising to the surface, this biofilm remained pigment rich. Concurrently, a secondary biofilm began its formation at the bottom. These fungal-integrated biofilms displayed enhanced resilience and superior photosynthetic performance compared to those without fungal presence. Moreover, the symbiotic relationship significantly amplified O2 emission and CO2 sequestration by the biofilm.

Effect of Neonatal Hearing Screening Results on the Lost to Follow-Up at the Diagnostic Level.

(1) Background: An important part of any neonatal hearing screening program is monitoring diagnostic visits to confirm or exclude the presence of hearing loss. In addition, time plays an important role in the diagnosis. We identified the number of children who came for a diagnostic visit and analyzed the time of the first audiological visit, depending on the result of the hearing screening test performed in the first days of a child's life and the presence or absence of risk factors of hearing impairment. (2) Methods: We analyzed 6,580,524 children, of which 8.9% required further diagnostics. The mean time of follow-up diagnostic visit in the analyzed group was 130 days and differed due to the presence or absence of risk factors for hearing loss before and after the neonatal period. (3) Results: Although the risk of hearing loss in children with risk factors is 2.31 to 6.38 times higher than in children without risk factors depending on the result of the screening test, more than 40% of parents do not report to scheduled audiological visits. (4) Conclusions: Doctors, nurses, and midwives who screen hearing at the neonatological level play an important role in educating parents about the possibility of hearing loss in a child and the need for an audiological examination.

Photosynthetic efficiency of perennial ryegrass (Lolium perenne L.) seedlings in response to Ni and Cd stress.

Perennial ryegrass is a grass species used to establish lawns in urban areas where pollution is a major environmental problems. Cadmium (Cd) and nickel (Ni) contribute significantly to these pollutants and may cause photosynthetic limitation. The main objective of this work was to perform a comprehensive analysis of photosynthetic efficiency of perennial ryegrass seedlings under Cd and Ni stress. Some of the main indices of photosynthetic efficiency (prompt and delayed chlorophyll-a fluorescence signals and modulated reflectance at 820 nm) were compared with growth parameters. Two cultivars were tested: 'Niga' and 'Nira'. A decrease in photosystem (PS) II and PSI activity was observed. This was due to an increase in nonradiative dissipation of the PSII antenna, a decrease in PSII antenna size, or a decrease in the number of photosynthetic complexes with fully closed PSII RCs. Efficiency of electron transport was decreased. The effect on the modulated reflectance signal could indicate a restriction in electron flow from PSII to PSI. The correlation between photosynthetic efficiency parameters, such as Area, Fo, Fm, and Fv, and growth parameters, confirmed that some photosynthetic efficiency parameters can be used as indicators for early detection of heavy metal effects.

The impact of the COVID 19 pandemic on the functioning of the Universal Newborn Hearing Screening Program in Poland.

The Newborn Hearing Screening Program has existed in Poland for almost 20 years. However, for the first time in the history of his activity, he had to deal with large logistic and staffing problems. The analysis compared the years 2020 and 2021 in terms of the functioning of centers that conduct audiological diagnostics of the Program during the Covid-19 pandemic. In order to obtain relevant information, a telephone survey was conducted at the beginning of 2022 with questions about the performance of standard activities related to the Program. Results In 2020, 60 centers conducting audiological diagnostics (66.67%) were suspended, and 30 were working under the sanitary and epidemiological regime (33.33%). In 2021, only 5 (5.26%) diagnostic centers with their headquarters in facilities transformed into so-called homonymous hospitals, dealing only with the treatment of patients infected with SARS-CoV-2 virus, were suspended. Discussion The development of the pandemic and the related limitations around the world had a significant impact on the quality and scope of medical services provided. Many hospitals were quickly transformed into closed centers treating only patients with SARS-CoV-2. Audiological consultations take place in closed, soundproof rooms. Face-to-face contact was required for hearing assessment, fitting hearing aids, troubleshooting, and rehabilitation. The COVID-19 pandemic has forced audiology to modify existing practices. The use of telemedicine was increasingly preferred. In Poland, as all over the world, the scope of remote consultations has expanded, but due to technological and hardware limitations, audiological procedures remained in the sphere of direct contact with the patient. Conclusions In the first year after the announcement of the pandemic, significant difficulties were observed in the functioning of centers dealing with the diagnosis of children with suspected hearing loss. The appearance of the SARS-CoV-2 virus forced us to develop innovative methods of early diagnosis and treatment of children with hearing impairment, which resulted in the stabilization of the work of individuals in the following year.

PathoLive-Real-Time Pathogen Identification from Metagenomic Illumina Datasets.

Over the past years, NGS has become a crucial workhorse for open-view pathogen diagnostics. Yet, long turnaround times result from using massively parallel high-throughput technologies as the analysis can only be performed after sequencing has finished. The interpretation of results can further be challenged by contaminations, clinically irrelevant sequences, and the sheer amount and complexity of the data. We implemented PathoLive, a real-time diagnostics pipeline for the detection of pathogens from clinical samples hours before sequencing has finished. Based on real-time alignment with HiLive2, mappings are scored with respect to common contaminations, low-entropy areas, and sequences of widespread, non-pathogenic organisms. The results are visualized using an interactive taxonomic tree that provides an easily interpretable overview of the relevance of hits. For a human plasma sample that was spiked in vitro with six pathogenic viruses, all agents were clearly detected after only 40 of 200 sequencing cycles. For a real-world sample from Sudan, the results correctly indicated the presence of Crimean-Congo hemorrhagic fever virus. In a second real-world dataset from the 2019 SARS-CoV-2 outbreak in Wuhan, we found the presence of a SARS coronavirus as the most relevant hit without the novel virus reference genome being included in the database. For all samples, clinically irrelevant hits were correctly de-emphasized. Our approach is valuable to obtain fast and accurate NGS-based pathogen identifications and correctly prioritize and visualize them based on their clinical significance: PathoLive is open source and available on GitLab and BioConda.

The effect of supplementary light on the photosynthetic apparatus of strawberry plants under salinity and alkalinity stress.

Considering the destructive effect of stresses on the photosynthetic apparatus of plants and the important role of light in photosynthesis, we investigated the effect of complementary light on the photosynthetic apparatus under salinity and alkalinity stress conditions. Light-emitting diodes (LEDs) in monochromatic blue (460 nm), monochromatic red (660 nm), dichromatic blue/red (1:3), white/yellow (400-700 nm) at 200 µmol m-2 S-1, and without LED treatment were used. The stress treatments were in three stages: Control (no stress), Alkalinity (40 mM NaHCO3), and Salinity (80 mM NaCl). Our results showed that salinity and alkaline stress reduced CO2 assimilation by 62.64% and 40.81%, respectively, compared to the control treatment. The blue light spectrum had the highest increase in water use efficiency (54%) compared to the treatment without supplementary light. Under salinity and alkalinity stress, L, K, and H bands increased and G bands decreased compared to the control treatment, with blue/red light causing the highest increase in L and K bands under both stress conditions. In salinity and alkalinity stress, white/yellow and blue/red spectra caused the highest increase in H bands. Complementary light spectra increased the G band compared to the treatment without complementary light. There was a significant decrease in power indices and quantum power parameters due to salt and alkalinity stress. The use of light spectra, especially blue, red, and blue/red light, increased these parameters compared with treatment without complementary light. Different light spectra have different effects on the photosynthetic apparatus of plants. It can be concluded that using red, blue spectra and their combination can increase the resistance of plants to stress conditions and be adopted as a strategy in planting plants under stress conditions.

Supplemental light application can improve the growth and development of strawberry plants under salinity and alkalinity stress conditions.

The use of complementary light spectra is a potential new approach to studying the increase in plant resilience under stress conditions. The purpose of this experiment was to investigate the effect of different spectra of complementary light on the growth and development of strawberry plants under salinity and alkalinity stress conditions. Plants were grown in the greenhouse under ambient light and irradiated with blue (460 nm), red (660 nm), blue/red (1:3), and white/yellow (400-700 nm) light during the developmental stages. The stress treatments were as follows: control (non-stress), alkalinity (40 mM NaHCO3), and salinity (80 mM NaCl). Our results showed that salinity and alkalinity stress decreased fresh and dry weights and the number of green leaves, and increased chlorotic, tip burn, and dry leaves. The blue and red spectra had a greater effect on reducing the effects of stress compared to other spectra. Stress conditions decreased SPAD and RWC, although blue light increased SPAD, and blue/red light increased RWC under stress conditions. Blue/red and white/yellow light had the greatest effect on reproductive traits. Stress conditions affected fruit color indicators, and red and blue light had the most significant effect on these traits. Under stress conditions, sodium uptake increased, while K, Ca, Mg, and Fe uptake decreased, markedly. Blue and red light and their combination alleviated this reducing effect of stress. It can be concluded that the effects of salinity and alkalinity stresses can be reduced by manipulating the supplemental light spectrum. The use of artificial light can be extended to stresses.

Deacclimation-Induced Changes of Photosynthetic Efficiency, Brassinosteroid Homeostasis and BRI1 Expression in Winter Oilseed Rape (Brassica napus L.)-Relation to Frost Tolerance.

The objective of this study was to answer the question of how the deacclimation process affects frost tolerance, photosynthetic efficiency, brassinosteroid (BR) homeostasis and BRI1 expression of winter oilseed rape. A comparative study was conducted on cultivars with different agronomic and physiological traits. The deacclimation process can occur when there are periods of higher temperatures, particularly in the late autumn or winter. This interrupts the process of the acclimation (hardening) of winter crops to low temperatures, thus reducing their frost tolerance and becoming a serious problem for agriculture. The experimental model included plants that were non-acclimated, cold acclimated (at 4 °C) and deacclimated (at 16 °C/9 °C, one week). We found that deacclimation tolerance (maintaining a high frost tolerance despite warm deacclimating periods) was a cultivar-dependent trait. Some of the cultivars developed a high frost tolerance after cold acclimation and maintained it after deacclimation. However, there were also cultivars that had a high frost tolerance after cold acclimation but lost some of it after deacclimation (the cultivars that were more susceptible to deacclimation). Deacclimation reversed the changes in the photosystem efficiency that had been induced by cold acclimation, and therefore, measuring the different signals associated with photosynthetic efficiency (based on prompt and delayed chlorophyll fluorescence) of plants could be a sensitive tool for monitoring the deacclimation process (and possible changes in frost tolerance) in oilseed rape. Higher levels of BR were characteristic of the better frost-tolerant cultivars in both the cold-acclimated and deacclimated plants. The relative expression of the BRI1 transcript (encoding the BR-receptor protein) was lower after cold acclimation and remained low in the more frost-tolerant cultivars after deacclimation. The role of brassinosteroids in oilseed rape acclimation/deacclimation is briefly discussed.

The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design.

BACKGROUND: COVID-19, a disease caused by infection with the SARS-CoV-2 virus, is asymptomatic or mildly symptomatic in most cases. Some patients, usually burdened with risk factors develop acute respiratory failure and other organ dysfunction. In such cases, the mortality rate is very high despite the use of intensive therapy. Amantadine has complex activity including antiviral, antiinflammatory and dopaminergic effects. This clinical trial will assess the efficacy and safety of amantadine in the prevention of COVID-19 progression toward acute respiratory failure and neurological complications. METHODS AND RESULTS: The trial will enroll 200 patients who are positive for SARS-CoV-2 infection and have one or more risk factors for worsening the disease. These patients will be included as hospitalized or ambulatory subjects for early treatment of illness. The recruitment will take place in 8 centers covering different regions of Poland. For 14 days they will be given either 200 mg of amantadine a day or placebo. Our hypothesis is a considerable reduction in the number of patients with progression toward respiratory insufficiency or neurological complications thanks to the treatment of amantadine. CONCLUSIONS: Demonstrating the efficacy and safety of amantadine treatment in improving the clinical condition of patients diagnosed with COVID-19 is of great importance in combating the effects of the pandemic. It has potential to influence on the severity and course of neurological complications, which are very common and persist long after the infection as long-COVID syndrome. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov identification no. NCT04854759; Eudra CT number: 2021-001144-98 (dated 27 February 2021).

Critical Assessment of Metagenome Interpretation: the second round of challenges.

Evaluating metagenomic software is key for optimizing metagenome interpretation and focus of the Initiative for the Critical Assessment of Metagenome Interpretation (CAMI). The CAMI II challenge engaged the community to assess methods on realistic and complex datasets with long- and short-read sequences, created computationally from around 1,700 new and known genomes, as well as 600 new plasmids and viruses. Here we analyze 5,002 results by 76 program versions. Substantial improvements were seen in assembly, some due to long-read data. Related strains still were challenging for assembly and genome recovery through binning, as was assembly quality for the latter. Profilers markedly matured, with taxon profilers and binners excelling at higher bacterial ranks, but underperforming for viruses and Archaea. Clinical pathogen detection results revealed a need to improve reproducibility. Runtime and memory usage analyses identified efficient programs, including top performers with other metrics. The results identify challenges and guide researchers in selecting methods for analyses.

Summary of the Polish Universal Neonatal Hearing Screening Program 2021year review.

The Polish Universal Neonatal Hearing Screening Program (PUNHSP) has been carried out in Poland for 20 years. Its main goal is to screen newborns for hearing. This examination is performed on the 2-3 days of a child's life, and in addition, information is collected on the risk factors for the development of hearing loss. In total, 486 centers participate in PPPBSuN at three reference levels. By the end of 2021, 7 million children were registered in the PPPBSuN Central Database. The most common type of hearing loss in children was bilateral sensorineural hearing loss, diagnosed in 2021 in 160 children. The report below presents the most important results and conclusions from the functioning of PPPBSuN in 2021.

Manipulation of light spectrum can improve the performance of photosynthetic apparatus of strawberry plants growing under salt and alkalinity stress.

Strawberry is one of the plants sensitive to salt and alkalinity stress. Light quality affects plant growth and metabolic activities. However, there is no clear answer in the literature on how light can improve the performance of the photosynthetic apparatus of this species under salt and alkalinity stress. The aim of this work was to investigate the effects of different spectra of supplemental light on strawberry (cv. Camarosa) under salt and alkalinity stress conditions. Light spectra of blue (with peak 460 nm), red (with peak 660 nm), blue/red (1:3), white/yellow (1:1) (400-700 nm) and ambient light were used as control. There were three stress treatments: control (no stress), alkalinity (40 mM NaHCO3), and salinity (80 mM NaCl). Under stress conditions, red and red/blue light had a positive effect on CO2 assimilation. In addition, blue/red light increased intrinsic water use efficiency (WUEi) under both stress conditions. Salinity and alkalinity stress decreased OJIP curves compared to the control treatment. Blue light caused an increase in its in plants under salinity stress, and red and blue/red light caused an increase in its in plants under alkalinity. Both salt and alkalinity stress caused a significant reduction in photosystem II (PSII) performance indices and quantum yield parameters. Adjustment of light spectra, especially red light, increased these parameters. It can be concluded that the adverse effects of salt and alkalinity stress on photosynthesis can be partially alleviated by changing the light spectra.

NGS read classification using AI.

Clinical metagenomics is a powerful diagnostic tool, as it offers an open view into all DNA in a patient's sample. This allows the detection of pathogens that would slip through the cracks of classical specific assays. However, due to this unspecific nature of metagenomic sequencing, a huge amount of unspecific data is generated during the sequencing itself and the diagnosis only takes place at the data analysis stage where relevant sequences are filtered out. Typically, this is done by comparison to reference databases. While this approach has been optimized over the past years and works well to detect pathogens that are represented in the used databases, a common challenge in analysing a metagenomic patient sample arises when no pathogen sequences are found: How to determine whether truly no evidence of a pathogen is present in the data or whether the pathogen's genome is simply absent from the database and the sequences in the dataset could thus not be classified? Here, we present a novel approach to this problem of detecting novel pathogens in metagenomic datasets by classifying the (segments of) proteins encoded by the sequences in the datasets. We train a neural network on the sequences of coding sequences, labeled by taxonomic domain, and use this neural network to predict the taxonomic classification of sequences that can not be classified by comparison to a reference database, thus facilitating the detection of potential novel pathogens.

The virome of German bats: comparing virus discovery approaches.

Bats are known to be reservoirs of several highly pathogenic viruses. Hence, the interest in bat virus discovery has been increasing rapidly over the last decade. So far, most studies have focused on a single type of virus detection method, either PCR, virus isolation or virome sequencing. Here we present a comprehensive approach in virus discovery, using all three discovery methods on samples from the same bats. By family-specific PCR screening we found sequences of paramyxoviruses, adenoviruses, herpesviruses and one coronavirus. By cell culture we isolated a novel bat adenovirus and bat orthoreovirus. Virome sequencing revealed viral sequences of ten different virus families and orders: three bat nairoviruses, three phenuiviruses, one orbivirus, one rotavirus, one orthoreovirus, one mononegavirus, five parvoviruses, seven picornaviruses, three retroviruses, one totivirus and two thymoviruses were discovered. Of all viruses identified by family-specific PCR in the original samples, none was found by metagenomic sequencing. Vice versa, none of the viruses found by the metagenomic virome approach was detected by family-specific PCRs targeting the same family. The discrepancy of detected viruses by different detection approaches suggests that a combined approach using different detection methods is necessary for virus discovery studies.

First detection of bat-borne Issyk-Kul virus in Europe.

Bats have been gaining attention as potential reservoir hosts of numerous viruses pathogenic to animals and man. Issyk-Kul virus, a member of the family Nairoviridae, was first isolated in the 1970s from vespertilionid bats in Central Asia. Issyk-Kul virus has been described as human-pathogenic virus, causing febrile outbreaks in humans with headaches, myalgia and nausea. Here we describe the detection of a novel strain of Issyk-Kul virus from Eptesicus nilssonii in Germany. This finding indicates for the first time the prevalence of these zoonotic viruses in Europe.

Trimebutine Maleate Monotherapy for Functional Dyspepsia: A Multicenter, Randomized, Double-Blind Placebo Controlled Prospective Trial.

Background and Objectives: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders; it has a great impact on patient quality of life and is difficult to treat satisfactorily. This study evaluates the efficacy and safety of trimebutine maleate (TM) in patients with FD. Materials and Methods: Α multicenter, randomized, double-blind, placebo controlled, prospective study was conducted, including 211 patients with FD. Participants were randomized to receive TM 300 mg twice per day (BID, 108 patients) or placebo BID (103 patients) for 4 weeks. The Glasgow Dyspepsia Severity Score (GDSS) was used to evaluate the relief of dyspepsia symptoms. Moreover, as a pilot secondary endpoint, a substudy (eight participants on TM and eight on placebo) was conducted in to evaluate gastric emptying (GE), estimated using a 99mTc-Tin Colloid Semi Solid Meal Scintigraphy test. Results: Of the 211 patients enrolled, 185 (87.7%) (97 (52.4%) in the TM group and 88 (47.6%) in the placebo group) completed the study and were analyzed. The groups did not differ in their demographic and medical history data. Regarding symptom relief, being the primary endpoint, a statistically significant reduction in GDSS for the TM group was revealed between the first (2-week) and final (4-week) visit (p-value = 0.02). The 99 mTc-Tin Colloid Semi Solid Meal Scintigraphy testing showed that TM significantly accelerated GE obtained at 50 min (median emptying 75.5% in the TM group vs. 66.6% in the placebo group, p = 0.036). Adverse effects of low to moderate severity were reported in 12.3% of the patients on TM. Conclusion: TM monotherapy appears to be an effective and safe approach to treating FD, although the findings presented here warrant further confirmation.